Academic literature on the topic 'Glycerides Metabolism'

Abstract: Drug-lipid conjugates have been prepared in order to confer the attached drugs to the metabolic pathways of natural lipids. The drug can be covalently bound either to a fatty acid or to a glyceride. In glycerides, one or two fatty acid moieties have been replaced by a drug realizing pseudoglycerides. These pseudoglycerides exhibited some physicochemi­ cal properties and absorption characteristics similar to those of natural triglycerides resulting in a different pharmacokinetic and/or pharmacodynamic profile compared that of the parent drug. Non-steroidal anti-inflammatory drugs such as aspirin, indomethacin, ibuprofen, naproxen and aclofenac were covalently bound to diglycerides in order to reduce the ulcerogenicity of the compounds. Employing the absorption process of dietary fat, pseudoglycerides have been used for the targeting of the lymphatic route in order to avoid the first-pass metabolism of a drug (L-DOPA) and I or to target the lymphatic system for the treatment of lymphatic metastasis (chlorambucil, melphalan) or filiariasis (melphalan and GABA). Pseudoglycerides and other glyceride-like structures have been evaluated in order to increase the intestinal absorption of poorly water-soluble drugs such as phenytoin. An improvement of the blood-brain barrier penetration of GABA covalently bound to glycerides has been reported in the 80's, A similar approach was followed for L-dopa, glycine, valproate, and the enkephalinase inhibitor thiorphan including amide bio-isosteres of glycerides. Radioiodinated agents containing fluoride and nitroxyl moieties were coupled to glycerides and fatty acids as potential hepatographic agents in nuclear medicine, 19F- and 1H-nuclear magnetic resonance imaging, respectively. A variety of phospholipid-linked cytotoxic nucleosides and nucleoside analogues such as ara-C, AZT and acyclovir have been prepared. Compared to the parent drugs the phospholipid analogs exhibited increased antineoplastic activity in vitro and in vivo. The conjugates were also active against tumors and viruses that were resistant against the drug itself.

The excessive accumulation of lipids in hepatocytes induces a type of cytotoxicity called hepatic lipotoxicity, which is a fundamental contributor to liver metabolic diseases (such as NAFLD). Magnesium isoglycyrrhizinate (MGIG), a magnesium salt of the stereoisomer of natural glycyrrhizic acid, is widely used as a safe and effective liver protectant. However, the mechanism by which MGIG protects against NAFLD remains unknown. Based on the significant correlation between NAFLD and the reprogramming of liver metabolism, we aimed to explore the beneficial effects of MGIG from a metabolic viewpoint in this paper. We treated HepaRG cells with palmitic acid (PA, a saturated fatty acid of C16:0) to induce lipotoxicity and then evaluated the antagonistic effect of MGIG on lipotoxicity by investigating the cell survival rate, DNA proliferation rate, organelle damage, and endoplasmic reticulum stress (ERS). Metabolomics, lipidomics, and isotope tracing were used to investigate changes in the metabolite profile, lipid profile, and lipid flux in HepaRG cells under different intervention conditions. The results showed that MGIG can indeed protect hepatocytes against PA-induced cytotoxicity and ERS. In response to the metabolic abnormality of lipotoxicity, MGIG curtailed the metabolic activation of lipids induced by PA. The content of total lipids and saturated lipids containing C16:0 chains increased significantly after PA stimulation and then decreased significantly or even returned to normal levels after MGIG intervention. Lipidomic data show that glycerides and glycerophospholipids were the two most affected lipids. For excessive lipid accumulation in hepatocytes, MGIG can downregulate the expression of the metabolic enzymes (GPATs and DAGTs) involved in triglyceride biosynthesis. In conclusion, MGIG has a positive regulatory effect on the metabolic disorders that occur in hepatocytes under lipotoxicity, and the main mechanisms of this effect are in lipid metabolism, including reducing the total lipid content, reducing lipid saturation, inhibiting glyceride and glycerophospholipid metabolism, and downregulating the expression of metabolic enzymes in lipid synthesis.

Earthworms (Lumbricus terrestris) were given [1-14C]-labeled palmitic acid by gavage on days 0 and 3, and sacrificed on day 7. The distribution of label among lipid classes indicated that glycerides, sterol esters, cerebrosides, sulfatides, phosphatidylethanolamine, phosphatidylserine and (or) phosphatidylinositol, phosphatidylcholine, and sphingomyelin turn over in, or are synthesized by, the earthworm. Free fatty acids still had the highest specific radioactivity of any lipid class at the end of the experiment. Incorporation of label into sterol and hydrocarbon fractions was insignificant and there was no detectable label incorporated into gangliosides. Phosphatidylethanolamine apparently turned over quite slowly compared with other lipid classes, while the cerebroside fraction became highly labeled. Elongation of palmitic acid to stearate and oxidation to CO2 occurred extensively, but there was no evidence for desaturation.Key words: earthworm, Lumbricus, lipids, gangliosides, metabolism.

Background: White adipose tissue (WAT) browning confers beneficial effects on metabolic diseases. However, visceral adipose tissue (VAT) is not as susceptible to browning as subcutaneous adipose tissue (SAT). Aim: Interpreting the heterogeneity of VAT and SAT in brown remodeling and provide promising lipid targets to promote WAT browning. Methods: We first investigated the effects of β3-adrenergic stimulation by CL316,243 on systemic metabolism. Then, high-coverage targeted lipidomics approach with multiple reaction monitoring (MRM) was utilized to provide extensive detection of lipid metabolites in VAT and SAT. Results: CL316,243 notably ameliorated the systemic metabolism and induced brown remodeling of SAT but browning resistance of VAT. Comprehensive lipidomics analysis revealed browning heterogeneity of VAT and SAT with more dramatic alteration of lipid classes and species in VAT rather than SAT, though VAT is resistant to browning. Adrenergic stimulation differentially affected glycerides content in VAT and SAT and boosted the abundance of more glycerophospholipids species in VAT than in SAT. Besides, CL316,243 increased sphingolipids in VAT without changes in SAT, meanwhile, elevated cardiolipin species more prominently in VAT than in SAT. Conclusions: We demonstrated the browning heterogeneity of WAT and identified potential lipid biomarkers which may provide lipid targets for overcoming VAT browning resistance.

Adipose tissue plays a central role in energy substrate homeostasis and is a key regulator of lipid flow throughout these processes. As hypoxia affects lipid metabolism in adipose tissue, we aimed to investigate the effects of high-altitude chronic hypoxia on lipid metabolism in the adipose tissue of rats using a lipidomic analysis approach. Visceral adipose tissues from rats housed in a high-altitude hypoxia environment representing 4,300 m with 14.07% oxygen (hypoxia group) and from rats housed in a low-altitude normoxia environment representing 41 m with 20.95% oxygen (normoxia group) for 8 weeks were analyzed using an ultra-performance liquid chromatography-Orbitrap mass spectrometry system. After 8 weeks, the body weight and visceral adipose tissue weight of the hypoxia group were significantly decreased compared to those of the normoxia group (p < 0.05). The area and diameter of visceral adipose cells in the hypoxia group were significantly smaller than those of visceral adipose cells in the normoxia group (p < 0.05). The results of lipidomic analysis showed a total of 21 lipid classes and 819 lipid species. The total lipid concentration of the hypoxia group was lower than that in the normoxia group (p < 0.05). Concentrations of diacylglycerols and triacylglycerols in the hypoxia group were significantly lower than those in the normoxia group (p < 0.05). Using univariate and multivariate analyses, we identified 74 lipids that were significantly altered between the normoxia and hypoxia groups. These results demonstrate that high-altitude chronic hypoxia changes the metabolism of visceral adipose glycerides, which may potentially modulate other metabolic processes.

Cyperus esculentus is widely representing one of the important oil crops around the world, which provides valuable resources of edible tubers called tiger nut. The chemical composition and high ability to produce fats emphasize the role of tiger nut in promoting oil crop productivity. However, the underlying molecular mechanism of the production and accumulation of lipids in tiger nut development still remains unclear. Here, we conducted comprehensive transcriptomics and lipidomics analyses at different developmental stages of tuber in Cyperus esculentus. Lipidomic analyses confirmed that the accumulation of lipids including glycolipids, phospholipids, and glycerides were significantly enriched during tuber development from early to mature stage. The proportion of phosphatidylcholines (PC) declined during all stages and phosphatidyl ethanolamine (PE) was significantly declined in early and middle stages. These findings implied that PC is actively involved in triacylglycerol (TAG) biosynthesis during the tubers development, whereas PE may participate in TAG metabolism during early and middle stages. Comparative transcriptomics analyses indicated several genomic and metabolic pathways associated with lipid metabolism during tuber development in tiger nut. The Pearson correlation analysis showed that TAG synthesis in different developmental stages was attributed to 37 candidate transcripts including CePAH1. The up-regulation of diacylglycerol (DAG) and oil content in yeast, resulted from the inducible expression of exogenous CePAH1 confirmed the central role of this candidate gene in lipid metabolism. Our results demonstrated the foundation of an integrative metabolic model for understanding the molecular mechanism of tuber development in tiger nut, in which lipid biosynthesis plays a central role.

Background:This study aimed to examine combined and independent effects of cardiorespiratory fitness and fatness on cardiovascular risk factors among U.S. adolescents.Methods:Data from adolescents age 12 to 19 years participating in the NHANES 1999 to 2002 were used. Fitness level was determined by submaximal treadmill test and was dichotomized as ‘not fit’ or ‘fit’ according to the FITNESSGRAM. Fatness level was categorized as ‘not fat’ or ‘fat’ based on the CDC BMI growth charts. Gender-specific multivariable linear regression analyses were conducted to compare age-, race/ethnicity-, fatness-, and waist circumference-adjusted means of blood pressure, lipids, lipoproteins, C-peptide, insulin, and C-reactive protein (CRP) levels.Results:A total of 3202 adolescents (1629 boys) were included for data analysis. Among boys, total cholesterol, tri-glycerides, insulin, and CRP mean levels were significantly higher (P < .05) in the ‘not fit’ group than in the ‘fit’ group, after adjustment for fatness level and waist circumference. Among girls, the fatness level- and waist circumference-adjusted means of total cholesterol (P < .01) and LDL-C (P < .09) were higher in the ‘not fit’ than ‘fit’ groups.Conclusion:Cardiorespiratory fitness, independent of fatness, may have beneficial effects on lipid profiles among girls, and on lipid profiles, insulin metabolism, and inflammation levels among boys.

Les derniers apports nutritionnels conseillés recommandent une consommation plus importante en acides gras polyinsaturés de la série n-3 que celle actuellement constatée dans l’alimentation française. Dans ce contexte, il convenait d’appréhender les facteurs susceptibles de moduler l’absorption et le devenir de leur chef de file, l’ALA, en faisant appel à deux approches, l’une in vivo (rat), l’autre in vitro (Caco-2). L’étude relative au devenir métabolique de l’ALA, selon sa forme physique et chimique de présentation, a été réalisée avec des lipides « modèles » (TAG structurés) ou naturels (huile de lin) riches en ALA, et selon différents systèmes lipidiques (huile en phase continue ou en émulsion de type huile dans eau et de composition en phospholipides variables). Les résultats obtenus in vivo et in vitro à l’égard de l’huile de lin (émulsionnée ou non) montrent que l’émulsification accélère non seulement le passage intestinal de l’ALA mais améliore également sa concentration lymphatique. L’étude cellulaire a par ailleurs démontré que la présence de lysophospholipides dans les micelles mixtes permet d’améliorer la sécrétion de l’ALA dans les lipoprotéines. D’autre part, le devenir métabolique de l’ALA dépend de sa régiolocalisation sur le triglycéride alimentaire. En effet, les résultats de l’étude faisant appel aux TAG structurés montrent que la position interne n’est que partiellement conservée dans la lymphe, suggérant qu’une hydrolyse des 2-MAG serait opérée par une MG lipase. En conséquence, l’ensemble des résultats obtenus lors de cette étude montre que l’absorption et le transport de l’ALA seraient uniquement modulés selon la forme physique de l’acide gras alors que son devenir et son utilisation métabolique dépendraient de sa régiolocalisation sur le TAG alimentaire. Ces deux facteurs réunis permettraient dés lors de prévenir l’ALA d’une β-oxydation précoce, en vue de favoriser son élongation en dérivés supérieurs dans les tissus cibles
The last recommended nutrient intakes advise a higher consumption of n-3 polyunsaturated fatty acids series than currently found in French diet. In this context, it was appropriate to apprehend the factors that could modulate the absorption and fate of their leader, ALA, using two approaches, one in vivo (rat), the other one in vitro (Caco-2). The study on the metabolic fate of ALA, according to its physical and chemical submission form, was conducted with "models" lipids (structured TAG) or natural (flaxseed oil) rich in ALA, and according to different lipid systems (oil in continuous phase or in emulsion type oil in water and with variable phospholipid composition). Results obtained in vivo and in vitro for flaxseed oil (emulsion or not) show that emulsification enhances the recovery of ALA at the intestinal level but also improves its lymphatic concentration. The cell study also demonstrated that the presence of lysophospholipids in mixed micelles can improve the secretion of ALA in lipoproteins. On the other hand, the metabolic fate of ALA depends on its location on the glycerol backbone of the dietary triglyceride. The results of the study using structured TAG show that the internal position is partially preserved in lymph, suggesting that a hydrolysis of 2 - MAG by MG lipase could occur. Accordingly, all of the results obtained in this study shows that the absorption and transport of ALA would only be modulated according to the physical form of the fatty acid while its fate and its metabolic use would depend on its location on the dietary TAG. These two factors combined would then allow preventing the early β-oxidation of ALA in order to promote its elongation in higher derivatives in the target tissues