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Souza, Paulo Fernando Araujo de. "The effects of dietary fat on the metabolism of the lactating rat." Thesis, University of Oxford, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.276817.
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Stahl, Richard J. (Richard John). "Fatty acid and glycerolipid biosynthesis in pea root plastids." Thesis, McGill University, 1990. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=22389.
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Fatty acid biosynthesis from (1-$ sp{14}$C) acetate was optimized in plastids isolated from primary root tips of 7-day-old germinating pea seeds. Fatty acid synthesis was maximum at 82.3 nmol/hr/mg protein in the presence of 200$ mu$M acetate, 0.5mM each of NADH, NADPH and CoA, 6mM each of ATP and MgCl$ sb2$, 1mM each of MnCl$ sb2$ and glycerol-3-phosphate (G3P), 15mM KHCO$ sb3$, and 0.1M Bis tris propane, pH 8.0 incubated at 35C. At the standard incubation temperature of 25C, fatty acid synthesis was linear for up to 6 hours with 80 to 120 $ mu$g/ml plastid protein. ATP and CoA were absolute requirements, whereas divalent cations, potassium bicarbonate and reduced nucelotides all improved activity by 2 to 10 fold. Mg$ sp{2+}$ and NADH were the preferred cation and nucleotide, respectively. G3P and dihydroxyacetone phosphate had little effect, and dithiothreitol and detergents generally inhibited incorporation of $ sp{14}$C-acetate into fatty acid.Glycerolipid synthesis was obtained from $ sp{14}$C-acetate, (U-$ sp{14}$C) G3P and (U-$ sp{14}$C) glycerol at relative rates of 3.7:1.0:0.1, respectively. (Abstract shortened by UMI.)
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Qi, Qungang. "The role of glycolytic metabolism in fatty acid and glycerolipid biosynthesis in pea root plastids." Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=39980.
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The interaction between the glycolytic metabolism and fatty acid and glycerolipid biosynthesis in pea root (Pisum sativum L.) plastids was assessed in this study. When various glycolytic intermediates were used to substitute for the APT requirement for fatty acid synthesis from acetate, phosphoenolpyruvate, 2-phosphoglycerate, fructose-6-phosphate and glucose-6-phosphate each gave 48, 17, 23 and 17%, respectively, of the ATP-control activity. Similarly, in the absence of exogenously supplied ATP, the optimized triose-phosphate shuttle, which consists of 2 mM dihydroxyacetone phosphate, 2 mM oxaloacetic acid and 4 mM inorganic phosphate, gave up to 44% the ATP-control activity in promoting fatty acid synthesis from acetate. These results suggest that 3-phosphoglycerate kinase and pyruvate kinase in these plastids can function in intraplastidic ATP production through substrate level phosphorylation. However, in all cases, exogenously supplied ATP gave the greatest rates of fatty acid and glycerolipid synthesis. Radiolabeled pyruvate, glucose, glucose-6-phosphate, and malate in comparison to acetate were all variously utilized for fatty acid and glycerolipid biosynthesis by the root plastid. At the highest concentrations tested (3-5 mM), the rates of incorporation of pyruvate, glucose-6-phosphate and acetate into fatty acids were 183, 154, 125 nd 99 nmol $ rm cdot h sp{-1} cdot mg sp{-1}$, respectively. Malate was the least effective precursor, giving less than 55 nmol $ rm cdot h sp{-1} cdot mg sp{-1}$. Acetate incorporation was approximately 55% dependent on exogenously supplied reduced nuclotides (NADPH and NADH), whereas the utilization of the remaining precursors was only approximately 10-20% dependent on NAD(P)H. These results indicate that the entire pathway of carbon flow from glycolysis, including pyruvate dehydrogenase (PDHase), to fatty acids is operating in pea root plastids. Further, the intraplastidic glycolytic pathway plays an important role in provi
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Behrman, Roger L. "The effects of dietary fat and age on adipose tissue composition and fatty acid synthesis levels in strain A/ST mice." Virtual Press, 1990. http://liblink.bsu.edu/uhtbin/catkey/722436.
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Differences in fatty acid distributions in adipose tissue and fatty acid synthetase levels in the liver were determined in Strain A/ST mice of different ages and diets. Since fatty acids have been found to be influential in many disease processes such as heart disease and cancer, which become more prevalent with increasing age, it is important to understand the processes of fat metabolism and changes that occur during the life-stage of senescence. Fatty acid distributions were determined by gas liquid chromatography and fatty acid synthetase (FAS) activities by spectrophotometry.The data from FAS analyses indicated that the mice fed the highfat palmitic acid and low-fat corn oil diets were similar to previous research. The mice fed the stearic acid diets had FAS activity that was affected in a very different manner than other high-fat diets.The results of this study also indicated that aging does not significantly effect the distribution of fatty acids in the adipose tissue of experimental mice. Weight gain in the middle age mice appears to be the result of an increase in all types of fatty acids and not just increased storage of one or a few types.Department of Biology
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Park, Young kyoung. "Metabolic engineering of the yeast Yarrowia lipolytica for the production of even- and odd-chain fatty acids." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASB010.
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Les huiles microbiennes sont considérées comme des alternatives prometteuses aux combustibles fossiles qui suscitent de plus en plus de préoccupations environnementales et énergétiques. Les acides gras à chaîne impaires (AGI), un type de lipide inhabituel, sont des composés d’intérêt ayant diverses applications biotechnologiques. L’objectif de cette thèse est de développer Yarrowia lipolytica comme souche plateforme, par l’ingénierie métabolique, pour la production d’AGI.Pour développer Y. lipolytca, l'identification et la caractérisation d’une nouvelle série de promoteurs érythritol-hybrides-inductible (pEYK1, pEYD1, et dérivés) ont été réalisées. La série de promoteurs hybrides a montré des forces variables, l'induction à base d'érythritol a augmenté de 2,2 à 32,3 fois dans la souche WT et de 2,9 à 896,1 fois dans la souche eyk1Δ. Ces promoteurs amélioreront la capacité de moduler l'expression de gènes chez Y. lipolytica.Pour la production d’AGI, la tolérance au propionate a été étudiée. Deux gènes, RTS1 et MFS1, améliorant la résistance au propionate ont été identifiés par le criblage d’une banque d’ADN génomique. Par des stratégies d’ingénierie métabolique, comme l’inhibition de la voie compétitive, l’augmentation les pools de précurseurs, et l’amélioration de l’accumulation de lipides totale, la production d'AGI a été augmentée de 0,14 g/L à 1,87 g/L. La production de novo des AGI sans supplémentation de propionate a également été explorée. Par surexpression des gènes dans la voie de synthèse de la thréonine, la production d’AGI été augmentée de 12 fois par rapport à la souche sauvage (0,36 versus 0,03 g/L).En résumé, des souches de Y. lipolytica ont été développées pour produire efficacement des AGI, principalement l’acide heptadécénoïque. Ce travail ouvre la voie à la production microbienne d'AGI et de ses dérivés à plus grande échelleMicrobial oils are regarded as promising alternatives to fossil fuels with growing environmental and energy concerns. Odd-chain fatty acids (OCFAs), a type of unusual lipids, are value-added compounds with various biotechnological applications. The objective of the thesis was to develop Yarrowia lipolytica as a platform strain for the production of OCFAs by metabolic engineering.For developing Y. lipolytica, the identification and characterization of a new series of erythritol-hybrid-inducible promoters (pEYK1, pEYD1, and derivatives) were explored. The hybrid promoter series showed variable strengths, erythritol-based induction increased 2.2 to 32.3 times in the WT strain and 2.9 to 896.1 times in the eyk1Δ strain, which will improve the modulation of gene expression for metabolic engineering of Y. lipolytica.For OCFA production, tolerance to propionate was studied. Two genes, RTS1 and MFS1, were identified as propionate-tolerant genes by screening a genomic DNA library. Through metabolic engineering strategies, such as inhibiting competitive pathways, increasing precursor pools, and enhancement of total lipid accumulation, OCFA production was increased from 0.14 g/L to 1.87 g/L. De novo production of OCFAs without propionate supplementation was also explored by overexpression of the threonine synthesis pathway. OCFAs production was increased by 12-times; 0.36 versus 0.03 g/L for WT.In summary, Y. lipolytica strains were developed to produce high-amount of OCFAs, mainly heptadecenoic acid. This work paves the way for the microbial production of OCFAs and their derivatives at the industrial scale
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Masterson, Christine. "Carnitine and fatty acid metabolism in higher plants." Thesis, University of Newcastle Upon Tyne, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.254030.
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Zampelas, Antonios. "Effect of dietary fatty acid structure and composition on postprandial lipid metabolism." Thesis, University of Surrey, 1993. http://epubs.surrey.ac.uk/770401/.
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In this thesis effects of dietary fatty acid composition and of positional distribution of fatty acids in dietary TAG, on postprandial lipid and hormone responses, were investigated. A6 week fish oil supplementation period (2.7 g n-3 fatty acids per day) decreased fasting TAG and increased TC (p<0.05) and LDL-C (p<0.05) levels in normal subjects. Postprandial plasma TAG responses to a test meal were also significantly reduced following the fish oil supplementation period (area under the response curves, p<0.001). Apolipoproteins A-I and B responses did not alter in response to chronic fish oil supplementation. Type II diabetics responded differently to normal subjects to fish oil supplementation. Fasting lipid and apolipoprotein levels were not significantly altered, and the postprandial TAG response to a test meal showed a trend towards higher values following the fish oil supplementation period. In the study of effects of dietary TAG structure on postprandial lipid apolipoprotein (A-I, B), hormone (insulin, GIP) and glucose responses, no effect of test meals differing in the positional distribution of palmitic acid at the sn-2 or the sn-3 positions of the TAG molecule were seen. In a study of acute effects of dietary fatty acid composition in healthy male subjects, a fish oil test meal (40 g fish oil concentrate), significantly reduced plasma TAG postprandial responses compared with a mixed oil meal (containing 40 g of a mixture of oils high in SFA and mimicking the current U. K. dietary fat intake), p<0.05. Post-heparin LPL activity was also significantly increased 12 hours following the fish oil test meal (p<0.01). A 40 g corn oil test meal did not have any significant effect on postprandial lipid, hormone (insulin and GIP), and retinyl palmitate levels (the latter was administered with each test meal-700 I. U. /kg of body weight) compared with the other two test meals. A feeding study, using a rat model, showed that following two weeks of a fish oil diet (5%, w/w) the postprandial incorporation of [U-t4C]glucose into hepatic total lipids and TAG measured in vitro, was significantly reduced compared with rates measured in animals on a mixed oil diet (p<0.05). In the presence of the two anabolic hormones, insulin and GIP, in vitro rates of hepatic cholesterogenesis increased (p<0.05), and these effects of hormones were independent of the type of the diet fed. In addition, plasma TAG levels were significantly lower in the fish oil group compared with levels in the mixed oil and corn oil dietary groups (p<0.05), and plasma insulin levels were significantly higher in the mixed oil dietary group than in the other two groups (p<0.001).
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Erol, Erdal. "Heart- and liver-type fatty acid binding proteins in lipid and glucose metabolism." Diss., Texas A&M University, 2004. http://hdl.handle.net/1969.1/1148.
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Heart-type Fatty Acid-Binding Protein (H-FABP) is required for high rates of skeletal muscle long chain fatty acid (LCFA) oxidation and esterification. Here we assessed whether H-FABP affects soleus muscle glucose uptake when measured in vitro in the absence of LCFA. Wild type and H-FABP null mice were fed a standard chow or high fat diet before muscle isolation. With the chow, the mutation increased insulin-dependent deoxyglucose uptake by 141% (P<0.01) at 0.02 mU/ml of insulin, but did not cause a significant effect at 2 mU/ml insulin; skeletal muscle triglyceride and long chain acyl-CoA (LCACoA) levels remained normal. With the fat diet, the mutation increased insulin-dependent deoxyglucose uptake by 190% (P<0.01) at 2 mU/ml insulin, thus partially preventing insulin resistance, and completely prevented the threefold (P<0.001) diet-induced increase of muscle triglyceride levels; however, muscle LCACoA levels showed little or no reduction. With both diets, the mutation reduced the basal (insulinindependent) soleus muscle deoxyglucose uptake by 28% (P<0.05). These results establish a close relationship of FABP-dependent lipid pools with insulin sensitivity, and indicate the existence of a non-acute, antagonistic, and H-FABP-dependent fatty acid regulation of basal and insulin-dependent muscle glucose uptake.
Liver fatty acid binding protein (L-FABP) has been proposed to limit the availability of chain LCFA for oxidation and for peroxisome proliferator-activated receptor (PPAR-alpha), a fatty acid binding transcription factor that determines the capacity of hepatic fatty acid oxidation. Here, we used L-FABP null mice to test this hypothesis. Under fasting conditions, this mutation reduced β-hydroxybutyrate (BHB) plasma levels as well as BHB release and palmitic acid oxidation by isolated hepatocytes. However, the capacity for ketogenesis was not reduced: BHB plasma levels were restored by octanoate injection; BHB production and palmitic acid oxidation were normal in liver homogenates; and hepatic expression of key PPAR-alpha target (MCAD, mitochondrial HMG CoA synthase, ACO, CYP4A3) and other (CPT1, LCAD) genes of mitochondrial and extramitochondrial LCFA oxidation and ketogenesis remained at wild-type levels. These results suggest that under fasting conditions, hepatic L-FABP contributes to hepatic LCFA oxidation and ketogenesis by a nontranscriptional mechanism.
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Jenkins, Benjamin John. "The role of alpha oxidation in lipid metabolism." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/278025.
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Recent findings have shown an inverse association between the circulating levels of pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) with the risk of pathological development in type 2 diabetes, cardio vascular disease and neurological disorders. From previously published research, it has been said that both these odd chain fatty acids are biomarkers of their dietary intake and are significantly correlated to dietary ruminant fat intake. However, there are profound studies that show the contrary where they do not display this biomarker correlation. Additionally, several astute studies have suggested or shown odd chain fatty acid endogenous biosynthesis, most often suggested via alpha oxidation; the cleavage of a single carbon unit from a fatty acid chain within the peroxisomes. To better understand the correlations and interactions between these two fatty acids with pathological development, the origin of these odd chain fatty acids needed to be determined, along with confirming their association with the disease aetiology. To minimise animal & human experimentation we made use of existing sample sets made available through institutional collaborations, which produced both animal and human interventional study samples suitable for odd chain fatty acid investigations. These sample collaborations allowed us to comprehensively investigate all plausible contributory sources of these odd chain fatty acids; including from the intestinal microbiota, from dietary contributions, and derived from novel endogenous biosynthesis. The investigations included two intestinal germ-free studies, two ruminant fat diet studies, two dietary fat studies and an ethanol intake study. Endogenous biosynthesis was assessed through: a stearic acid infusion, phytol supplementation, and an Hacl1 knockout mouse model. A human dietary intervention study was used to translate the results. Finally, a study comparing circulating baseline C15:0 and C17:0 levels with the development of glucose intolerance. We found that the circulating C15:0 and C17:0 levels were not significantly influenced by the presence or absence of intestinal microbiota. The circulating C15:0 levels were significantly and linearly increased when the C15:0 dietary composition increased; however, there was no significant correlation in the circulating C17:0 levels with intake. Circulating levels of C15:0 were affected by the dietary composition and factors affecting the dietary intake, e.g. total fat intake and ethanol, whereas circulating C17:0 levels were found to be independent of these variables. In our studies, the circulating C15:0 levels were not significantly affected by any expected variations in alpha oxidation caused by pathway substrate inhibition or gene knockout. However, C17:0 was significantly related, demonstrating it is substantially endogenously biosynthesised. Furthermore, we found that the circulating C15:0 levels, when independent of any dietary variations, did not correlate with the progression of glucose intolerance when induced, but the circulating C17:0 levels did significantly relate and linearly correlated with the development of glucose intolerance. To summarise, the circulating C15:0 and C17:0 levels were independently derived; the C15:0 levels substantially correlated with its dietary intake, whilst the C17:0 levels proved to be separately derived from its endogenous biosynthesis via alpha oxidation of stearic acid. C15:0 was found to be minimally endogenously biosynthesised via a single cycle of beta oxidation of C17:0 in the peroxisomes, however, this did not significantly contribute to the circulating levels of C15:0. Additionally, only the baseline levels of C17:0 significantly correlated with the development of glucose intolerance. These findings highlight the considerable differences between both of these odd chain fatty acids that were once thought to be homogeneous and similarly derived. On the contrary, they display profound dietary, metabolic, and pathological differences.
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Johnson, Philip E. "Interaction of subcellular compartments during lipid synthesis in oilseed rape (Brassica napus L.)." Thesis, University of East Anglia, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302211.
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Pratt, Vera Christine. "Essential fatty acid metabolism and immune function in disease states characterized by immunosuppression and abnormalities in lipid metabolism." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/NQ60335.pdf.
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Simoens, Christian. "Intravascular metabolism of lipid emulsions with different fatty acid pattern: influence on fatty acid profile of membrane phospholipids in target organs and cells." Doctoral thesis, Universite Libre de Bruxelles, 2011. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209776.
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Li, Hongping 1967. "Developmental relationships in the function of pea root plastids." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=30823.
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Germinating pea (Pisum sativum L.) roots were divided into five sequential 0.5 cm segments from the root tip. Pooled segments were analyzed for their protein, starch and lipid content as an indirect indication of plastid function. Fresh weights of root segments were lowest in the tips (4.45mug per segment) and progressively higher up to the fifth segment (11.09mug per segment). Total protein, starch and lipid content, on a per segment basis, were all highest in zone 1 (tip segment) and progressively lower up to zone 5. Plastids were isolated from each of the five root segments and analyzed for their capacity for lipid biosynthesis under several different in vitro conditions. Collectively, the observations presented here suggest that the relative contributions of plastids to the overall physiology of germinating pea roots gradually diminishes as root development proceeds, and that plastids isolated from progressively older root zones have increased capacity for glycolytic and/or pentose phosphate metabolism. (Abstract shortened by UMI.)
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Kiezel-Tsugunova, Magdalena. "Elucidating the metabolism of n-3 polyunsaturated fatty acids and formation of bioactive lipid mediators in human skin." Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/elucidating-the-metabolism-of-n3-polyunsaturated-fatty-acids-and-formation-of-bioactive-lipid-mediators-in-human-skin(773abedd-c726-4dab-890a-694a96b1c074).html.
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Human skin has distinct lipid metabolism and production of bioactive lipid mediators that can be modulated by nutritional supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFA), of which eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids exert anti-inflammatory effects. The aims of this project were to gain better understanding of their individual mechanisms in human epidermis and dermis. HaCaT keratinocytes, 46BR.1N fibroblasts, primary human epidermal keratinocytes and dermal fibroblasts were treated with EPA or DHA for 72h and then sham-irradiated or exposed to 15 mJ/cm2 ultraviolet radiation (UVR). Viability was measured by the MTT assay. The expression of cyclooxygenase-2 (COX-2), microsomal prostaglandin synthase-1 (mPGES-1) and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) proteins was explored by western blotting. Human skin explants (n=4 donors) were cultured for 3 or 6 days and supplemented with EPA, DHA or vehicle. Culture media were collected to evaluate tissue damage and PUFA cytotoxicity (lactate dehydrogenase assay). Epidermal and dermal lipid profiles were assessed by gas chromatography and liquid chromatography coupled to tandem mass spectrometry. Primary keratinocytes were treated with fatty acids and various lipid mediators for 48h. Their effect was determined by the scratch assay and transepithelial electrical resistance. UVR upregulated COX-2 in HaCaT and primary epidermal keratinocytes, but did not affect mPGES-1 and 15-PGDH protein expression. UVR upregulated COX-2 and mPGES-1 in 46BR.1N fibroblasts but had no effect on 15-PGDH expression. The same UVR dose did not alter the expression of COX-2, mPGES-1 and 15-PGDH in primary dermal fibroblasts. Only EPA attenuated COX-2 expression in HaCaT and primary keratinocytes and either EPA or DHA had any effect in 46BR.1N and primary fibroblasts. Skin explants showed initial post-biopsy tissue damage. EPA and DHA supplementation augmented cellular levels of the corresponding fatty acids in both epidermis and dermis to a different extent. Increased uptake of DHA in the dermis was accompanied by reduced arachidonic acid levels. EPA treatment stimulated the production of PGE3 and various HEPE in epidermis, while DHA treatment caused high levels of HDHA species in dermis. N-3 PUFA and their derivatives delayed wound healing, cell migration and epidermal barrier permeability, while n-6 PUFA lipids showed the opposite effect. Overall, these findings suggest that EPA and DHA differently affect skin cells and skin, with EPA preference in epidermis and DHA in the dermis. These results highlight the importance of differential skin responses that could be important in skin health and disease.
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Markovic, Vesna. "Induction of the Lipid Regulator PPAR-Delta in FoxO1 Overexpressed Skeletal Muscle." University of Toledo / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1525456674210299.
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Kang, Fan. "Carbon sources for starch and fatty acid synthesis in plastids from developing embryos of oilseed rape." Thesis, University of East Anglia, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.240398.
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Sudimack, Andrew George. "On the Effects of Membrane Fatty Acid Saturation on Cellular Metabolic Parameters." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1388763617.
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Miinalainen, I. (Ilkka). "Enoyl thioester reductases—enzymes of fatty acid synthesis and degradation in mitochondria." Doctoral thesis, University of Oulu, 2006. http://urn.fi/urn:isbn:9514282442.
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Abstract
Fatty acids are one of the most essential categories of biological lipids and their synthesis and degradation are vital for all organisms. Severely compromised phenotypes of yeast mutants and human patients, which have defective components in their degradative or synthetic processes for fatty acid metabolism, have highlighted the importance of these processes for overall metabolism. Most fatty acids are degraded by β-oxidation, which occurs in mitochondria and peroxisomes in mammals, whereas synthesis is catalyzed by cytosolic multifunctional peptides, although a synthesis system involving individual enzymes in mitochondria has been also proposed.
In this study a novel mitochondrial 2-enoyl thioester reductase Etr1p from the yeast Candida tropicalis, its homolog Mrf1p from Saccharomyces cerevisiae, and their mammalian ortholog were identified and characterized. Observations indicating that mitochondrial localization as well as enzymatic activity is needed to complement the respiratory-deficient phenotype of the mrf1Δ strain from S. cerevisiae suggests that Etr1p and Mrf1p might act as a part of the mitochondrial fatty acid synthesis machinery, the proper function of which is essential for respiration and the maintenance of mitochondrial morphology in yeast. The mammalian enzyme, denoted Nrbf-1p, showed similar localization, enzymatic activity, and ability to rescue the growth of the mrf1Δ strain suggesting that mammals are also likely to possess the ability and required machinery for mitochondrial fatty acid synthesis.
This study further included the characterization of another mitochondrial thioester reductase, 2,4-dienoyl-CoA reductase, which acts as an auxiliary enzyme in the β-oxidation of unsaturated fatty acids. The function of this gene was analyzed by creating a knock-out mouse model. While unstressed mice deficient in 2,4-dienoyl-CoA reductase were asymptomatic, metabolically challenged mice showed symptoms including hypoglycemia, hepatic steatosis, accumulation of acylcarnitines, and severe intolerance to acute cold exposure. Although the oxidation of saturated fatty acids proceeds normally, the phenotype was in many ways similar to mouse models of the disrupted classical β-oxidation pathway, except that an altered ketogenic response was not observed. This mouse model shows that a proper oxidative metabolism for unsaturated fatty acids is important for balanced fatty acid and energy metabolism.
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Chen, Z. (Zhijun). "Characterization of the 2-enoyl thioester reductase of mitochondrial fatty acid synthesis type II in mammals." Doctoral thesis, University of Oulu, 2008. http://urn.fi/urn:isbn:9789514289804.
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A data base search using the amino acid sequence of Saccharomyces cerevisiae Etr1p, the last enzyme of mitochondrial fatty acid synthesis type II (FAS II), revealed a highly similar human protein, NRBF-1. Expression of NRBF-1 in a yeast etr1Δ strain rescued its respiratory deficiency. NRBF-1 resides in mitochondria in cultured HeLa cells. The recombinant NRBF-1 is enzymatically active, reducing 2E-enoyl-CoAs to acyl-CoAs in an NADPH-dependent manner. Altogether, our data showed that NRBF-1 is a mitochondrial 2-enoyl-CoA reductase/2-enoyl thioester reductase (MECR/ETR1), the human functional counterpart of yeast Etr1p. In addition, MECR was also isolated from bovine heart. It turns out that mammals contain a mitochondrial FAS II pathway, in addition to cytoplasmic FAS I.
To investigate the functional mechanism of MECR/ETR1 at the molecular level, the protein was crystallized and the crystal structure determined. The apo-structure of MECR/ETR1 contains two sulfates in the nucleotide binding site and the domain arrangement resembles the NADPH-containing holo-structure of yeast Etr1p. The predicted mode of NADPH-binding and kinetic data suggest that Tyr94 and Trp311 play critical roles in catalysis. A pocket was found in the structure extending away from the catalytic site that can accommodate fatty acyl chains up to 16 carbons. An acyl carrier protein (ACP) binding site was also suggested.
To study the physiological function of mouse Mecr, two lines of transgenic mice overexpressing Mecr were generated. The Mecr transgenic mice developed cardiac and mitochondrial abnormalities. The phenotyping was carried out using echocardiography, heart perfusion, histology, and endurance testing. Our results suggest Mecr plays a role in mitochondrial and heart function. Therefore, inappropriate expression of the genes of FAS II may result in the development of cardiomyopathy.
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Stamey, Jennifer Anne. "Systemic and Intracellular Trafficking of Long-chain Fatty Acids in Lactating Dairy Cattle." Diss., Virginia Tech, 2012. http://hdl.handle.net/10919/38689.
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Marine oils are used as ration additives to provide omega-3 fatty acids to dairy
cows. Supplementing dairy cows with omega-3 fatty acid-rich feeds does not easily
increase quantities in milk fat of dairy cows because polyunsaturated fatty acids are
biohydrogenated in the rumen. Lipid encapsulation of omega-3 fatty acids provides
protection from biohydrogenation in the rumen and allows them to be available for
absorption and utilization in the small intestine. Lactating cows were supplemented with
rumen protected algae biomass or algal oil in a 4 Ã 4 Latin Square. Feeding lipid
encapsulated algae supplements increased docosahexaenoic acid content in milk fat while
not adversely impacting milk fat yield; however, docosahexaenoic acid was preferentially
esterified into plasma phospholipid, limiting its incorporation into milk fat. In the second
study, triglyceride emulsions of oils enriched in either oleic, linoleic, linolenic, or
docosahexaenoic acids were intravenously infused to avoid confounding effects of
triglyceride esterification patterns in the small intestine and to compare mammary uptake.
Milk transfer of fatty acids delivered as intravenous triglyceride emulsions was reduced
with increased chain length and unsaturation. Increased target fatty acids were evident in
plasma phospholipid, suggesting re-esterification in the liver. Transfer efficiencies were 37.8, 27.6, and 10.9±5.4% for linoleic, linolenic, and docosahexaenoic acid. Both liver
and mammary mechanisms may regulate transfer of long-chain polyunsaturates.
Intracellular fatty acid binding proteins (FABP) are cytoplasmic proteins that are
hypothesized to be essential for fatty acid transport and metabolism by accelerating longchain
fatty acid uptake and targeting to intracellular organelles, such as the endoplasmic
reticulum for triglyceride esterification. FABP3 mRNA is highly expressed in bovine
mammary and heart tissue, but is not present in MAC-T cells, a bovine mammary
epithelial cell line. When overexpressed in MAC-T cells, FABP3 does not appear to be
rate-limiting for fatty acid uptake in vitro and did not alter lipid metabolism. The function
of FABP3 in the mammary gland remains unclear.Ph. D.
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Ta, Nathan. "Role of glucose and glutamine in lipogenesis in the VM-M3 glioblastoma cell line and the inheritance of brain cardiolipin fatty acid abnormality in the VM/Dk mice." Thesis, Boston College, 2014. http://hdl.handle.net/2345/bc-ir:103739.
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Thesis advisor: Thomas SeyfriedLipids, in all their forms from structural components of the membranes (phosphoglycerides, glycolglycerolipids) to signaling molecules (IP3, DAG, prostaglandins, etc.,) post-translational modification of proteins (palmitoylated, farnesylated, prenylated, and GPI anchoring) play an essential role in cancer cell survival, proliferation, and metastasis. Alteration in structural lipids can impair transport, and signaling cascades. Abnormalities in lipids, such as cardiolipin (Ptd2Gro), impair mitochondrial function, bioenergetics, and could play a role in precipitatting the high incidence of spontaneous tumors in VM/Dk mice. This thesis explores the role of glucose and glutamine in their incorporation into lipids in the VM-M3 murine glioblastoma cell line as well as the inheritance of brain cardiolipin fatty acids abnormalities in VM/Dk mice. I used labeled [14C]-U-D-glucose and [14C]-U-L-glutamine to examine the profile of de novo lipid biosynthesis in the VM-M3 cell line. The major lipids synthesized included phosphatidylcholine (PtdCho), phosphatidylethanolamine (EtnGpl), phosphatidylinositol (PtdIns), phosphatidylserine (PtdSer), sphingomyelin (CerPCho), bis(monoacylglycero)phosphate (BMP) / phosphatidic acid (PtdOH), cholesterol (C), Ptd2Gro, and the gangliosides. The data show that the incorporation of labeled glucose and glutamine into synthesized lipids was dependent on the type of growth environment, and that the VM-M3 glioblastoma cells could acquire lipids, especially cholesterol, from the external environment for growth and proliferation. In addition, this thesis also explores and evaluates the abnormality of Ptd2Gro fatty acid composition in VM mice in comparison to B6 mice. Although previously reported, I confirmed the finding in the abnormal cardiolipin fatty acid composition in the VM mice. The abnormal brain cardiolipin fatty acid composition was found to be inherited as an autosomal dominant trait in reciprocal B6 x VM F1 hybrids for both male and female. Impaired cognitive awareness under hypoxia observed for the VM mice and reciprocal F1 hybrids is associated with abnormalities in neural lipid composition
Thesis (PhD) — Boston College, 2014
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Biology
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Bergmann, Hannes [Verfasser]. "Genetic predisposition for common-type obesity determines lipid metabolism responses to polyunsaturated fatty acid supplemented high-fat diets / Hannes Bergmann." Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2017. http://d-nb.info/115016798X/34.
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Le, Thi Thu Giang [Verfasser]. "Characterization of transcription factors important for fatty acid and lipid metabolism in the phytopathogen Fusarium graminearum / Thi Thu Giang Le." Hamburg : Staats- und Universitätsbibliothek Hamburg Carl von Ossietzky, 2011. http://d-nb.info/1237051223/34.
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Ding, Shih-Torng. "Lipid Metabolism and The Ontogeny of ACYLCoA:Cholesterol Acyltransferase and Fatty Acid-Binding Protein in Developing Embryos and Post-Hatch Turkeys /." The Ohio State University, 1996. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487933648649402.
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Sheppard, Micah J. (Micah James). "Modular pathway engineering of microbial fatty acid metabolism for the synthesis of branched acids, alcohols, and alkanes." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/91064.
Full textAbstract:
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2014.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 130-141).
Historically, microbial platforms have been used to synthesize a variety of chemical products and potential biofuels. More recently, increasingly complex metabolic pathways have been engineered by using novel hosts, modifying natural pathways, and establishing de novo pathways with enzymes taken from a variety of pathway contexts. Highly reduced and branched alkyl chains are potentially interesting targets for both flavor and fragrance compounds and as liquid fuel components. Here we report the engineering of microbial fatty acid synthesis to provide both CoA-dependent and fatty acid synthase platforms for previously undescribed routes to medium-chain length, branched acids. Specifically we produced six-carbon 4-methyl-valeric acid via a CoA-dependent route and nine-carbon 7-methyloctanoic acid via a fatty acid synthase. Specific variants of the platform pathways were used to demonstrate synthesis of potential liquid fuel targets. The CoA-dependent platform was used to create a redox-neutral pathway to 4-methyl-pentanol with a maximum theoretical energy efficiency of 100%. Both platforms were used to demonstrate the first reported synthesis of short- and medium-chain alkanes from three to seven carbons.
by Micah J. Sheppard.
Ph. D.
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Viswanadha, Srikant. "Alterations in Lipid Metabolism in Mouse Tissues and Hepatic Cell Lines in Response to the Trans10,Cis12-18:2 Isomer of Conjugated Linoleic Acid." Diss., Virginia Tech, 2003. http://hdl.handle.net/10919/28354.
Full textAbstract:
Conjugated linoleic acid (CLA) reduces adipose mass in several species. Studies were conducted to determine: 1) the effect of dietary trans10,cis12-CLA on growth, tissue fatty acid profile, mRNA expression for stearoyl-CoA desaturase (SCD) in adipose and liver, and mRNA expression for fatty acid synthase (FAS) in adipose of mice, 2) the effect of a dietary combination of trans-vaccenic acid (TVA) and trans10,cis12-CLA on delta9- desaturation, and 3) the effect of cis9,trans11-CLA, trans10,cis12-CLA, and carnitine palmitoyltransferase-1 (CPT-1) inhibitors on expression of mRNA for CPT-1 and fatty acid profile in mouse hepatocytes (AML-12) and human hepatoma cells (HepG2). In the first study, male or female mice were fed diets containing 0, 0.15%, or 0.30% trans10,cis12-CLA for 6 wk. Epididymal adipose weights (males) and inguinal adipose weights (females) decreased by 81% and 52%, respectively, in response to 0.30% trans10,cis12-CLA. Dry carcass weights decreased from 4.75 g for the control to 3.62 g for mice fed 0.30% trans10,cis12-CLA and the decrease was due to a reduction in ether extract. Liver weights increased linearly from 0.55 g (control) to 0.65 g (0.30% trans10,cis12-CLA). Dietary trans10,cis12-CLA (0.30%) reduced FAS and SCD mRNA in adipose by 60 and 30 % respectively, compared with the control, suggesting reduced lipogenesis and desaturation might be primary factors responsible for reducing body fat. In the second study, adult male or female mice were fed diets containing 0.40% TVA in combination with 0, 0.15, or 0.30% trans10,cis12-CLA for 10 d. Both TVA and trans10,cis12-CLA were incorporated into plasma, liver, adipose, muscle, and bone lipids proportional to their concentrations in the diets. Desaturation ratios were not affected in adipose, liver, and bone. However, ratios of 16:0 to 16:1 and 18:0 to 18:1 increased from 0.81 to 0.86 and 0.15 to 0.19 respectively, in response to dietary trans10,cis12-CLA (0.30%), suggesting inhibition of delta9 desaturation in muscle. In the third study, AML-12 or HepG2 cells were incubated with control media or media containing 15 uM etomoxir (ETM), 30 uM ETM, 15 uM hemipalmitoylcarnitinium (HPC), 30 uM HPC, 100 uM cis9,trans11-CLA, or 100 uM trans10,cis12-CLA for 24 h. Half the cells were harvested for analysis of fatty acids, mRNA for CPT-1, and cholesterol after 24 h. The remaining cells were incubated for an additional 24 h in control medium. Incorporation (% of total fatty acids) of trans10,cis12-CLA was greater than cis9,trans11-CLA in AML-12 (34 vs 23.6) and HepG2 (28 vs 18) cells. Cells incubated with trans10,cis12-CLA had higher ratios of 16:0 to 16:1, 18:0 to 18:1, and 18:2n6 to 20:4n-6, suggesting inhibition of delta9, delta5 , and delta6 desaturation. Cis9,trans11-CLA also reduced ratio of 18:2n-6 to 20:4n-6 in both cell lines. Trans10,cis12-CLA increased mRNA for CPT-1 in both cell lines compared with the control, suggesting enhanced oxidation of fatty acids. In addition, trans10,cis12-CLA caused a 4-fold and 5-fold increase in free cholesterol content of AML-12 and HepG2 cells, respectively. Overall, results demonstrated that trans10,cis12-CLA modulated lipid metabolism in tissues in vivo and altered fatty acid metabolism, cholesterol synthesis, and CPT-1 mRNA in hepatic cell lines in vitro.Ph. D.
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Denloye, Titilola Ifeoma. "Characterization of a glycerophosphodiester phosphodiesterase in the human malaria parasite Plasmodium falciparum." Diss., Virginia Tech, 2012. http://hdl.handle.net/10919/77090.
Full textAbstract:
Active lipid metabolism is a key process required for the intra-erythrocytic development of the malaria parasite, Plasmodium falciparum. Enzymes that hydrolyze host-derived lipids play key roles in parasite growth, virulence, differentiation, cell-signaling and hemozoin formation. Therefore, investigating enzymes involved in lipid degradation could uncover novel drug targets. We have identified in P. falciparum, a glycerophosphodiester phosphodiesterase (PfGDPD), involved in the downstream pathway of phosphatidylcholine degradation. PfGDPD hydrolyzes deacylated phospholipids, glycerophosphodiesters to glycerol-3-phosphate and choline. In this study, we have characterized PfGDPD using bioinformatics, biochemical and genetic approaches. Knockout experiments showed a requirement for PfGDPD for parasite survival. Sequence analysis revealed PfGDPD possesses the unique GDPD insertion domain sharing a cluster of conserved residues present in other GDPD homologues. We generated yellow fluorescent fusion proteins that revealed a complex distribution of PfGDPD within the parasite cytosol, parasitophorous vacuole and food vacuole. To gain insight into the role of PfGDPD, sub-cellular localization was modulated and resulted in a shift in protein distribution, which elicited no growth phenotype. Kinetic analyses suggest PfGDPD activity is Mg₂⁺ dependent and catalytically efficient at the neutral pH environment of the parasitophorous vacuole. Next, our aim was to determine the upstream pathway that provides deacylated glycerophosphodiesters as substrate for PfGDPD. We identified via bioinformatics, a P. falciparum lysophospholipase (PfLPL1) that directly generates the substrate. Knockout clones were generated and genotyped by Southern and PCR analysis. The effects of PfLPL1 knockouts on parasite fitness were studied, and the results showed that PfLPL1was not required for parasite survival and proliferation.Ph. D.
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Karalazos, Vasileios. "Sustainable alternatives to fish meal and fish oil in fish nutrition : effects on growth, tissue fatty acid composition and lipid metabolism." Thesis, University of Stirling, 2007. http://hdl.handle.net/1893/220.
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Traditionally, fish meal (FM) and fish oil (FO) have been used extensively in aquafeeds, mainly due to their excellent nutritional properties. However, various reasons dictate the use of sustainable alternatives and the reduction of the dependence on these commodities in fish feeds. Hence, the aim of the present thesis was to investigate the effects of the replacement of FM and FO with two vegetable oils (VO) and an oilseed meal on the growth performance, feed utilization, nutrient and fatty acids (FA) digestibility and tissue FA composition and metabolism in three commercially important European fish species. Specifically, in Experiment I crude palm oil (PO) was used to replace FO in diets for rainbow trout. In Experiments II and III FO was replaced with rapeseed oil (RO) in diets for Atlantic salmon at various dietary protein/lipid levels aiming also at further reductions of FM by using low protein (high lipid) diet formulations. In Experiments II and III the fish were reared at low and high water temperatures, respectively, in order to elucidate, also, the potential effects of temperature. Lastly, the effects of the replacement of FM with full fat soya meal (FFS) in Atlantic cod were investigated in Experiment IV. The results of the present thesis showed no negative effects on growth performance and feed utilization in rainbow trout when FO was replaced with PO. The dietary inclusion of RO improved the growth of Atlantic salmon, possibly, due to changes in the nutrient and FA digestibilities and FA catabolism while, the growth and feed utilization were unaffected by the dietary protein/lipid level. However, the growth of Atlantic cod was affected negatively by the replacement of FM with FFS. The proximate composition of the fish whole body was in most cases unaffected by dietary treatments. The changes in dietary formulations affected the dietary FA compositions and resulted in significant changes in the fish tissue FA compositions. It was clearly shown that the fish tissue total lipid FA composition reflects the FA composition of the diet, although specific FA were selectively utilized or retained in the tissues by the fish. These may have serious implications not only for fish metabolism and growth but also for the quality of the final product, especially in terms of possible reductions of n-3 HUFA.
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Houston, Sam James Silver. "Assessing EPA + DHA requirements of Sparus aurata and Dicentrarchus labrax : impacts on growth, composition and lipid metabolism." Thesis, University of Stirling, 2018. http://hdl.handle.net/1893/27444.
Full textAbstract:
The gilthead seabream (Sparus aurata) and European seabass (Dicentrarchus labrax) require n-3 long-chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for optimal growth and health. Due to the rapid growth of global aquaculture the quantity of marine oils used in aquafeeds has been limited, yet the overall quantity of oil in an aquafeed has increased by the addition of vegetable oil (VO) to supply dietary energy. For aquaculture to continue to grow more fish must be produced with less marine ingredients, yet EPA and DHA must be maintained at levels above fish requirements. This project set out to re-evaluate the requirement for EPA and DHA in gilthead seabream and European seabass. Two dose-response studies were designed and executed where juvenile seabream and seabass were fed one of six levels of EPA+DHA (0.2 – 3.2 % as fed). Biometric data were collected and analysed to determine new requirement estimates for EPA+DHA for fish of two weight ranges (24 – 80 g and 80 – 200 g). The effects of the dietary LC-PUFA gradient on lipid composition and metabolism were also considered.
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Almeida, Cotrim Bruno. "Synthesis of fatty acid derivatives of catechol compounds that exhibit negative modulation of food intake and antioxidant properties." Doctoral thesis, Universitat Pompeu Fabra, 2011. http://hdl.handle.net/10803/22690.
Full textAbstract:
Obesity constitutes a problem whose manifestations have
consequences in almost every field of the medicine and
nowadays there is a lack of pharmacological therapy
alternatives for its long term treatment. Lipidic compounds as
endocannabinoids and PPAR-α ligands are known to play an
important role in the modulation of appetite and metabolism.
Three series of fatty acid derivatives of catechol compounds
were synthesized and their biological activity evaluated.
Some of the synthesized compounds presented LDL
antioxidant activity and/or food intake modulation in an animal
model and their mechanism of action was also evaluated. The
pharmacodynamics of the synthesized compounds could be
explained by CB1 and PPAR-α interactions nevertheless it
does not explain the activity of all compounds.La obesidad es un problema cuyas manifestaciones tienen consecuencias en casi todos los campos de la medicina y actualmente existe una escasez de terapias farmacológicas para su tratamiento de uso continuo. Se sabe que algunos compuestos lipídicos como los endocanabinoides y ligandos del PPAR-α participan de manera importante en la modulación del apetito y en el metabolismo. Tres series de compuestos derivados de ácidos grasos con compuestos catecólicos fueron sintetizadas y sus actividades biológicas fueron evaluadas. Algunos de los compuestos presentó inhibición de la oxidación de la LDL y/o modulación de la ingesta en modelo animal y sus mecanismos de acción fueron también evaluados. La actividad de los compuestos pasa por interacciones con el receptor CB1 y el PPAR-α pero estas interacciones no explican la actividad de todos los compuestos
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Petkevicius, Kasparas. "The role of macrophage intracellular lipid partitioning in glucose and lipid homeostasis during obesity." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/285429.
Full textAbstract:
Obesity-associated metabolic disorders are amongst the most prevalent causes of death worldwide. Understanding how obesity leads to the development of the Metabolic Syndrome (MetS) and cardiovascular disease (CVD) will enable the development of novel therapies that dissociate obesity from its cardiometabolic complications. Our laboratory views the functional capacity of white adipose tissue (WAT), the organ designed for safe lipid storage, as a key factor in the development of MetS and CVD. At a genetically-defined stage of the aberrant WAT expansion that occurs during obesity, adipocytes undergo a functional failure, resulting in an impaired control of serum free fatty acid (FFA) concentration. In such setting, FFAs and their metabolic derivatives accumulate in other organs, where they cause lipotoxicity, leading to the development of insulin resistance and CVD. We therefore aim to understand the pathophysiological mechanisms that induce adipocyte dysfunction. The past two decades of research have established the immune system as an important regulator of WAT function. The number of adipose tissue macrophages (ATMs), the most abundant immune cell type in WAT, increases during obesity, resulting in WAT inflammation. Multiple genetic and pharmacological intervention studies of murine models of obesity have assigned a causal link between ATM pro-inflammatory activation and WAT dysfunction. However, while the propagation of inflammation in ATMs during obesity has been extensively studied, factors triggering ATM inflammatory activation are less clear. Recently, our lab has observed lipid accumulation in the ATMs isolated from obese mice. Lipid-laden ATMs were pro-inflammatory, leading us to hypothesise that aberrant lipid build-up in macrophages triggers WAT inflammation during obesity. This thesis expands on the initial findings from our lab and describes two novel mechanisms that potentially contribute to lipid-induced inflammatory activation of ATMs. In chapter 3, the role of de novo phosphatidylcholine (PC) synthesis pathway during lipotoxicity in macrophages is addressed. The first part of the chapter demonstrates that lipotoxic environment increased de novo PC synthesis rate in bone marrow-derived macrophages (BMDMs) and ATMs, and that loss of rate-limiting enzyme in de novo PC synthesis pathway, CTP:phosphocholine cytidylyltransferase a (CCTa) diminished saturated FFA-induced inflammation in BMDMs. In the second part, I show that macrophage-specific CCTa deletion did not impact on the development of WAT inflammation or systemic insulin resistance, but had a minor benefitial effect on hepatic gene transcription during obesity. Chapter 4 develops on recent observations of interactions between sympathetic nerves and macrophages in WAT. In the first part of the chapter, I demonstrate that stimulating B2-adrenergic receptor (B2AR), the main receptor for sympathetic neurotransmitter norepinephrine in macrophages, enhanced intracellular triglyceride storage by up-regulating diacylglycerol O-acyltransferase 1 (Dgat1) gene expression in BMDMs. The second part of the chapter shows that macrophage-specific B2AR deletion did not modulate systemic glucose and lipid metabolism during obesity, but mice lacking B2ARs in macrophages demonstrated augmented hepatic glucose production on a chow diet. Furthermore, systemic B2AR blockade or macrophage-specific B2AR deletion in mice did not affect the thermogenic response to cold exposure. Chapter 5 includes the characterisation of B2AR stimulation-induced changes to the global cellular proteome of BMDMs, and a subsequent validation of the role of candidate transcription factors in regulating B2AR agonism-induced gene expression in BMDMs.
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Kennedy, Sean Robert. "Bioactive fatty acids as dietary supplements for farmed fish : effects on growth performance, lipid metabolism, gene expression and immune parameters." Thesis, University of Stirling, 2007. http://hdl.handle.net/1893/389.
Full textAbstract:
Current feed formulations within the aquaculture industry have tended to rely on high dietary lipid thus offsetting relatively expensive protein as a source of energy. In this way, protein can be ‘spared’ for synthesis of new tissue and the high lipid content can also fulfil both fish and consumer essential fatty acid (EFA) requirements. However, the main disadvantage of feeding high lipid levels to farmed fish is a surplus of fat deposition in the flesh and other important tissues, which can detrimentally impact on quality characteristics central to the human consumer. However, based on previous work in other animal models, it is entirely feasible that supplementation of the diet with bioactive fatty acids such as conjugated linoleic acid (CLA) and tetradecylthioacetic acid (TTA) may mitigate the deleterious effects of feeding farmed fish high fat diets by reducing fat deposition in particular. The general objective of this research work was to test the hypothesis that CLA and/or TTA could augment growth, reduce fat deposition and enhance fatty acid composition via incorporation of these bioactive fatty acids, and increase n-3 highly unsaturated fatty acid (HUFA) levels in the flesh of commercially important fish species such as Atlantic salmon (Salmo salar), Atlantic cod (Gadus morhua L.) and rainbow trout (Oncorhynchus mykiss). This project also considered the influence of CLA and TTA on enzymes and transcription factors thought to be pivotal in lipid metabolism and fatty acid oxidation in particular. A subsidiary aim of this research work was to investigate the immunological impact of dietary CLA and TTA administration in these fish. The results of this project have revealed that the hypothesis was only partly proved. There was no effect in growth or biometry after either CLA or TTA supplementation in any of the fish species investigated. Additionally, there were few physiologically significant effects on fat levels on fish as a result of TTA or CLA administration. However, there were a number of effects on fatty acid metabolism including inhibition of steroyl coenzyme desaturase (SCD) in cod and trout in particular and also enhancement of hepatic n-3 HUFA levels in trout. Importantly, it was determined that both TTA and CLA could be incorporated into the flesh thus providing a vehicle through which these bioactive fatty acids can be delivered to the consumer. There were also a number of beneficial effects on activity and gene expression of a number of enzymes and transcription factors thought to be fundamental to the modulation of fatty acid oxidation in particular. However, the effects on gene transcription and biochemistry had little impact at the whole body level. This research work also showed that there were no detrimental effects on immune status after supplementation with dietary CLA or TTA. Conclusively, this thesis has contributed to the overall understanding of the influence of dietary CLA and TTA in farmed fish.
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Hansen, Christine. "Synthesis of Modified and Labelled Lipids for Analysis of Enzyme Mechanisms and Membrane Interactions." Doctoral thesis, Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2017. http://hdl.handle.net/11858/00-1735-0000-0023-3F6F-F.
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Sarafian, Magali. "A metabonomics study of the modulation of lipid and bile acid metabolism by the gut microbiota and consequences on obesity and fatty liver disease." Thesis, Imperial College London, 2016. http://hdl.handle.net/10044/1/53288.
Full textAbstract:
Obesity and fatty liver disease are characterised by an imbalance between energy intake and energy expenditure. Genetic and environmental factors strongly contribute to impaired energy homoeostasis and can trigger metabolic disorders such as hypertension, hyperglycaemia and hypercholesterolemia which are associated with type 2 diabetes, cardiovascular diseases and metabolic syndrome. The mechanisms underpinning obesity and its co-morbidity are poorly understood but dysregulation of lipid metabolism is likely to contribute and can be studied by metabolic profiling using UPLC-MS. Moreover, the host-gut axis has a strong influence on obesity and fatty liver disease development by modulation of metabolic pathways. The analytical quality of the metabolic profiling methods is critical to understand the aetiopathogenesis of obesity. Hence the aim of this PhD project is to investigate lipid metabolism in obesity and fatty liver disease. I developed and optimised a strategy for characterising the global lipid profile of plasma based on isopropanol precipitation and supplemented this with the development of a targeted assay for obtaining in depth profile of bile acids (BAs) (n=145) since BAs are known to play a specific role in obesity and fatty liver disease. Furthermore, BAs can provide insight into the role of the gut microbiota in obesity as they are metabolised by the gut microbiota. The analytical pipeline for lipid and BA analysis are subsequently applied for two human clinical studies. i) The metabolic signatures associated with subcutaneous and visceral obesity were investigated. A significant increase of LPC (16:0), unconjugated BAs and sulphated BAs with a decrease of PC (16:0/20:3), taurine conjugates was observed in visceral obesity compared to subcutaneous obesity. ii) Subtle disease progression in fatty liver disease, NAFLD and NASH was evaluated. A significant increase of triacylglycerols, hyocholic acid and tauro-conjugated BAs with a decrease of phosphocholines were observed in NASH compared to NAFLD. This phD project illustrated that metabonomic instrumentations (UPLC-MS and UPLC-MS/MS) are non-invasive and powerful analytical techniques to diagnose obesity and fatty liver disease. In addition, metabonomic analysis of urine and blood samples may offer the possibility to optimise individual diagnosis and management of patients with obesity and fatty liver disease.
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Keon, Brigitte H. "Fatty acid synthase is a major polypeptide constituent of cytosolic lipoprotein and is associated with components of the milk lipid secretory pathway." Diss., This resource online, 1993. http://scholar.lib.vt.edu/theses/available/etd-05042006-164523/.
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Al-Othman, Abdullah Abdulrahman. "Influence of copper deficiency on liver morphology, aortic integrity, plasma lipoprotein and hepatic lipid profiles, and hepatic fatty acid synthesis in vivo." Diss., The University of Arizona, 1992. http://hdl.handle.net/10150/185745.
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Three studies were designed to investigate the influence of dietary copper (Cu) on liver morphology, aortic integrity, lipid composition of lipoproteins, fatty acid profile of hepatic lipids, as well as in vivo hepatic fatty acid synthesis. Animals were randomly assigned to two dietary Cu treatments (deficient and adequate). Reductions in body weight, liver Cu content, and hematocrit, as well as elevations in liver weight and plasma volume were observed in animals fed Cu-deficient diet. Electron micrographs suggest that the Cu-deficient liver parenchymal cells contain a higher number of mitochondria, a more extensive network of rough endoplasmic reticulum and an increased quantity of chromatin in nucleus. Female hamsters fed the low Cu diet demonstrated a disruption and folding of collagen fibrils in the aorta. The percentage of total plasma cholesterol carried by LDL was increased from 20 to 24% but was reduced from 71 to 68% for HDL as a result of Cu deficiency. In LDL the percent composition of triglycerides and phospholipids were increased by 25% but that of cholesterol was reduced by 13%. With exception of smaller increases in VLDL protein (52%) and phospholipid (60%) pool size, as well as the more than 3-fold increases in LDL triglyceride and phospholipid plasma pool size, the plasma pool size for the rest of the lipoprotein components were increased about 2-fold in Cu-deficient hamsters. Furthermore, Cu deficiency altered the fatty acid composition of hepatic triglycerides, cholesteryl esters and phospholipids. The percent composition of palmitoleic (16:1 n-7) was reduced and arachidonic acid was elevated for all lipids in hamsters fed Cu-deficient diet. The percentage of stearic acid (18:0) was increased, and that of oleic (18:1 n-9) acid was decreased in the hepatic phospholipids and triglycerides of Cu-deficient animals. In study III, incorporation of [1-¹⁴C]acetate into fatty acids was used to determine the capacity of hepatic tissue to synthesize fatty acids. As a result of Cu deficiency, a 2.1-fold increase in hepatic total fatty acid synthesis was demonstrated.
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Roberts, Matthew D. "Lipidomic investigations into the phospholipid content and metabolism of various kinetoplastids." Thesis, University of St Andrews, 2017. http://hdl.handle.net/10023/16983.
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This work expands the knowledge on phospholipid metabolism in the kinetoplastid parasites: T. brucei, T. cruzi, Leishmania spp. that cause neglected tropical diseases and the related non-human pathogenic Crithidia fasiculata. As a close relative of parasitic kinetoplasts, specifically Leishmania, it is hypothesised that Crithidia fasiculata possesses a similar lipid biosynthetic capability and therefore represent an attractive model organism. Database mining the Crithidia genome revealed the ability to biosynthesise all of the main phospholipid species. Utilising various lipidomic techniques, a high level of an ω-6 18:3 fatty acid was observed, alongside an uncommon Δ19:0 fatty acid that was later identified to be exclusive attributed to PE species. Sphingolipid metabolism was shown to resemble that of Leishmania and T. cruzi, given the exclusive production of inositol-phosphoceramide species and no sphingomyelin species being observed. Using labelled precursors, Crithidia were seen to uptake and incorporate extracellular inositol into both phosphatidylinositol and inositol-phosphoceramide species. Crithidia were also shown to utilise both the Kennedy pathway and methylation of phosphatidylethanolamine to form phosphatidylcholine. The phospholipidome of T. cruzi revealed several phosphatidylserine species for the first time, suggesting a functional phosphatidylserine synthase. Current knowledge of T.cruzi sphingolipid biosynthesis was also confirmed as only inositol xxxi phosphoceramide species were observed. The identification and subsequent characterisation of novel phosphonolipid species are reported for the first time. Utilising lipidomic methodologies and labelled precursors, the relative contribution of the intracellular inositol pools within bloodstream and procyclic T. brucei towards PI biosynthesis was examined. This highlighted that the synthesis/turnover rates for specific phosphatidylinositol and inositol-phosphoceramide species are unequal. Efforts to optimise media conditions highlighted that under reduced levels of serum/glucose/inositol, bloodstream T. brucei unexpectedly adjusts its inositol metabolism. The procyclic parasite exemplifies this fact, as under inositol/glucose deficient media conditions they appear to have adapted to utilising glucogenesis and inositol de-novo synthesis. This work highlights that these parasites are rapidly dividing, their unique features of lipid metabolism may be exploitable for drug discovery purposes.
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Reveneau, Carine. "Dietary source and availibility [i.e. availability] of fatty acids to manipulate ruminal protozoa, metabolism of fat, and milk fatty acid profile in lactating dairy cows." The Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1204659455.
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Herdmann, Andrea [Verfasser], Gerhard [Akademischer Betreuer] Jahreis, Steffen [Akademischer Betreuer] Maak, and Nigel [Akademischer Betreuer] Scollan. "Exogenous effects of alpha-linolenic and linoleic acid on the fatty acid distribution and the regulation of lipid metabolism in ruminant tissues / Andrea Herdmann. Gutachter: Gerhard Jahreis ; Steffen Maak ; Nigel Scollan." Jena : Thüringer Universitäts- und Landesbibliothek Jena, 2012. http://d-nb.info/1025255917/34.
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Gutbrod, Philipp [Verfasser]. "Studies on fatty acid de novo synthesis and metabolism in free-living and parasitic nematodes and their feeding sites in plants / Philipp Gutbrod." Bonn : Universitäts- und Landesbibliothek Bonn, 2016. http://d-nb.info/1137010282/34.
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Nguyen, Phuong Jean. "Intervention de la carnitine au cours du développement normal ou affecté chez Arabidopsis thaliana, en lien avec le métabolisme des lipides." Thesis, Compiègne, 2014. http://www.theses.fr/2014COMP1839/document.
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La modification des profils spécifiques en acides gras (AG) dans des huiles végétales peut servir à l’amélioration de leur qualité nutritionnelle, mais également à l’émergence d’une industrie biosourcée où les AG peuvent représenter une alternative aux ressources carbonées fossiles. Cependant des difficultés à modifier le profil en AG des huiles végétales, partagées par l’ensemble des équipes de recherche impliquées subsistent. Bien que la biosynthèse des AG est aujourd’hui bien caractérisée chez les plantes, des incertitudes persistent concernant les voies de transfert des AG du pool d’acyl-CoA vers les précurseurs lipidiques, et les formes de transport entre les différents compartiments impliqués dans les synthèses lipidiques. La carnitine est un acteur essentiel du trafic intracellulaire des AG chez l’animal et la levure. La présence avérée chez la plante d’acyl-Carnitines au côté de la carnitine libre, et la mise en évidence d’activités enzymatiques associées, prouvent également le lien entre la carnitine et le métabolisme des AG. Le travail de cette thèse a donc porté sur un approfondissement des connaissances sur le rôle de la carnitine dans le métabolisme lipidique chez Arabidopsis thaliana. A ce titre, nous avons pu montrer par LC-QQQ-MS/MS dans nos extraits végétaux, que l’oléoyl-, la palmitoyl- et la stéaroyl-Carnitine sont les espèces majoritaires et correspondent aux 3 AG (C18:1, C16:0 et C18:0) principalement synthétisés et exportés des plastes, pour alimenter la synthèse lipidique de la voie eucaryotique. De plus, une augmentation significative des teneurs en acyl-Carnitines a été mesurée dans des processus développementaux nécessitant une forte synthèse de glycérolipides, tels que le développement post-Germinatif (2 j post-Imbibition) ou lors de l’organogenèse racinaire, en concomitance avec le niveau d’expression des gènes marqueurs de la synthèse lipidique eucaryotique. D’autre part, la comparaison des teneurs en acyl-Carnitines et en carnitine estérifiée a révélée un résultat inédit montrant qu’une grande fraction de la carnitine est estérifiée à des AG inhabituels ou des acides organiques que nous cherchons actuellement à identifier par LC-QTOF-MS/MS. Ainsi, l’ensemble de nos résultats suggèrent que la carnitine pourrait être impliquée dans le trafic intracellulaire d’AG pour la synthèse de lipides eucaryotiques et de lipides particuliers et/ou dans la prise en charge d’acides organiques encore non identifiés dans les plantesSpecific modification of fatty acid profiles (FA) in vegetable oils can help to improve their nutritional quality but also to the development of a bio-Based industry where FA may represent an alternative to fossil fuel sources. However problems to modify the FA profile of vegetable oils still remain and are shared by all the teams involved. Although the biosynthesis of AG is now well characterized in plants, uncertainties remain about the tranfert of AG of acyl-CoA pool to lipid precursors and the forms of transport between different compartments involved in lipid synthesis. Carnitine plays an essential role in intracellular trafficking of FA in animals and yeast. The known presence of acyl-Carnitines in plant alongside the free carnitine, and measurement of associatied-Enzymatic activities also show the link between FA metabolism and carnitine. During this thesis we tried to improve our understanding of the role of carnitine in lipid metabolism in Arabidopsis thaliana. We have shown by LC-QQQ-MS / MS in our plant extracts that oleoyl-, palmitoyl- and stearoyl-Carnitine are the predominant species and correspond to the three main AG (C18:1, C16:0 and C18:0) synthesized and exported from the plastids to supply the lipid synthesis of the eukaryotic pathway. Moreover, a significant increase of the levels of acyl-Carnitines were measured in developmental processes requiring high glycerolipid synthesis, such as the post-Germinative growth (2 days post-Imbibition) during root organogenesis, concomitantly with the level of expression of the eukaryotic lipid synthesis marker genes. Furthermore, comparison of the levels of acyl-Carnitine and carnitine ester revealed an unpublished results showing that a large fraction of carnitine is esterified to unusual FA or organic acids that we are currently identifing by LC QTOF-MS/MS. Thus, all of our results suggest that carnitine could be involved in the intracellular traffic of FA for the synthesis of lipids and particular eukaryotic lipids and/or in the transport of yet unidentified organic acids in plants
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Gellibert, Françoise. "Synthese d'analogues structuraux a motif captodatif et de nouveaux metabolites de l'acide arachidonique : actions sur la 5-lipoxygenase." Université Louis Pasteur (Strasbourg) (1971-2008), 1988. http://www.theses.fr/1988STR13031.
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La synthese d'inhibiteurs de la biosynthese des leucotrienes a ete developpee selon deux voies: -synthese de metabolites naturels de l'acide arachidonique (monoepoxides) -synthese de produits analogues de l'acide arachidoniques susceptibles de stabiliser l'intermediaire radicalaire forme au cours de la premiere etape de la 5-lipoxygenase
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Buzelle, Samyra Lopes. "Metabolismo de ácidos graxos e glicerol no tecido adiposo branco de camundongos com resistência à insulina induzida pela dieta hiperlipídica." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17131/tde-21072016-163652/.
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Camundongos Swiss, quando submetidos à dieta hiperlipídica (HL), apresentam considerável ganho ponderal e de depósitos adiposos, tornando-se obesos e resistentes à insulina. O objetivo deste trabalho foi avaliar o efeito da dieta HL por 8 semanas no perfil inflamatório, síntese de triacilglicerol (TAG) com ênfase na vias de geração de glicerol-3-fosfato (G3P) e lipólise nos tecidos adiposos brancos (TAB) retroperitoneal (RETRO) e epididimal (EPI) de camundongos. Camundongos Swiss foram alimentados com as dietas: controle (CT) - dieta purificada (AIN-93G); ou HL - dieta AIN-93G modificada contendo 35% de lipídeos (4% de óleo de soja e 31% de gordura suína). Os camundongos alimentados com a dieta HL apresentaram uma maior massa corporal, acompanhada pelo aumento nos tecidos RETRO e EPI, além de desenvolverem resistência à insulina constatada no teste de tolerância à glicose (TTG), hiperglicemia e hiperinsulinemia. O conteúdo protéico da pAKT, avaliado por western blot (WB), e a adiponectina, dosada em homogenados dos tecidos adiposos, estão reduzidos apenas no EPI. Houve aumento na expressão gênica de MCP-1 e PAI-1, e foi observada menor área dos adipócitos no EPI, sem alteração no RETRO dos animais HL. A síntese de novo de ácidos graxos (AG), avaliada pela incorporação de 3H de 3H2O em AG foi maior em ambos os TAB, porém a captação de AG das lipoproteínas circulantes avaliada pela atividade e expressão da lipase lipoproteica (LPL) aumentou no EPI e reduziu no RETRO. A dieta HL induziu aumento na fosforilação do glicerol, avaliada pela atividade e conteúdo da GK que aumentaram nos dois TAB, e maior incorporação de 1-14C-glicerol em TAG no EPI. A captação de glicose in vitro e conteúdo do GLUT- 4, que indicam atividade da via glicolítica foram reduzidos no EPI e RETRO, assim como a gliceroneogênese avaliada pela incorporação de 1-14C-piruvato em TAG, sem alterações na atividade e conteúdo da fosfoenolpiruvato carboxiquinase (PEPCK). A atividade lipolítica basal foi avaliada in vitro pela liberação de glicerol por adipócitos isolados, e não foi alterada pela ingestão de dieta HL, porém quando estimulada por noradrenalina a liberação de glicerol foi menor nos animais HL, assim como as fosforilações da ATGL e HSL e conteúdo do receptor adrenérgico ?3. A dieta HL levou a uma redução no conteúdo de PPAR? e aumento de ATF3 em ambos os tecidos. No EPI houve aumento de pCREB, pSTAT3 e RGS2 em relação aos controles enquanto no RETRO a única diferença encontrada foi a menor pSTAT3. Nossos resultados demonstram que o aumento nos TAB é resultado de maior síntese e captação de AG, e que o G3P necessário para a esterificação a TAG é proveniente principalmente da fosforilação direta do glicerol pela GK; além disso, a reduzida lipólise também parece contribuir para esse quadro. Nos animais HL, o EPI parece ser mais propenso aos efeitos da dieta do que o RETROSwiss mice when subjected to high fat diet (HFD), shown considerable weight gain and adipose depots, becoming obese and insulin resistant. The aim of this study was to evaluate the effect of HFD diet for 8 weeks in the inflammatory profile, triacylglycerol (TAG) synthesis with emphasis in glycerol-3-phosphate (G3P) generation pathways and lipolysis in retroperitoneal (RETRO) and epididymal (EPI) white adipose tissue (WAT) of mice. Swiss mice were fed with diets: control (CT) - purified diet (AIN-93G); or HFD - purified diet (AIN-93G) plus 35% of fat (4% soybean oil and 31% of lard). Mice fed a HFD diet had a higher body mass, accompanied by an increase in RETRO and EPI tissues, in addition to developing insulin resistance, evidenced by glucose tolerance test (GTT), hyperglycemia and hyperinsulinemia. The protein content of pAKT, accessed by western blot, and adiponectin, measured in WAT homogenates, are reduced only in EPI. There was an increase in gene expression of MCP-1 and PAI-1, and was observed smaller area of adipocytes in EPI, with no change in RETRO of HFD fed animals. De novo synthesis of fatty acids (FA), evaluated by incorporation of 3H from 3H2O in FA was higher in both TAB, but the uptake of FA, from blood lipoproteins, evaluated by the activity and expression of lipoprotein lipase (LPL) was increased in EPI and reduced in RETRO. HFD induced increase in phosphorylation of glycerol, evaluated by the activity and content of glycerolkinase (GyK) which increased in both TAB and greater incorporation of 1-14C-glycerol in the TAG only in EPI. The in vitro glucose uptake and GLUT-4 content, which indicates the activity of the glycolytic pathway were reduced in EPI and RETRO, as well as glyceroneogenesis assessed by the incorporation of 1-14C- pyruvate into TAG without changes in the activity and contents of phosphoenolpyruvate carboxykinase (PEPCK). The basal lipolytic activity was evaluated in vitro by glycerol releasing from isolated adipocytes, and was not altered by HFD intake, but when stimulated by noradrenaline glycerol release was lower in HFD animals as well as the phosphorylation of ATGL and HSL and ?3 adrenergic receptor content. HFD led to a reduction in the content of PPAR gamma and an increase in ATF3 in both tissues. In EPI there was an increase in pCREB, pSTAT3 and RGS2 while in RETRO the only difference was reduced pSTAT3. Our results shown that TAB increase is result of increased FA synthesis and uptake, and G3P required for esterification TAG comes mainly from direct phosphorylation of glycerol by GyK; Furthermore, reduced lipolysis also seems to contribute to this scenario. HFD effects seem to be more prominent in EPI than in RETRO
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Gimple, Ryan Christopher. "Epigenetic Landscapes Identify Functional Therapeutic Vulnerabilities in Glioblastoma." Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1587732572817921.
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Okada, Livia Samara dos Reis Rodrigues. "Avaliação proteômica e lipidômica de pacientes com esteato-hepatite não alcoólica tratados com ácidos graxos ômega-3." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5168/tde-13112017-121159/.
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INTRODUÇÃO: A esteato-hepatite não alcóolica (NASH) é considerada problema de saúde pública, dada sua crescente incidência e seu possível papel na carcinogênese hepato-celular. Terapias atuais envolvem alterações de dieta e estilo de vida, mas têm seu resultado prejudicado pela baixa aderência dos pacientes. Abordagens farmacológicas ainda são precárias. Uma grande dificuldade no manejo de NASH reside no limitado entendimento de sua fisiopatologia, que parece envolver complexas alterações metabólicas e inflamatórias. Ácidos graxos poli-insaturados ômega-3 (AGPIs n-3) são reconhecidos por suas propriedades moduladoras do metabolismo lipídico e da inflamação, e estão diminuídos em pacientes com NASH. O uso clínico de AGPIs n-3 tem mostrado benefício no controle da esteatose e na produção de marcadores da resposta metabólica e inflamatória em NASH, embora com algumas observações contraditórias. A compreensão de mecanismos moleculares modulados por AGPIs n-3 em NASH podem ser úteis para identificar alvos moleculares que auxiliem no desenho de intervenção farmacológica efetiva. Nesse sentido, ciências ômicas são particularmente úteis para a compreensão de mecanismos moleculares com alto valor translacional para a prática clínica e podem contribuir para a identificação desses alvos. OBJETIVO: O presente estudo avaliou a resposta proteômica hepática e lipidômica plasmática de pacientes com NASH perante o tratamento com AGPIs n-3. MÉTODO: As avaliações proteômicas e lipidômicas foram desenvolvidas por espectometria de massas e/ou cromatografia gasosa em amostras de biópsias hepáticas e plasma coletadas de pacientes envolvidos em estudo preliminar, realizado no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. O referido estudo envolveu pacientes adultos, de ambos os sexos e com diagnóstico de NASH tratados diariamente, durante 6 meses, com 3 cápsulas contendo mistura de óleo de linhaça e óleo de peixe [0,315 g AGPIs: sendo 0,065 g de ácido eicosapentaenoico (EPA), 0,050 g de docosahexaenoico (DHA) e 0,2 g alfa linolênico (ALA) por cápsula]. Pacientes, após o tratamento com AGPIs n-3, que apresentaram altas concentrações plasmáticas de ALA e/ou DHA e/ou baixas de ácido araquidônico (AA) mostraram melhora parcial das alterações de histologia hepática. No presente estudo, avaliamos as vias proteômicas e marcadores lipidômicos resultantes do tratamento com AGPIs n-3. Isto foi feito por meio da comparação, antes (grupo AT) e depois do tratamento (grupo DT), de pools de tecido hepático (análise por interactoma) e amostras de plasma (OPLS-DA). RESULTADOS: Foram identificadas proteínas hepáticas, exclusivamente e/ou alteradamente expressas, no grupo DT, relacionadas com vias de matriz celular, metabolismo lipídico, de estresse oxidativo, e de retículo endoplasmático e respiração celular. Com excessão da via de matriz celular, a análise do interactoma revelou alteração funcional significativa das vias moduladas por essas proteínas. Em conjunto, essas alterações foram sugestivas de diminuição de lipotoxicidade, estresse oxidativo e respiração anaeróbia, e aumento de respiração aeróbia após tratamento com AGPIs n-3. Estas modificações são marcadores potenciais de melhora de função de retículo endoplasmático e mitocondrial. Em adição, após o tratamento com AGPIs n-3, o perfil lipidômico plasmático mostrou-se alterado com significativo aumento de glicerofosfolípides, ALA e EPA, e diminuição de ácido araquidônico (n-6) e da razão AGPIs n-6/n-3. Estes dados são concordantes com potencial melhora das funções de retículo endoplasmático e mitocondriais. CONCLUSÃO: O tratamento com AGPIs n-3 em pacientes com NASH influenciou favoravelmente o perfil proteômico hepático e lipidômico sistêmico. Em conjunto, essas alterações sugerem melhora da função de retículo endoplasmático e mitocondrial, com potencial impacto na homeostase celular, por meio da modulação de diferentes vias biológicasINTRODUCTION: Non-alcoholic steatohepatitis (NASH) is considered a public health problem, given its increasing incidence and its possible role in hepatocellular carcinogenesis. Current therapies involve diet and lifestyle changes, but its applicability suffers from low patients adherence. Pharmacological approaches are still missing. A main difficulty in the NASH management lies in the limited understanding of its pathophysiology, which seems to involve complex metabolic and inflammatory disturbances. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are recognized for its modulatory properties on lipid metabolism and inflammation and are decreased in patients with NASH. The clinical use of these PUFAs has shown benefit in controlling steatosis and the production of metabolic and inflammatory response markers in NASH, despite some conflicting reports. Understanding mechanisms modulated by n-3 PUFAs in NASH may be useful for identifying molecular targets that could assist in the design of effective pharmacologic interventions. In this sense, omics sciences are particularly useful for understanding molecular mechanisms with high translational value to clinical practice and may contribute to the identification of these targets. AIM: This study evaluated the liver proteomic and plasma lipidomics responses of patients with NASH towards treatment with n-3 PUFAs. METHODS: The proteomic and lipidomic evaluations were studied by mass spectrometry and / or gas chromatography in samples from liver biopsies and plasma collected from patients enrolled in a preliminary clinical trial of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. This study involved adult patients of both sexes diagnosed with NASH treated daily for 6 months, with 3 capsules containing a mixture of linseed and fish oils [0.315 g PUFAs: 0.065 g eicosapentaenoic acid (EPA) , 0.050 g docosahexaenoic (DHA) and 0.2 g alpha linolenic acid (ALA) per capsule]. Patients, after treatment with n-3 PUFAs, with higher concentrations of ALA and DHA and lower arachidonic acid (AA) showed improvement of liver histology alterations. In the present study we evaluated the proteomics pathways and lipidomics markers resulted from treatment with PUFAs n-3. This was performed by comparing, before (BT group) and after (AT group) treatment, liver tissue pools (analysis interactome) and plasma samples (OPLS-DA). RESULTS: It was identified, in a way exclusive and altered, the expressed liver proteins in AT group, related to pathways of cellular matrix, lipid metabolism, oxidative and endoplasmic reticulum stress and cellular respiration. With the exception of cell matrix, the analysis of the interactome revealed substantial functional alterations of the pathways modulated by these proteins. Together, these changes were suggestive of decreased lipotoxicity, oxidative stress and anaerobic respiration and increased aerobic respiration following treatment with PUFAs n-3. These modifications are potential markers of endoplasmic reticulum and mitochondrial functions improvement. In addition, after treatment with n-3 PUFAs, the lipidomics profile was modified, with significant increase in glycerophospholipids, ALA and EPA and decrease of arachidonic acid (AA) and n-6/n-3 AGPIs ratio. These findings are concordant with potential improvement of reticulum endoplasmic and mitochondrial functions. CONCLUSION: In patients with NASH the treatment with n-3 PUFAs favorably influenced hepatic proteomic and systemic lipidomics profiles. Together, these changes suggest improved endoplasmic reticulum and mitochondrial functions, with potential impact on cellular homeostasis through the modulation of different biological pathways
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Najjar, Amal. "Etude quantitative de la sécrétion de lipase, de la lipolyse et du stockage de lipides chez Yarrowia lipolytica lors de sa croissance en présence d'huile d'olive." Thesis, Aix-Marseille 2, 2010. http://www.theses.fr/2010AIX22100/document.
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La sécrétion de lipase, la lipolyse extracellulaire et l’absorption des acides gras (AGL) ont été étudiés chez Yarrowia lipolytica (YL) en présence d’huile d’olive et/ou de sucrose. Des mesures d’activité lipase et d’immuno-révélation ont montré que l’activité lipase présente dans le milieu de culture provenait principalement de la lipase YLLIP2. L’huile d’olive induit la production de lipase qui est principalement associée aux cellules pendant les premières heures de cultures. YLLIP2 est ensuite libérée dans le milieu de culture avant d’être totalement dégradée par les protéases. Les triglycérides (TG) sont dégradés alors que la lipase est encore attachée aux cellules. Les produits de lipolyse présents dans le milieu de culture et à l’intérieur des cellules ont été quantifiés par chromatographie TLC-FID et GC. Les niveaux intracellulaires d’AGL et de TG augmentent transitoirement et dépendent de la source de carbone utilisée. Une accumulation maximum de 37,8 % w/w de lipides est observée avec l’huile d’olive seule. Cette étude montre que la levure YL est un modèle intéressant pour étudier la lipolyse extracellulaire et l’absorption des acides gras par les cellulesLipase secretion, extracellular lipolysis and fatty acid (FFA) uptake were quantified in Yarrowia lipolytica (YL) grown in the presence of olive oil and/or sucrose. Lipase assays and western blot analysis indicated that the lipase activity measured in YL cultures mainly resulted from YLLIP2 lipase. Lipase production was triggered by olive oil and YLLIP2 remained associated with the yeast cells during the first hours of culture. It was then released in the culture medium before it was totally degraded by the alkaline protease. Olive oil triglycerides (TG) were degraded when the lipase was still attached to the cell wall. The fate of lipolysis products in the culture medium and inside the yeast cell were investigated by quantitative TLC-FID and GC analysis. Intracellular levels of FFA and TG increased transiently and were dependent on the carbon sources. A maximum fat storage of 37.8% w/w was observed with olive oil alone. The present study shows that yeasts are interesting models for studying extracellular lipolysis and fat uptake by the cell
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Madeira, Marta Sofia Morgado dos Santos. "Feeding strategies to improve fat partitioning and meat quality in pigs." Doctoral thesis, Universidade de Lisboa. Faculdade de Medicina Veterinária, 2013. http://hdl.handle.net/10400.5/6292.
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Tese de Doutoramento em Ciências Veterinárias. Especialidade de Produção Animal.Modern commercial pig breeds usually produce very lean meat with poor eating quality. Thus, strategies to increase intramuscular fat (IMF) content and consequently to improve sensorial meat quality are needed. In view of this, our investigation explores the potential of feeding strategies based on reduction of dietary protein to improve intramuscular fat and carcass fat partitioning in pigs and to study the associated genetic mechanisms. In a first experiment, three diets differing in dietary protein and lysine levels (control diet with 17.5% crude protein, reduced protein diet – RPD with 13% of crude protein, and reduced protein diet adjusted with lysine – RPDL) were applied to two genetic divergent pig genotypes (30 Alentejano purebred, fatty and 30 commercial crossbred pigs, lean). In a second experiment, six diets differing in dietary protein (16 vs. 13% of crude protein) and arginine and/or leucine supplementation were applied on 54 commercial crossbred pigs. The effects of these diets on growth performance, carcass traits, IMF content, meat quality, subcutaneous adipose tissue (SAT) deposition, fatty acid composition and mRNA levels of genes controlling lipid metabolism were evaluated. The results from the first experiment showed that RPD increase IMF but decrease the productive performance in commercial crossbred pigs but not on Alentejano pigs, suggesting that lysine restriction mediates the effect of RPD on muscular lipid deposition. The effect of RPD on IMF of crossbred pigs was accompanied by an increased stearoyl-CoA desaturase (SCD) and PPARγ mRNA levels. The backfat thickness did not change with RPD, but total fatty acid content increased in both genotypes. In addition, this result reflects a tendency for higher sensory scores in crossbred pigs. The Alentejano pigs showed higher sensory scores than crossbred pigs, although RPD increased the juiciness of crossbred pigs. In the second experiment, reduced protein diet increased both IMF and backfat thickness. However, the observed increase in IMF was also accompanied by increased SCD expression but did not improved meat sensory traits. Neither arginine nor leucine dietary supplementation increased IMF content. Nevertheless, arginine introduced an off-flavour of meat. The only relevant effect of arginine was increasing the fat content of adipose tissue (and consistent up-regulation of fatty acid synthase (FASN) and SCD genes) and a slightly decrease in 20:5n-3 and of total n-3 PUFA in muscle. Leucine supplementation resulted on up-regulation of muscle SCD and FASN reflected in higher 18:1c9 and 16:0 proportions and lower PUFA proportions. The results suggested that fat partitioning can be modulated and pork quality improved with reduced protein diets without lysine adjustment.
RESUMO - Estratégias alimentares para melhorar a partição da gordura corporal e a qualidade da carne em suínos - As raças modernas de suínos comerciais normalmente produzem carne muito magra com baixa qualidade sensorial. Deste modo, são necessárias estratégias para aumentar o teor gordura intramuscular (GIM) e consequentemente melhorar a qualidade sensorial da carne. Neste sentido, a nossa investigação explora o potencial de estratégias alimentares baseadas na redução de proteína na dieta para melhorar a GIM e a partição da gordura na carcaça em suínos e também estudar os mecanismos genéticos associados. No primeiro ensaio experimental, três dietas com níveis de proteína e lisina diferentes (dieta controlo, com 17.5% de proteína bruta, dieta reduzida em proteína – RPD com 13% de proteína bruta e uma dieta reduzida em proteína ajustada com lisina – RPDL) foram aplicadas a suínos de dois genótipos diferentes (30 Alentejanos puros e 30 comerciais cruzados). Num segundo ensaio, seis dietas com níveis de proteína diferentes (16 vs. 13%) e suplementação de arginina e/ou leucina foram aplicadas a 54 suínos comerciais cruzados. Foram avaliados os efeitos destas dietas na performance de crescimento, nas características da carcaça, no teor de GIM, na qualidade da carne, na deposição do tecido adiposo subcutâneo, na composição em ácidos gordos e nos níveis de mRNA dos genes que controlam o metabolismo lipídico. Os resultados do primeiro ensaio mostraram que a RPD aumentou a GIM mas diminuiu a performance produtiva nos suínos comerciais cruzados, mas não nos Alentejanos, o que sugere que a restrição em lisina medeia o efeito da RPD na deposição lipídica no músculo. O efeito da RPD na GIM nos suínos cruzados foi acompanhado pelo aumento dos níveis de mRNA da delta 9 desaturase (SCD) e PPARγ. A espessura do toucinho não alterou com a RPD, mas aumentaram os ácidos gordos totais nos dois genótipos. Além disso, este resultado reflecte uma tendência para maiores scores sensoriais nos suínos cruzados. Os suínos Alentejanos mostraram maiores scores sensoriais do que os suínos cruzados, apesar da dieta RPD ter aumentado a suculência nos suínos cruzados. No segundo ensaio experimental, a dieta reduzida em proteína aumentou a GIM e a espessura do toucinho. Contudo, o aumento da GIM foi também acompanhado com o aumento da expressão da SCD, mas não melhorou as características sensoriais da carne. Nem a suplementação da dieta com arginina nem com leucina aumentaram o teor de GIM. Porém, a arginina introduziu off-flavor na carne. O único efeito relevante da arginina foi o aumento do teor de gordura no tecido adiposo subcutâneo (consistente com o aumento da expressão dos genes da sintese de ácidos gordos (FASN e SCD) e um pequeno decréscimo do 20:5n-3 e do total de n-3 PUFA no músculo. A suplementação com leucina resultou no aumento de expressão da SCD e FASN no músculo, reflectida num aumento das proporções de 18:1c9 e 16:0 e da diminuição dos teores de PUFA. Os resultados sugerem que a partição da gordura pode ser modulada e a qualidade sensorial da carne de suíno melhorada com dietas com teor de proteína reduzido sem ajustamento da lisina.
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Jerónimo, Eliana Alexandra Sousa. "Dietary manipulation to inprove the nutritional value of lipids from lamb meat." Doctoral thesis, Universidade de Évora, 2011. http://hdl.handle.net/10174/15306.
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A carne de borrego é caracterizada por altos teores em ácidos gordos (AG) saturados e baixos níveis de ácidos gordos polinsaturados (AGPI), propriedades que são consideradas prejudicais para a saúde humana. Para atender às recomendações nutricionais é necessário melhorar a sua composição em AG. A principal motivação desta tese foi explorar algumas estratégias nutricionais que permitam melhorar o valor nutricional da fracção lipídica da carne de borrego. Os resultados obtidos mostram que a suplementação das dietas com óleos vegetais ricos em AGPI é uma abordagem eficaz para reduzir a saturação da carne de borrego e aumentar o seu conteúdo em AGPI. Além disso, a suplementação com mistura de óleos de girassol e de linho permitiu aumentar simultaneamente o conteúdo em isómeros conjugados do ácido linoleico e em AGPI n-3 de cadeia longa. A inclusão de bentonite sódica e de Cistus ladanifer em dietas suplementadas com óleo também mostrou ser uma boa abordagem para melhorar a composição em AG da carne de borrego; ABSTRACT:
Dietary manipulation to improve the nutritional value of lipids from lamb meat
Lamb meat is characterized by high contents of saturated fatty acids and low levels of polyunsaturated fatty acids (PUFA), properties that are regarded as being negative to human health. To meet the nutritional recommendations is necessary improving the fatty acid (FA) composition of lamb meat. The main motivation of this thesis was explored some nutritional strategies that allows improve the nutritional value of lipid fraction from lamb meat. Data presented here show that supplementation of diets with vegetable oils rich in PUFA is an effective approach to decrease the saturation of lamb meat and increase its content in PUFA. Moreover, supplementation with blend of sunflower and linseed oils allowed increase simultaneously meat content in conjugated isomers of linoleic acid and n-3 long chain PUFA. Inclusion of sodium bentonite and Cistus ladanifer in oil supplemented diets also showed to be a good approach to improve the FA composition of lamb meat.
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Sutherland, Sarah C. "Characteristics Associated with Neonatal Carnitine Levels: A Systematic Review & Clinical Database Analysis." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/23744.
Full textAbstract:
Newborn screening programs measure analyte levels in neonatal blood spots to identify individuals at high risk of disease. Carnitine and acylcarnitine levels are primary markers used in the detection of fatty acid oxidation disorders. These analytes may be influenced by certain pre/perinatal or newborn screening related factors. The primary objective of this study was to explore the association between these characteristics and levels of blood carnitines and acylcarnitines in the newborn population. The study was composed of two parts: a systematic review and a clinical database analysis of existing newborn screening data. The systematic review results suggested considerable variability across studies in the presence and directionality of associations between analyte levels and birth weight, gestational age, age at time of blood spot collection, type of sample, and storage time. Sex was not significantly associated with carnitine or acylcarnitine levels in neonatal blood. We identified a need to more fully investigate a potential interaction between gestational age and birth weight in regard to analyte levels. The secondary data analyses indicated a statistically significant relationship between analyte levels and all perinatal / infant and newborn screening related factors of interest, but effect sizes were generally small. The interaction between gestational age and birth weight was significant in all models; when further explored through graphical analysis with conditional means, extremely premature neonates stood out as having distinct analyte patterns in relation to birth weight. Variation in the ratio of total acylcarnitine to free carnitine was better accounted for by the perinatal and newborn factors than was variation in any individual carnitine or acylcarnitine, indicating that proportions of carnitine and acylcarnitines may be more important in understanding an individual’s metabolic functioning than individual analyte levels. A low proportion of variation was explained in all multivariate models, supporting the use of universal algorithms in newborn screening and suggesting the need for further large scale empirical research targeted at previously unaccounted for perinatal factors such as birth stress.
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El, Kebbaj Riad. "Base moléculaire des effets de l'huile d'argan sur le métabolisme mitochondrial et peroxysomal des acides gras et sur l'inflammation." Phd thesis, Université de Bourgogne, 2012. http://tel.archives-ouvertes.fr/tel-01015507.
Full textAbstract:
L'objectif des travaux de cette thèse a été d'explorer les bases moléculaires de l'effet de l'huile d'Argan (HA) sur le métabolisme lipidique au niveau mitochondriale et peroxysomale ainsi qu'élucider son potentiel anti-inflammatoire. Nous avons donc montré, dans un premier temps, que les méthodes artisanales préservaient les propriétés antioxydantes d'HA empêchant l'oxydation de l'acide férulique contrairement à l'HA d'origines commerciale. Ensuite, le traitement par l'HA ou par les lipopolysaccharides (LPS) de fibroblastes humains, un modèle cellulaire de la pseudo-adrénoleucodystrophie néonatale (P-NALD), révèle pour l'HA une prolifération des peroxysomes indépendante de l'activation du récepteur nucléaire PPARα et de son coactivateur PGC-1α. Par contre, l'induction de la prolifération de peroxysomes par les LPS est accompagnée d'une activation de PPAR et de PGC-1Parallèlement, une étude a été réalisée au niveau hépatique chez des souris traitées par l'HA ou par les LPS. Nous avons montré pour la première fois l'activité antioxydante de l'huile d'Argan in vivo au niveau hépatique par l'induction de l'activité enzymatique de la catalase peroxysomale et une activité hypolipémiante par la stimulation des activités déshydrogénases (ACADs) de la -oxydations mitochondriale des acides gars. De plus, l'HA induit la transcription des gènes PPECK et G6PH de la voie de la néoglucogenèse. Nous avons montré également pour la première fois un effet préventif de l'HA contre la répression des activités déshydrogénases des voies de -oxydations mitochondriale et peroxysomale, ainsi que celle la voie de la néoglucogenèse. Nos travaux démontrent que l'HA possède un potentiel anti-inflammatoire, induit par le LPS, élucidé par la répression de cytokines pro-inflammatoires IL-6 et TNFα et par l'induction de cytokines anti-inflammatoires IL10 et IL-4. L'ensemble de nos résultats indiquerait que l'huile d'Argan, du fait de sa composition riche en acide gras mono et polyinsaturés et en antioxydants, a des effets hypolipémiants et anti-inflammatoires au niveau hépatique qui se traduisent par une régulation de l'expression à la fois de récepteurs nucléaires et de leur gènes cibles ainsi que de certaines cytokines