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1

Song, Jae-Eun, Tiago C. Alves, Bernardo Stutz, Matija Šestan-Peša, Nicole Kilian, Sungho Jin, Sabrina Diano, Richard G. Kibbey e Tamas L. Horvath. "Mitochondrial Fission Governed by Drp1 Regulates Exogenous Fatty Acid Usage and Storage in Hela Cells". Metabolites 11, n. 5 (18 maggio 2021): 322. http://dx.doi.org/10.3390/metabo11050322.

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Abstract (sommario):
In the presence of high abundance of exogenous fatty acids, cells either store fatty acids in lipid droplets or oxidize them in mitochondria. In this study, we aimed to explore a novel and direct role of mitochondrial fission in lipid homeostasis in HeLa cells. We observed the association between mitochondrial morphology and lipid droplet accumulation in response to high exogenous fatty acids. We inhibited mitochondrial fission by silencing dynamin-related protein 1(DRP1) and observed the shift in fatty acid storage-usage balance. Inhibition of mitochondrial fission resulted in an increase in fatty acid content of lipid droplets and a decrease in mitochondrial fatty acid oxidation. Next, we overexpressed carnitine palmitoyltransferase-1 (CPT1), a key mitochondrial protein in fatty acid oxidation, to further examine the relationship between mitochondrial fatty acid usage and mitochondrial morphology. Mitochondrial fission plays a role in distributing exogenous fatty acids. CPT1A controlled the respiratory rate of mitochondrial fatty acid oxidation but did not cause a shift in the distribution of fatty acids between mitochondria and lipid droplets. Our data reveals a novel function for mitochondrial fission in balancing exogenous fatty acids between usage and storage, assigning a role for mitochondrial dynamics in control of intracellular fuel utilization and partitioning.
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2

Peters-Golden, M., e C. Shelly. "Inhibitory effect of exogenous arachidonic acid on alveolar macrophage 5-lipoxygenase metabolism. Role of ATP depletion." Journal of Immunology 140, n. 6 (15 marzo 1988): 1958–66. http://dx.doi.org/10.4049/jimmunol.140.6.1958.

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Abstract (sommario):
Abstract Although a variety of agonists have the capacity to stimulate the release of endogenous arachidonic acid (AA) from macrophage lipids and its subsequent metabolism to both cyclooxygenase and 5-lipoxygenase eicosanoids, including leukotrienes (LT), previous work suggests that exogenously supplied arachidonate is metabolized preferentially to cyclooxygenase products and mono-hydroxyeicosatetranenoic acids rather than LT. We have compared the metabolism of endogenous and exogenous AA in cultured rat alveolar macrophages and have further examined the effect of exogenous fatty acids on eicosanoid synthesis stimulated by the calcium ionophore A23187 and the particulate agonist zymosan. As reported by others, exogenous AA was metabolized to large amounts of cyclooxygenase products, 12-hydroxyeicosatetraenoic acid and 15-hydroxyeicosatetraenoic acid, but far lesser amounts of all 5-lipoxygenase products. However, whereas exogenous AA augmented the synthesis of cyclooxygenase metabolites in both A23187- and zymosan-stimulated cells, it dose-dependently inhibited the synthesis of LT. Inasmuch as unsaturated fatty acids, including AA, uncouple oxidative phosphorylation, and because 5-lipoxygenase activity depends on ATP, we examined the possibility that ATP depletion was responsible for the inhibition of LT synthesis by exogenous AA. Arachidonate depleted cellular ATP in a dose-dependent fashion similar to its inhibition of LT synthesis. In addition, the other unsaturated fatty acids, linolenic and eicosatrienoic, but not the saturated fatty acids, palmitic or stearic, both depleted ATP and inhibited A23187-induced LT synthesis. These data suggest that the relative lack of synthesis of LT from exogenous AA is related to the ability of this unsaturated fatty acid to function as an inhibitor, as well as a substrate, of 5-lipoxygenase. Our results further suggest that this inhibition of 5-lipoxygenase may be mediated by ATP depletion.
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3

Desfougères, Thomas, Thierry Ferreira, Thierry Bergès e Matthieu Régnacq. "SFH2 regulates fatty acid synthase activity in the yeast Saccharomyces cerevisiae and is critical to prevent saturated fatty acid accumulation in response to haem and oleic acid depletion". Biochemical Journal 409, n. 1 (11 dicembre 2007): 299–309. http://dx.doi.org/10.1042/bj20071028.

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Abstract (sommario):
The yeast Saccharomyces cerevisiae is a facultative anaerobic organism. Under anaerobiosis, sustained growth relies on the presence of exogenously supplied unsaturated fatty acids and ergosterol that yeast is unable to synthesize in the absence of oxygen or upon haem depletion. In the absence of exogenous supplementation with unsaturated fatty acid, a net accumulation of SFA (saturated fatty acid) is observed that induces significant modification of phospholipid profile [Ferreira, Régnacq, Alimardani, Moreau-Vauzelle and Bergès (2004) Biochem. J. 378, 899–908]. In the present paper, we focus on the role of SFH2/CSR1, a hypoxic gene related to SEC14 and its involvement in lipid metabolism upon haem depletion in the absence of oleic acid supplementation. We observed that inactivation of SFH2 results in enhanced accumulation of SFA and phospholipid metabolism alterations. It results in premature growth arrest and leads to an exacerbated sensitivity to exogenous SFA. This phenotype is suppressed in the presence of exogenous oleic acid, or by a controlled expression of FAS1, one of the two genes encoding FAS. We present several lines of evidence to suggest that Sfh2p and oleic acid regulate SFA synthase in yeast at different levels: whereas oleic acid acts on FAS2 at the transcriptional level, we show that Sfh2p inhibits fatty acid synthase activity in response to haem depletion.
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4

Yao, Jiangwei, e Charles O. Rock. "Exogenous fatty acid metabolism in bacteria". Biochimie 141 (ottobre 2017): 30–39. http://dx.doi.org/10.1016/j.biochi.2017.06.015.

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5

Mahajan, Sandeep, e G. K. Khuller. "Cerulenin inhibition of lipid synthesis and its reversal by exogenous fatty acids in Mycobacterium smegmatis ATCC 607". Canadian Journal of Biochemistry and Cell Biology 63, n. 2 (1 febbraio 1985): 85–90. http://dx.doi.org/10.1139/o85-012.

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Abstract (sommario):
Cerulenin inhibited the lipid synthesis of Mycobacterium smegmatis ATCC 607 over the range of 0.5–1.8 μg/mL with complete inhibition at 1.8 μg/mL, as monitored by [14C]glycerol incorporation into lipids. Exogenous fatty acids failed to restore the lipid synthesis at 1.8 μg/mL; however, the addition of palmitic acid to the growth medium partially restored the lipid synthesis when cerulenin concentration was decreased to 1.6 μg/mL. Fatty acid analysis of cerulenin plus palmitic acid supplemented cultures revealed that exogenously supplied fatty acid was incorporated into cellular phospholipids. Further investigations with 1.6 μg/mL of cerulenin and [14C]acetate and [32P]orthophosphoric acid showed that cerulenin inhibited the synthesis of saturated plus unsaturated fatty acids and phospholipids. Pulse–chase studies with [14C]acetate revealed decreased synthesis and degradation of each of the phospholipid components.
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6

Saito, Holly E., John R. Harp e Elizabeth M. Fozo. "Incorporation of Exogenous Fatty Acids Protects Enterococcus faecalis from Membrane-Damaging Agents". Applied and Environmental Microbiology 80, n. 20 (15 agosto 2014): 6527–38. http://dx.doi.org/10.1128/aem.02044-14.

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ABSTRACTEnterococcus faecalisis a commensal bacterium of the mammalian intestine that can persist in soil and aquatic systems and can be a nosocomial pathogen to humans. It employs multiple stress adaptation strategies in order to survive such a wide range of environments. Within this study, we sought to elucidate whether membrane fatty acid composition changes are an important component for stress adaptation. We noted thatE. faecalisOG1RF was capable of changing its membrane composition depending upon growth phase and temperature. The organism also readily incorporated fatty acids from bile, serum, and medium supplemented with individual fatty acids, often dramatically changing the membrane composition such that a single fatty acid was predominant. Growth in either low levels of bile or specific individual fatty acids was found to protect the organism from membrane challenges such as high bile exposure. In particular, we observed that when grown in low levels of bile, serum, or the host-derived fatty acids oleic acid and linoleic acid,E. faecaliswas better able to survive the antibiotic daptomycin. Interestingly, the degree of membrane saturation did not appear to be important for protection from the stressors examined here; instead, it appears that a specific fatty acid or combination of fatty acids is critical for stress resistance.
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7

Gibbons, G. F., e F. J. Burnham. "Effect of nutritional state on the utilization of fatty acids for hepatitic triacylglycerol synthesis and secretion as very-low-density lipoprotein". Biochemical Journal 275, n. 1 (1 aprile 1991): 87–92. http://dx.doi.org/10.1042/bj2750087.

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Abstract (sommario):
The mass of very-low-density-lipoproteins (VLDL) triacylglycerol secreted from isolated hepatocytes was dependent on the nutritional state of the donor rats, and declined in the order sucrose-fed greater than chow-fed greater than polyunsaturated-fat-fed greater than starved. This was the case irrespective of the presence or absence of exogenous oleate. The contribution of newly synthesized fatty acids to the total mass of VLDL triacylglycerol also declined in the above order, and reflected the relative rates of fatty acid synthesis de novo in each of the groups. The contribution of exogenous oleate to VLDL triacylglycerol varied in a manner similar to that for newly synthesized fatty acid. However, the contribution either of exogenous oleate or of newly synthesized fatty acid never exceeded 17-20% of the total VLDL triacylglycerol fatty acid even in the sucrose-fed animals. The increased contribution of newly synthesized fatty acids in the sucrose-fed group was not sufficient to account for the increase in the total mass of VLDL triacylglycerol secreted. These results suggest that: (a) changes in the rate of triacylglycerol secretion are not a direct consequence of variations in the rate of fatty acid synthesis de novo; (b) in the short term, most of the triacylglycerol required for VLDL assembly and secretion is derived from an intracellular storage source: (c) the distribution of newly synthesized triacylglycerol between the cytosolic and secretory pools was similar irrespective of the source of fatty acids (i.e. synthesized de novo or exogenous).
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8

Black, Paul N., e Concetta C. DiRusso. "Transmembrane Movement of Exogenous Long-Chain Fatty Acids: Proteins, Enzymes, and Vectorial Esterification". Microbiology and Molecular Biology Reviews 67, n. 3 (settembre 2003): 454–72. http://dx.doi.org/10.1128/mmbr.67.3.454-472.2003.

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Abstract (sommario):
SUMMARY The processes that govern the regulated transport of long-chain fatty acids across the plasma membrane are quite distinct compared to counterparts involved in the transport of hydrophilic solutes such as sugars and amino acids. These differences stem from the unique physical and chemical properties of long-chain fatty acids. To date, several distinct classes of proteins have been shown to participate in the transport of exogenous long-chain fatty acids across the membrane. More recent work is consistent with the hypothesis that in addition to the role played by proteins in this process, there is a diffusional component which must also be considered. Central to the development of this hypothesis are the appropriate experimental systems, which can be manipulated using the tools of molecular genetics. Escherichia coli and Saccharomyces cerevisiae are ideally suited as model systems to study this process in that both (i) exhibit saturable long-chain fatty acid transport at low ligand concentrations, (ii) have specific membrane-bound and membrane-associated proteins that are components of the transport apparatus, and (iii) can be easily manipulated using the tools of molecular genetics. In both systems, central players in the process of fatty acid transport are fatty acid transport proteins (FadL or Fat1p) and fatty acyl coenzyme A (CoA) synthetase (FACS; fatty acid CoA ligase [AMP forming] [EC 6.2.1.3]). FACS appears to function in concert with FadL (bacteria) or Fat1p (yeast) in the conversion of the free fatty acid to CoA thioesters concomitant with transport, thereby rendering this process unidirectional. This process of trapping transported fatty acids represents one fundamental mechanism operational in the transport of exogenous fatty acids.
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9

Yamasaki, Tomohiro, Lumin Zhang, Tyrone Dowdy, Adrian Lita, Kazuhiko Kurozumi e Mioara Larion. "TMET-15. THE COMBINATIONAL EFFECT OF INHIBITOR FOR A FATTY ACID DESATURASE AND A FATTY ACID TRANSPORTER ON GLIOMA GROWTH". Neuro-Oncology 25, Supplement_5 (1 novembre 2023): v275—v276. http://dx.doi.org/10.1093/neuonc/noad179.1059.

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Abstract BACKGROUND It is not well understood how much exogenous fatty acids uptake and de novo fatty acid synthesis affect the cell proliferation in glioma. In this study, we examined the combinational effect of inhibitor for a fatty acid desaturase (SCD) and a fatty acid transporter (CD36) on glioma growth. METHODS Normal human astrocytes (NHA) were used as glial cells, and U251 transfected with IDH wild-type or IDH mutant gene and patient-derived glioma cells (BT142, TS603, GSC923S) were used as glioma cells. The function of SCD was suppressed by SCD inhibitor and SCD siRNA, and Sulfo-N-succinimidyl oleate (SSO) was used to inhibit the CD36 function. RESULTS We treated U251 cells with palmitic acid (C16:0), stearic acid (C18:0), palmitoleic acid (C16:1) or oleic acid (C18:1) after SCD inhibitors treatment or SCD knockdown, and cell proliferation was rescued only after the treatment with C16:1 and C18:1. NHA was not affected by SCD inhibitor, although CD36 inhibitor suppressed cell proliferation of both U251 and NHA. The combination of SCD inhibitor and CD36 inhibitor under the addition of exogenous fatty acid, oleic acid, suppressed the proliferation of U251 cells more effectively than SCD inhibitor or CD36 inhibitor alone. Discussion: The SCD inhibitory effect on gliomas was attenuated by the presence of exogenous monounsaturated fatty acids, whereas the CD36 inhibitor enhanced the cell-killing effect. On the other hand, it should be noted that CD36 inhibitors affect the proliferation of glial cells.
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10

Puteri Afiqah Abdul Wahab e Aziz Ahmad. "Effects of Exogenous Arachidonic Acid on Morphological Traits and Fatty Acid Profile of Rice (Oryza sativa L.) Grown on Saline Soil". Universiti Malaysia Terengganu Journal of Undergraduate Research 1, n. 3 (31 luglio 2019): 68–78. http://dx.doi.org/10.46754/umtjur.v1i3.80.

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Abstract (sommario):
Salinity is one of the major constraints in the rice production worldwide. Rice plants have moderate tolerance towards salinity. Salinity changes cell membrane permeability and fatty acid compositions by releasing the free fatty acids. Nonetheless, the effect of exogenous fatty acid such as arachidonic acid (AA) on rice grown on saline soil is yet unknown. The objective of the current study is to determine the effect of AA on the morphological traits and free fatty acids of rice plant grown under saline conditions. Rice plants grown on saline soil (EC=12 ds/m) were treated with 50 mM AA on day 45 after transplant. Leaves and panicles were sampled after two weeks of treatment and analysed for fatty acid profile using GC-MS. The morphological traits were observed at the maturity stage. Results showed that AA treatment improved the grain fill-in of the saline stress rice and reduced the accumulation of free fatty acids in the cell. The AA treatment also increased the linoleic acid (18:2), linolenic acid (18:3) in panicles and, dihomo-y-linolenic acid (20:3) and nervonic acid (24:1) in leaves. The finding suggests that exogenous AA regulates salinity stress in rice by reducing the accumulation of free fatty acids.
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11

Wetzels, J. F., X. Wang, P. E. Gengaro, R. A. Nemenoff, T. J. Burke e R. W. Schrier. "Glycine protection against hypoxic but not phospholipase A2-induced injury in rat proximal tubules". American Journal of Physiology-Renal Physiology 264, n. 1 (1 gennaio 1993): F94—F99. http://dx.doi.org/10.1152/ajprenal.1993.264.1.f94.

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Abstract (sommario):
We studied the effects of glycine (2 mM) on hypoxia-induced changes in phospholipids and fatty acids in isolated rat proximal tubules. In this preparation, 25 min of hypoxia caused cell injury, as reflected by the release of lactate dehydrogenase (LDH) (13.1 +/- 0.8 vs. 43.5 +/- 3.2%; P < 0.01). Hypoxia caused increases in fatty acids and in lysophospholipids. Glycine prevented the hypoxia-induced cell injury (LDH 13.1 +/- 0.8 vs. 11 +/- 0.7%; not significant) but did not attenuate the increases in fatty acids or lysophospholipids. In additional experiments, the effects of glycine on phospholipid changes and cell injury induced by exogenous phospholipase A2 (PLA2) were studied. PLA2 caused dramatic increases in fatty acids and lysophospholipids and mild cell injury; these effects were not influenced by glycine. In contrast, glycine attenuated increases in LDH release induced by exposing the tubules to exogenous arachidonic acid. In conclusion, glycine does not prevent the phospholipid degradation induced by either exogenous PLA2 or hypoxia in isolated proximal tubules and yet affords protection against hypoxia and exogenous arachidonic acid.
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12

Ceddia, RB, e R. Curi. "Leptin controls the fate of fatty acids in isolated rat white adipocytes". Journal of Endocrinology 175, n. 3 (1 dicembre 2002): 735–44. http://dx.doi.org/10.1677/joe.0.1750735.

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Abstract (sommario):
Leptin directly increases the rate of exogenous glucose and fatty acids oxidation in isolated adipocytes. However, the effects of leptin on fatty acid metabolism in white adipose tIssue have not been examined in detail. Here, we report that in adipocytes incubated for 6 h in the presence of leptin (10 ng/ml), the insulin-stimulated de novo fatty acid synthesis was inhibited by 36% (P<0.05), while the exogenous oxidation of acetic and oleic acids was increased by 50% and 76% respectively. Interestingly, leptin did not alter the oxidation of intracellular fatty acids. Leptin-incubated cells presented a 16-fold increase in the incorporation of oleic acid into triglyceride (TG) and a 123% increase in the intracellular TG hydrolysis (as measured by free fatty acids release). Fatty acid-TG cycling was not affected by leptin. By employing fatty acids radiolabeled with (3)H and (14)C, we could determine the concomitant influx of fatty acids (incorporation of fatty acids into TG) and efflux of fatty acids (intracellular fatty acids oxidation and free fatty acids release) in the incubated cells. Leptin increased by 30% the net efflux of fatty acids from adipocytes. We conclude that leptin directly inhibits de novo synthesis of fatty acids and increases the release and oxidation of fatty acids in isolated rat adipocytes. These direct energy-dissipating effects of leptin may play an important role in reducing accumulation of fatty acids into TG of rat adipose cells.
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13

Green, Charlotte J., Deborah Johnson, Harsh D. Amin, Pamela Sivathondan, Michael A. Silva, Lai Mun Wang, Lara Stevanato et al. "Characterization of lipid metabolism in a novel immortalized human hepatocyte cell line". American Journal of Physiology-Endocrinology and Metabolism 309, n. 6 (15 settembre 2015): E511—E522. http://dx.doi.org/10.1152/ajpendo.00594.2014.

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Abstract (sommario):
The development of hepatocyte cell models that represent fatty acid partitioning within the human liver would be beneficial for the study of the development and progression of nonalcoholic fatty liver disease (NAFLD). We sought to develop and characterize a novel human liver cell line (LIV0APOLY) to establish a model of lipid accumulation using a physiological mixture of fatty acids under low- and high-glucose conditions. LIV0APOLY cells were compared with a well-established cell line (HepG2) and, where possible, primary human hepatocytes. LIV0APOLY cells were found to proliferate and express some mature liver markers and were wild type for the PNPLA3 (rs738409) gene, whereas HepG2 cells carried the Ile148Met variant that is positively associated with liver fat content. Intracellular triglyceride content was higher in HepG2 than in LIV0APOLY cells; exposure to high glucose and/or exogenous fatty acids increased intracellular triglyceride in both cell lines. Triglyceride concentrations in media were higher from LIV0APOLY compared with HepG2 cells. Culturing LIV0APOLY cells in high glucose increased a marker of endoplasmic reticulum stress and attenuated insulin-stimulated Akt phosphorylation whereas low glucose and exogenous fatty acids increased AMPK phosphorylation. Although LIV0APOLY cells and primary hepatocytes stored similar amounts of exogenous fatty acids as triglyceride, more exogenous fatty acids were partitioned toward oxidation in the LIV0APOLY cells than in primary hepatocytes. LIV0APOLY cells offer the potential to be a renewable cellular model for studying the effects of exogenous metabolic substrates on fatty acid partitioning; however, their usefulness as a model of lipoprotein metabolism needs to be further explored.
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14

Yazawa, Hisashi, Hitoshi Iwahashi, Yasushi Kamisaka, Kazuyoshi Kimura, Tsunehiro Aki, Kazuhisa Ono e Hiroshi Uemura. "Heterologous Production of Dihomo-γ-Linolenic Acid in Saccharomyces cerevisiae". Applied and Environmental Microbiology 73, n. 21 (14 settembre 2007): 6965–71. http://dx.doi.org/10.1128/aem.01008-07.

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Abstract (sommario):
ABSTRACT To make dihomo-γ-linolenic acid (DGLA) (20:3n-6) in Saccharomyces cerevisiae, we introduced Kluyveromyces lactis Δ12 fatty acid desaturase, rat Δ6 fatty acid desaturase, and rat elongase genes. Because Fad2p is able to convert the endogenous oleic acid to linoleic acid, this allowed DGLA biosynthesis without the need to supply exogenous fatty acids on the media. Medium composition, cultivation temperature, and incubation time were examined to improve the yield of DGLA. Fatty acid content was increased by changing the medium from a standard synthetic dropout medium to a nitrogen-limited minimal medium (NSD). Production of DGLA was higher in the cells grown at 15�C than in those grown at 20�C, and no DGLA production was observed in the cells grown at 30�C. In NSD at 15�C, fatty acid content increased up until day 7 and decreased after day 10. When the cells were grown in NSD for 7 days at 15�C, the yield of DGLA reached 2.19 μg/mg of cells (dry weight) and the composition of DGLA to total fatty acids was 2.74%. To our knowledge, this is the first report describing the production of polyunsaturated fatty acids in S. cerevisiae without supplying the exogenous fatty acids.
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15

Wu, Wei-Jia, Ying-Ning Zou, Zhi-Yan Xiao, Fang-Ling Wang, Abeer Hashem, Elsayed Fathi Abd_Allah e Qiang-Sheng Wu. "Changes in Fatty Acid Profiles in Seeds of Camellia oleifera Treated by Mycorrhizal Fungi and Glomalin". Horticulturae 10, n. 6 (2 giugno 2024): 580. http://dx.doi.org/10.3390/horticulturae10060580.

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Abstract (sommario):
Camellia oleifera is an important oilseed forest tree, but it is unknown whether and how inoculation with arbuscular mycorrhizal fungi, as well as spraying easily extractable glomalin-related soil protein (EG), regulates the fatty acid profile in seeds of this species. This study explored how inoculation with Rhizophagus intraradices (800 g inoculum/tree) and spraying EG (2.5 L/tree, four times in total, once a week) modulated the fatty acid profile for potential nutritional qualities in the seeds of 20-year-old C. oleifera. Spraying exogenous EG significantly increased fruit transverse diameter, longitudinal diameter, fruit weight, number of seeds, and seed weight but had no significant effect on the root mycorrhizal colonization rate. Inoculation with R. intraradices had no significant effect on these fruit traits but significantly boosted the root mycorrhizal colonization rate. A total of 11 saturated fatty acids and 12 unsaturated fatty acids were detected from the seeds, with the unsaturated fatty acids consisting primarily of C18:1N-12, C18:1N-9C, and C18:2-N6. Spraying exogenous EG significantly increased the levels of major unsaturated fatty acid components such as C18:1N-12, C18:1N-9C, C18:1N-7, and C18:2N-6 by 140.6%, 59.7%, 97.6%, and 60.6%, respectively, while decreasing the level of C16:0. Inoculation with R. intraradices only decreased the levels of C16:0 and C18:0, while increased the level of C18:2N-6. Both treatments increased the percentage of unsaturated fatty acids in total fatty acids, resulting in an increase in the unsaturation index of fatty acids. In addition, inoculation with R. intraradices significantly up-regulated the expression of CoFAD2, spraying exogenous EG significantly increased the expression of CoSAD, CoFAD2, and CoFAD3, and both treatments also significantly suppressed the expression of CoFAE. These findings suggested that exogenous EG as a biostimulant, is more suitable to regulate the nutritional values of fatty acids in seeds of 20-year-old C. oleifera.
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Longnus, Sarah L., Richard B. Wambolt, Rick L. Barr, Gary D. Lopaschuk e Michael F. Allard. "Regulation of myocardial fatty acid oxidation by substrate supply". American Journal of Physiology-Heart and Circulatory Physiology 281, n. 4 (1 ottobre 2001): H1561—H1567. http://dx.doi.org/10.1152/ajpheart.2001.281.4.h1561.

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Abstract (sommario):
We tested the hypothesis that myocardial substrate supply regulates fatty acid oxidation independent of changes in acetyl-CoA carboxylase (ACC) and 5′-AMP-activated protein kinase (AMPK) activities. Fatty acid oxidation was measured in isolated working rat hearts exposed to different concentrations of exogenous long-chain (0.4 or 1.2 mM palmitate) or medium-chain (0.6 or 2.4 mM octanoate) fatty acids. Fatty acid oxidation was increased with increasing exogenous substrate concentration in both palmitate and octanoate groups. Malonyl-CoA content only rose as acetyl-CoA supply from octanoate oxidation increased. The increases in octanoate oxidation and malonyl-CoA content were independent of changes in ACC and AMPK activity, except that ACC activity increased with very high acetyl-CoA supply levels. Our data suggest that myocardial substrate supply is the primary mechanism responsible for alterations in fatty acid oxidation rates under nonstressful conditions and when substrates are present at physiological concentrations. More extreme variations in substrate supply lead to changes in fatty acid oxidation by the additional involvement of intracellular regulatory pathways.
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Cropp, T. Ashton, Adam A. Smogowicz, Edmund W. Hafner, Claudio D. Denoya, Hamish AI McArthur e Kevin A. Reynolds. "Fatty-acid biosynthesis in a branched-chain α-keto acid dehydrogenase mutant ofStreptomyces avermitilis". Canadian Journal of Microbiology 46, n. 6 (1 giugno 2000): 506–14. http://dx.doi.org/10.1139/w00-028.

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Abstract (sommario):
Fatty-acid biosynthesis by a branched-chain alpha-keto acid dehydrogenase (bkd) mutant of Streptomyces avermitilis was analyzed. This mutant is unable to produce the appropriate precursors of branched-chain fatty acid (BCFA) biosynthesis, but unlike the comparable Bacillus subtilis mutant, was shown not to have an obligate growth requirement for these precursors. The bkd mutant produced only straight-chain fatty acids (SCFAs) with membrane fluidity provided entirely by unsaturated fatty acids (UFAs), the levels of which increased dramatically compared to the wild-type strain. The levels of UFAs increased in both the wild-type and bkd mutant strains as the growth temperature was lowered from 37°C to 24°C, suggesting that a regulatory mechanism exists to alter the proportion of UFAs in response either to a loss of BCFA biosynthesis, or a decreased growth temperature. No evidence of a regulatory mechanism for BCFAs was observed, as the types of these fatty acids, which contribute significantly to membrane fluidity, did not alter when the wild-type S. avermitilis was grown at different temperatures. The principal UFA produced by S. avermitilis was shown to be delta9-hexadecenoate, the same fatty acid produced by Escherichia coli. This observation, and the inability of S. avermitilis to convert exogenous labeled palmitate to the corresponding UFA, was shown to be consistent with an anaerobic pathway for UFA biosynthesis. Incorporation studies with theS. avermitilis bkd mutant demonstrated that the fatty acid synthase has a remarkably broad substrate specificity and is able to process a wide range of exogenous branched chain carboxylic acids into unusual BCFAs.Key words: Streptomyces avermitilis, fatty acid biosynthesis, avermectin.
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Wendel, Angela A., Daniel E. Cooper, Olga R. Ilkayeva, Deborah M. Muoio e Rosalind A. Coleman. "Glycerol-3-phosphate Acyltransferase (GPAT)-1, but Not GPAT4, Incorporates Newly Synthesized Fatty Acids into Triacylglycerol and Diminishes Fatty Acid Oxidation". Journal of Biological Chemistry 288, n. 38 (1 agosto 2013): 27299–306. http://dx.doi.org/10.1074/jbc.m113.485219.

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Abstract (sommario):
Four glycerol-3-phosphate acyltransferase (GPAT) isoforms, each encoded by a separate gene, catalyze the initial step in glycerolipid synthesis; in liver, the major isoforms are GPAT1 and GPAT4. To determine whether each of these hepatic isoforms performs a unique function in the metabolism of fatty acid, we measured the incorporation of de novo synthesized fatty acid or exogenous fatty acid into complex lipids in primary mouse hepatocytes from control, Gpat1−/−, and Gpat4−/− mice. Although hepatocytes from each genotype incorporated a similar amount of exogenous fatty acid into triacylglycerol (TAG), only control and Gpat4−/− hepatocytes were able to incorporate de novo synthesized fatty acid into TAG. When compared with controls, Gpat1−/− hepatocytes oxidized twice as much exogenous fatty acid. To confirm these findings and to assess hepatic β-oxidation metabolites, we measured acylcarnitines in liver from mice after a 24-h fast and after a 24-h fast followed by 48 h of refeeding with a high sucrose diet to promote lipogenesis. Confirming the in vitro findings, the hepatic content of long-chain acylcarnitine in fasted Gpat1−/− mice was 3-fold higher than in controls. When compared with control and Gpat4−/− mice, after the fasting-refeeding protocol, Gpat1−/− hepatic TAG was depleted, and long-chain acylcarnitine content was 3.5-fold higher. Taken together, these data demonstrate that GPAT1, but not GPAT4, is required to incorporate de novo synthesized fatty acids into TAG and to divert them away from oxidation.
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19

Pech-Canul, Ángel, Joaquina Nogales, Alfonso Miranda-Molina, Laura Álvarez, Otto Geiger, María José Soto e Isabel M. López-Lara. "FadD Is Required for Utilization of Endogenous Fatty Acids Released from Membrane Lipids". Journal of Bacteriology 193, n. 22 (16 settembre 2011): 6295–304. http://dx.doi.org/10.1128/jb.05450-11.

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Abstract (sommario):
FadD is an acyl coenzyme A (CoA) synthetase responsible for the activation of exogenous long-chain fatty acids (LCFA) into acyl-CoAs. Mutation offadDin the symbiotic nitrogen-fixing bacteriumSinorhizobium melilotipromotes swarming motility and leads to defects in nodulation of alfalfa plants. In this study, we found thatS. melilotifadDmutants accumulated a mixture of free fatty acids during the stationary phase of growth. The composition of the free fatty acid pool and the results obtained after specific labeling of esterified fatty acids with a Δ5-desaturase (Δ5-Des) were in agreement with membrane phospholipids being the origin of the released fatty acids.Escherichia colifadDmutants also accumulated free fatty acids released from membrane lipids in the stationary phase. This phenomenon did not occur in a mutant ofE. coliwith a deficient FadL fatty acid transporter, suggesting that the accumulation of fatty acids infadDmutants occurs inside the cell. Our results indicate that, besides the activation of exogenous LCFA, in bacteria FadD plays a major role in the activation of endogenous fatty acids released from membrane lipids. Furthermore, expression analysis performed withS. melilotirevealed that a functional FadD is required for the upregulation of genes involved in fatty acid degradation and suggested that in the wild-type strain, the fatty acids released from membrane lipids are degraded by β-oxidation in the stationary phase of growth.
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20

Yao, Jiangwei, Megan E. Ericson, Matthew W. Frank e Charles O. Rock. "Enoyl-Acyl Carrier Protein Reductase I (FabI) Is Essential for the Intracellular Growth of Listeria monocytogenes". Infection and Immunity 84, n. 12 (10 ottobre 2016): 3597–607. http://dx.doi.org/10.1128/iai.00647-16.

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Abstract (sommario):
Enoyl-acyl carrier protein reductase catalyzes the last step in each elongation cycle of type II bacterial fatty acid synthesis and is a key regulatory protein in bacterial fatty acid synthesis. Genes of the facultative intracellular pathogenListeria monocytogenesencode two functional enoyl-acyl carrier protein isoforms based on their ability to complement the temperature-sensitive growth phenotype ofEscherichia colistrain JP1111 [fabI(Ts)]. The FabI isoform was inactivated by the FabI selective inhibitor AFN-1252, but the FabK isoform was not affected by the drug, as expected. Inhibition of FabI by AFN-1252 decreased endogenous fatty acid synthesis by 80% and lowered the growth rate ofL. monocytogenesin laboratory medium. Robust exogenous fatty acid incorporation was not detected inL. monocytogenesunless the pathway was partially inactivated by AFN-1252 treatment. However, supplementation with exogenous fatty acids did not restore normal growth in the presence of AFN-1252. FabI inactivation prevented the intracellular growth ofL. monocytogenes, showing that neither FabK nor the incorporation of host cellular fatty acids was sufficient to support the intracellular growth ofL. monocytogenes. Our results show that FabI is the primary enoyl-acyl carrier protein reductase of type II bacterial fatty acid synthesis and is essential for the intracellular growth ofL. monocytogenes.
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21

Titov, Vladimir Nicolaevich, e Vladimir Pavlovich Shirinsky. "Insulin resistance: the conflict between biological settings of energy metabolism and human lifestyle (a glance at the problem from evolutionary viewpoint)". Diabetes mellitus 19, n. 4 (31 agosto 2016): 286–94. http://dx.doi.org/10.14341/dm7959.

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Abstract (sommario):
A biological function of the phylogenetically late humoral mediator insulin is to provide energy substrates for locomotion, i.e. movement resulting from contraction of striated muscles. Insulin is able to meet this evolutionary demand of an organism by means of the effective ATP production in the mitochondria. Exogenous fatty acids, optimised endogenous fatty acids produced from glucose and glucose itself are the major substrates for ATP synthesis. Cells stimulated by insulin produce ω-9 С18:1 oleic acid from glucose. This fatty acid is oxidised by the mitochondria at a higher rate than exogenous and endogenous C16:0 palmitic fatty acid. In the normal state of insulin system and mitochondria, the frequent cause of insulin resistance is the non-optimal properties of dietary fatty acids supplied for oxidation by the mitochondria. Dietary excess of saturated palmitic fatty acid over monogenic oleic fatty acid causes insulin resistance to develop. Insulin resistance syndrome is the condition of in vivo energy deficiency and insufficient production of ATP for the realisation of the biological adaptation and compensation. Insulin effectively inhibits lipolysis only in phylogenetically late subcutaneous adipocytes but not in phylogenetically early visceral fat cells of the omentum. Discrepancy in the regulation of energy substrate metabolism against the background of a ‘relative biological perfection’ of higher mammals is the aetiological basis of insulin resistance.
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22

Chattopadhyay, Panchanon, Santu Kumar Banerjee, Kalyani Sen e Parul Chakrabarti. "Lipid profiles of conidia of Aspergillus niger and a fatty acid auxotroph". Canadian Journal of Microbiology 33, n. 12 (1 dicembre 1987): 1116–20. http://dx.doi.org/10.1139/m87-195.

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Abstract (sommario):
Conidial lipids of the wild-type (V35) Aspergillus niger and its unsaturated fatty acid auxotroph (UFA2) were compared. The wild type contained lower levels (7.6%) of phospholipids and higher levels (28.4%) of glycolipids than the mutant (16.5 and 22.2%, respectively). Oleic (33.4%), linoleic (22.5%), palmitic (12.8%), stearic (7.4%), and linolenic (6.2%) were the main fatty acids of the wild type (V35). The mutant grew only in the presence of unsaturated fatty acid having at least one Δ9cis double bond, and its conidial fatty acid profile was influenced by the exogenous acid. Analyses of the fatty acids of UFA2 grown in the presence of different fatty acid supplements support the original view that the mutant is defective in Δ9-desaturase activity.
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23

Liang, Zhenye, Zongzheng Jiang, Sen Wu, Yujia Zhai, Shuqi You e Chang Xu. "Exogenous Fatty Acids Remodel the Muscle Fatty Acids Composition of the GIFT Tilapia (Oreochromis niloticus)". Aquaculture Research 2024 (14 marzo 2024): 1–13. http://dx.doi.org/10.1155/2024/2715178.

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Abstract (sommario):
To reduce the negative impact of fish oil substitutes on the fatty acid composition of farmed fish, this experiment utilized different types of oils as dietary lipid sources for GIFT tilapia. Tilapia oil (FO) was used as the control, along with corn oil (CO), linseed oil (LO), algae oil (AO), and a mixture of linseed oil and algae oil in various ratios of 1 : 2, 1 : 1, and 2 : 1 (LA12, LA11, and LA21) to reshape the fatty acid profile of GIFT tilapia (0.205 ± 0.005 g) in the muscle. The weight gain and specific growth rate of tilapia in the LO and control groups were significantly higher than in other treatments (P<0.05). Meanwhile, despite the AO group exhibited the highest docosahexaenoic acid (DHA) content (P<0.05), it also exhibited the highest levels of malondialdehyde content and superoxide dismutase activity (P<0.05). The mRNA expression levels of Δ6/Δ5 fatty acyl desaturase 2 (Δ6/Δ5FADs2), Δ4 fatty acyl desaturase 2 (Δ4FADs2), acetyl-CoA carboxylase α (ACCα), and elongase of very long chain fatty acids 5 (ELOVL5) in the hepatopancreas of LO group were exhibited a significant upregulation compared to the control (P<0.05). The synthesis of DHA and eicosapentaenoic acid (EPA) in the muscles of LA12, LA11, and LA21 groups increased as the proportion of DHA decreased in the diets. In conclusion, the edible value of fatty acids of tilapia muscle, especially n-3 long-chain polyunsaturated fatty acids, can be significantly improved by adjusting the oil source in the diet through lipid metabolism.
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24

Kingry, Luke C., Jason E. Cummings, Kerry W. Brookman, Gopal R. Bommineni, Peter J. Tonge e Richard A. Slayden. "The Francisella tularensis FabI Enoyl-Acyl Carrier Protein Reductase Gene Is Essential to Bacterial Viability and Is Expressed during Infection". Journal of Bacteriology 195, n. 2 (9 novembre 2012): 351–58. http://dx.doi.org/10.1128/jb.01957-12.

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Abstract (sommario):
ABSTRACTFrancisella tularensisis classified as a category A priority pathogen and causes fatal disseminated disease in humans upon inhalation of less than 50 bacteria. Although drugs are available for treatment, they are not ideal because of toxicity and route of delivery, and in some cases patients relapse upon withdrawal. We have an ongoing program to develop novel FAS-II FabI enoyl-ACP reductase enzyme inhibitors forFrancisellaand other select agents. To establishF. tularensisFabI (FtFabI) as a clinically relevant drug target, we demonstrated that fatty acid biosynthesis and FabI activity are essential for growth even in the presence of exogenous long-chain lipids and that FtfabIis not transcriptionally altered in the presence of exogenous long-chain lipids. Inhibition of FtFabI or fatty acid synthesis results in loss of viability that is not rescued by exogenous long-chain lipid supplementation. Importantly, whole-genome transcriptional profiling ofF. tularensiswith DNA microarrays from infected tissues revealed that FtfabIandde novofatty acid biosynthetic genes are transcriptionally active during infection. This is the first demonstration that the FabI enoyl-ACP-reductase enzyme encoded byF. tularensisis essential and not bypassed by exogenous fatty acids and thatde novofatty acid biosynthetic components encoded inF. tularensisare transcriptionally active during infection in the mouse model of tularemia.
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25

Ravi, Divya, Carmen del Genio, Haider Ghiasuddin e Arti Gaur. "FSMP-15. EVALUATING THE ROLE OF LONG-CHAIN FATTY ACID METABOLISM IN PROMOTING GLIOBLASTOMA GROWTH". Neuro-Oncology Advances 3, Supplement_1 (1 marzo 2021): i19. http://dx.doi.org/10.1093/noajnl/vdab024.079.

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Abstract (sommario):
Abstract Glioblastomas (GBM) or Stage IV gliomas, are the most aggressive of primary brain tumors and are associated with high mortality and morbidity. Patients diagnosed with this lethal cancer have a dismal survival rate of 14 months and a 5-year survival rate of 5.6% despite a multimodal therapeutic approach, including surgery, radiation therapy, and chemotherapy. Aberrant lipid metabolism, particularly abnormally active de novo fatty acid synthesis, is recognized to have a key role in tumor progression and chemoresistance in cancers. Previous studies have reported a high expression of fatty acid synthase (FASN) in patient tumors, leading to multiple investigations of FASN inhibition as a treatment strategy. However, none of these have developed as efficacious therapies. Furthermore, when we profiled FASN expression using The Cancer Genome Atlas (TCGA) we determined that high FASN expression in GBM patients did not confer a worse prognosis (HR: 1.06; p-value: 0.51) and was not overexpressed in GBM tumors compared to normal brain. Therefore, we need to reexamine the role of exogenous fatty acid uptake over de novofatty acid synthesis as a potential mechanism for tumor progression. Our study aims to measure and compare fatty acid oxidation (FAO) of endogenous and exogenous fatty acids between GBM patients and healthy controls. Using TCGA, we have identified the overexpression of multiple enzymes involved in mediating the transfer and activation of long-chain fatty acids (LCFA) in GBM tumors compared to normal brain tissue. We are currently conducting metabolic flux studies to (1) assess the biokinetics of LCFA degradation and (2) establish exogenous versus endogenous LCFA preferences between patient-derived primary GBM cells and healthy glial and immune cells during steady state and glucose-deprivation.
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26

Chamberlin, M. E., e L. J. Mandel. "Substrate support of medullary thick ascending limb oxygen consumption". American Journal of Physiology-Renal Physiology 251, n. 4 (1 ottobre 1986): F758—F763. http://dx.doi.org/10.1152/ajprenal.1986.251.4.f758.

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Abstract (sommario):
The oxygen consumption of medullary thick ascending limb tubule suspensions was measured in the presence and absence of exogenous glucose. In the absence of exogenous glucose, the control oxygen consumption decreased 15%. Under identical conditions, the nystatin-stimulated oxygen consumption was inhibited 36%, indicating that oxidation of endogenous substrates could not meet the ATP demand of the fully stimulated Na+-K+-ATPase. Addition of inhibitors of fatty acid oxidation (bromooctanoate and tetradecylglycidic acid) further inhibited oxygen consumption, revealing that endogenous fats are oxidized in control and nystatin-stimulated states. Inhibition of endogenous carbohydrate (2-deoxy-D-glucose present) or amino acid (aminooxyacetate present) oxidation suppressed the nystatin response. In the presence of 10 mM glucose, only aminooxyacetate inhibited the nystatin-stimulated oxygen consumption, suggesting that the involvement of the malate-aspartate shuttle in redox balance during increased glycolytic flux. Addition of fatty acids or acetoacetate increased the control, nystatin-stimulated and uncoupler-stimulated oxygen consumption of tubules suspended in 10 mM glucose, indicating that these tubules oxidize exogenous fatty acids and ketones and oxidation of exogenous glucose alone may not meet all the energy demands of the tissue. Conversely, the addition of organic acids failed to enhance control oxygen consumption, possibly due to the absence of transport systems for these compounds in the medullary thick ascending limb tubules.(ABSTRACT TRUNCATED AT 250 WORDS)
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27

Zhu, Kun, Xiang Ding, Mudcharee Julotok e Brian J. Wilkinson. "Exogenous Isoleucine and Fatty Acid Shortening Ensure the High Content of Anteiso-C15:0 Fatty Acid Required for Low-Temperature Growth of Listeria monocytogenes". Applied and Environmental Microbiology 71, n. 12 (dicembre 2005): 8002–7. http://dx.doi.org/10.1128/aem.71.12.8002-8007.2005.

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Abstract (sommario):
ABSTRACT Previous studies have demonstrated that the branched-chain fatty acid anteiso-C15:0 plays a critical role in the growth of Listeria monocytogenes at low temperatures by ensuring sufficient membrane fluidity. Studies utilizing a chemically defined minimal medium revealed that the anteiso fatty acid precursor isoleucine largely determined the fatty acid profile and fatty acid response of the organism to lowered growth temperature. When isoleucine was sufficient, the fatty acid profile was very uniform, with anteiso fatty acids comprising up to 95% of total fatty acid, and the major fatty acid adjustment to low temperature was fatty acid chain shortening, which resulted in an increase of anteiso-C15:0 solely at the expense of anteiso-C17:0. When isoleucine was not supplied, the fatty acid profile became more complex and was readily modified by leucine, which resulted in a significant increase of corresponding iso fatty acids and an inability to grow at 10°C. Under this condition, the increase of anteiso-C15:0 at low temperature resulted from the combined effect of increasing the anteiso:iso ratio and chain shortening. A branched-chain α-keto acid dehydrogenase-defective strain largely lost the ability to increase the anteiso:iso ratio. Cerulenin, an inhibitor of β-ketoacyl-acyl carrier protein synthase (FabF), induced a similar fatty acid chain shortening as low temperature did. We propose that the anteiso precursor preferences of enzymes in the branched-chain fatty acid biosynthesis pathway ensure a high production of anteiso fatty acids, and cold-regulated chain shortening results in a further increase of anteiso-C15:0 at the expense of anteiso-C17:0.
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28

Jenkins, Julie K., e Polly D. Courtney. "Lactobacillusgrowth and membrane composition in the presence of linoleic or conjugated linoleic acid". Canadian Journal of Microbiology 49, n. 1 (1 gennaio 2003): 51–57. http://dx.doi.org/10.1139/w03-003.

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Abstract (sommario):
Five Lactobacillus strains of intestinal and food origins were grown in MRS broth or milk containing various concentrations of linoleic acid or conjugated linoleic acid (CLA). The fatty acids had bacteriostatic, bacteriocidal, or no effect depending on bacterial strain, fatty acid concentration, fatty acid type, and growth medium. Both fatty acids displayed dose-dependent inhibition. All strains were inhibited to a greater extent by the fatty acids in broth than in milk. The CLA isomer mixture was less inhibitory than linoleic acid. Lactobacillus reuteri ATCC 55739, a strain capable of isomerizing linoleic acid to CLA, was the most inhibited strain by the presence of linoleic acid in broth or milk. In contrast, a member of the same species, L. reuteri ATCC 23272, was the least inhibited strain by linoleic acid and CLA. All strains increased membrane linoleic acid or CLA levels when grown with exogenous fatty acid. Lactobacillus reuteri ATCC 55739 had substantial CLA in the membrane when the growth medium was supplemented with linoleic acid. No association between level of fatty acid incorporation into the membrane and inhibition by that fatty acid was observed.Key words: Lactobacillus, conjugated linoleic acid, linoleic acid, cell membrane.
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29

Sauro, V. S., e K. P. Strickland. "Changes in oleic acid oxidation and incorporation into lipids of differentiating L6 myoblasts cultured in normal or fatty acid-supplemented growth medium". Biochemical Journal 244, n. 3 (15 giugno 1987): 743–48. http://dx.doi.org/10.1042/bj2440743.

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Abstract (sommario):
L6 myoblasts accumulate large stores of neutral lipid (predominantly triacylglycerol) when cultured in fatty acid-supplemented growth medium. No accumulation of neutral lipid was evident in myotubes (differentiated myoblasts) when treated similarly. Triacylglycerol accumulation was rapid and dependent on exogenous fatty acid concentration. Triacylglycerol content in myoblasts cultured in fatty acid-supplemented growth medium was approx. 3-fold higher than that in myotubes treated similarly and 2-3-fold higher than that in myoblasts cultured in normal growth medium. Incorporation studies using [I-14C]oleic acid showed that myoblasts and myotubes take up exogenous fatty acid at similar rates. However, cells cultured in fatty acid-supplemented growth medium remove more exogenous fatty acid than do cells cultured in normal growth medium. Over 90% of the incorporated label was found in phospholipid and triacylglycerol fractions in all situations studied. Myoblasts incorporated a more significant proportion (P less than 0.001) of label into triacylglycerol compared with that of myotubes. No differences in fatty acid oxidation rates were detected when differentiating L6 cells cultured in normal growth medium were compared with those cultured in fatty acid-supplemented growth medium. However, fatty acid oxidation rates were observed to increase 3-5-fold upon myoblast differentiation. We conclude that there is a marked change in the pattern of lipid metabolism when myoblasts (primarily triacylglycerol-synthesizing cells) differentiate into myotubes (primarily phospholipid-synthesizing cells). Understanding these changes, which coincide with normal muscle development, may be important, since a defect in this natural switch could explain the observed accumulation of lipid in muscle characteristic of some of the muscular dystrophies and other lipid-storage myopathies.
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30

Hopp, J. F., e W. K. Palmer. "Electrical stimulation alters fatty acid metabolism in isolated skeletal muscle". Journal of Applied Physiology 68, n. 6 (1 giugno 1990): 2473–81. http://dx.doi.org/10.1152/jappl.1990.68.6.2473.

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Abstract (sommario):
Little is known about the contribution of plasma free fatty acid (FFA) and intramuscular triacylglycerol (TG) as substrates for energy production during prolonged electrical stimulation of skeletal muscle. The purpose of this study was to investigate the effects of continuous and intermittent electrical stimulation protocols of different intensities on exogenous FFA oxidation, exogenous FFA incorporation into intracellular TG, and intracellular TG content in the isolated in vitro rat flexor digitorum brevis muscle preparation. Muscles were electrically stimulated for 0.5 h continuously at 0.2 Hz or intermittently (30 s on, 60 s off) at 0.2, 0.4, 0.8, and 5.0 Hz while incubated at 37 degrees C in 0.5 mM palmitate-3% bovine serum albumin medium (pH 7.4) in the presence of insulin (100 microU/ml) and glucose (11 mM). Control muscles were frozen immediately after excision or incubated for 0.5 h. At similar frequencies, less exogenous FFA esterification and more exogenous FFA oxidation occurred during continuous than during intermittent stimulation. As the frequency of intermittent stimulation increased, the amount of exogenous FFA esterified decreased and the amount of exogenous FFA oxidized increased. The data also indicate that at least a portion of TG was constantly being hydrolyzed during electrical stimulation. Under stimulation conditions in which exogenous FFA esterification was below the control (resting muscle) level, intramuscular TG content was significantly decreased compared with control TG content values. Thus both plasma FFA and intramuscular TG are substrates for energy production during electrical stimulation. However, the stimulation parameters employed affect the quantities utilized.
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31

WIGGINS, David, e Geoffrey F. GIBBONS. "Origin of hepatic very-low-density lipoprotein triacylglycerol: the contribution of cellular phospholipid". Biochemical Journal 320, n. 2 (1 dicembre 1996): 673–79. http://dx.doi.org/10.1042/bj3200673.

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Abstract (sommario):
When rat hepatocytes were cultured for 24 h in the absence of exogenous fatty acid, the amount of very-low-density lipoprotein (VLDL) triacylglycerol (TAG) secreted (114±14 µg/mg of cell protein) could not be accounted for by the mass of TAG lost from the cells (29±6.1 µg/mg of cell protein) during this period (n = 12). Of the balance (85±14 µg/mg; 94±15 nmol/mg), a maximum of only 37 nmol/mg of cell protein of TAG could be accounted for by fatty acids synthesized de novo. When labelled exogenous oleate (initial concentration, 0.75 mM) was present in the culture medium, the net gain in cellular plus VLDL TAG (253±38 µg/mg of cell protein per 24 h) was greater than that contributed by the exogenous fatty acid (155±18.2 µg/mg of cell protein, n = 5). Again, the balance (98.8±18.2 µg/mg of cell protein per 24 h) was too great to be accounted for by fatty acid synthesis de novo. In experiments in which cellular glycerolipids were prelabelled with [9,10(n)-3H]oleic acid, following removal of the labelled fatty acid, there was a net increase in labelled cellular plus VLDL TAG over the next 24 h. That cellular phospholipids are the source of a substantial part of the excess TAG synthesized is supported by the following evidence. (1) The loss of prelabelled cellular phospholipid during culture was greater than could be accounted for by secretion into the medium. (2) During culture of cells prelabelled with 1,2-di-[1-14C]palmitoyl phosphatidylcholine, a substantial amount of label was secreted as VLDL TAG. (3) In pulse–chase experiments, the kinetics of labelled phospholipid turnover were consistent with conversion into a non-phospholipid pool. The enzymology involved in the transfer of phospholipid fatty acids into TAG is probably complex, but the present results suggest that this pathway may represent an important route by which extracellular fatty acids are channelled into VLDL TAG.
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32

Xu, Tao, Siddharth K. Tripathi, Qin Feng, Michael C. Lorenz, Marsha A. Wright, Melissa R. Jacob, Melanie M. Mask et al. "A Potent Plant-Derived Antifungal Acetylenic Acid Mediates Its Activity by Interfering with Fatty Acid Homeostasis". Antimicrobial Agents and Chemotherapy 56, n. 6 (19 marzo 2012): 2894–907. http://dx.doi.org/10.1128/aac.05663-11.

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Abstract (sommario):
ABSTRACT6-Nonadecynoic acid (6-NDA), a plant-derived acetylenic acid, exhibits strong inhibitory activity against the human fungal pathogensCandida albicans,Aspergillus fumigatus, andTrichophyton mentagrophytes. In the present study, transcriptional profiling coupled with mutant and biochemical analyses were conducted using the model yeastSaccharomyces cerevisiaeto investigate its mechanism of action. 6-NDA elicited a transcriptome response indicative of fatty acid stress, altering the expression of genes that are required for yeast growth in the presence of oleate. Mutants ofS. cerevisiaelacking transcription factors that regulate fatty acid β-oxidation showed increased sensitivity to 6-NDA. Fatty acid profile analysis indicated that 6-NDA inhibited the formation of fatty acids longer than 14 carbons in length. In addition, the growth inhibitory effect of 6-NDA was rescued in the presence of exogenously supplied oleate. To investigate the response of a pathogenic fungal species to 6-NDA, transcriptional profiling and biochemical analyses were also conducted inC. albicans. The transcriptional response and fatty acid profile ofC. albicanswere comparable to those obtained inS. cerevisiae, and the rescue of growth inhibition with exogenous oleate was also observed inC. albicans. In a fluconazole-resistant clinical isolate ofC. albicans, a fungicidal effect was produced when fluconazole was combined with 6-NDA. In hyphal growth assays, 6-NDA inhibited the formation of long hyphal filaments inC. albicans. Collectively, our results indicate that the antifungal activity of 6-NDA is mediated by a disruption in fatty acid homeostasis and that 6-NDA has potential utility in the treatment of superficialCandidainfections.
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33

Liang, Xiaohan, Jianmin Cui, Xuke Yang, Ningbo Xia, Yaqiong Li, Junlong Zhao, Nishith Gupta e Bang Shen. "Acquisition of exogenous fatty acids renders apicoplast-based biosynthesis dispensable in tachyzoites of Toxoplasma". Journal of Biological Chemistry 295, n. 22 (27 aprile 2020): 7743–52. http://dx.doi.org/10.1074/jbc.ra120.013004.

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Abstract (sommario):
Toxoplasma gondii is a common protozoan parasite that infects a wide range of hosts, including livestock and humans. Previous studies have suggested that the type 2 fatty acid synthesis (FAS2) pathway, located in the apicoplast (a nonphotosynthetic plastid relict), is crucial for the parasite's survival. Here we examined the physiological relevance of fatty acid synthesis in T. gondii by focusing on the pyruvate dehydrogenase complex and malonyl-CoA-[acyl carrier protein] transacylase (FabD), which are located in the apicoplast to drive de novo fatty acid biosynthesis. Our results disclosed unexpected metabolic resilience of T. gondii tachyzoites, revealing that they can tolerate CRISPR/Cas9–assisted genetic deletions of three pyruvate dehydrogenase subunits or FabD. All mutants were fully viable in prolonged cultures, albeit with impaired growth and concurrent loss of the apicoplast. Even more surprisingly, these mutants displayed normal virulence in mice, suggesting an expendable role of the FAS2 pathway in vivo. Metabolic labeling of the Δpdh-e1α mutant showed reduced incorporation of glucose-derived carbon into fatty acids with medium chain lengths (C14:0 and C16:0), revealing that FAS2 activity was indeed compromised. Moreover, supplementation of exogenous C14:0 or C16:0 significantly reversed the growth defect in the Δpdh-e1α mutant, indicating salvage of these fatty acids. Together, these results demonstrate that the FAS2 pathway is dispensable during the lytic cycle of Toxoplasma because of its remarkable flexibility in acquiring fatty acids. Our findings question the long-held assumption that targeting this pathway has significant therapeutic potential for managing Toxoplasma infections.
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34

McDonough, Virginia M., e Therese M. Roth. "Growth temperature affects accumulation of exogenous fatty acids and fatty acid composition in Schizosaccharomyces pombe". Antonie van Leeuwenhoek 86, n. 4 (2004): 349–54. http://dx.doi.org/10.1007/s10482-004-0515-0.

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35

McDonough, Virginia M., e Therese M. Roth. "Growth temperature affects accumulation of exogenous fatty acids and fatty acid composition in Schizosaccharomyces pombe". Antonie van Leeuwenhoek 86, n. 4 (gennaio 2005): 349–54. http://dx.doi.org/10.1007/s10482-005-0515-8.

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36

Maghfira, Lativa Lisya, László Stündl, Milán Fehér e Anis Asmediana. "Review on the fatty acid profile and free fatty acid of common carp (Cyprinus carpio)". Acta Agraria Debreceniensis, n. 2 (1 dicembre 2023): 99–105. http://dx.doi.org/10.34101/actaagrar/2/13290.

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Abstract (sommario):
Carp or ponty in Hungarian, is considered commercial freshwater fish, which is an adaptable species in both wild and cultured conditions. Carp has high nutritional value content, favorable taste, it is rich in protein, and low in saturated fat. The nutritional content in fish is composed of many chemical constituents and influenced by many factors. One of the components that its content may be different due to internal and external factors is fatty acids, which may vary depending on endogenous and exogenous factors. The endogenous or internal factors include the genetic, size, sexual maturity, and life cycle phase. While microclimate, water quality, quality of food or diet habit, and the amount of available food or starvation are considered as exogenous or environmental factors. Freshwater fish has the ability to convert essential fatty acid into long chain polyunsaturated fatty acid like AA, EPA, and DHA. Most results showed that palmitic acid and oleic acid were the dominant SFA and MUFA in carp both for wild and farmed carp in all seasons. The PUFA for wild carp was mainly dominated by DHA, while on farmed carp by LA. It confirmed that high LA content in farmed carp was related to the diet habit. The amount of lipid and FA were changed in line with the season. Even the statistical analysis showed no significant difference, but some studies showed a contrasting result. Moreover, most obtained results acknowledged that FA tends to decrease during the spawning period. The amount and composition of FA were affected by the total lipid content. The lipid must be broken down into simpler compounds such as FA or FFA for the metabolism of fish. The result of metabolism then transported into the utilising tissue and used as energy.
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37

Subramanian, Chitra, Charles O. Rock e Yong-Mei Zhang. "DesT Coordinates the Expression of Anaerobic and Aerobic Pathways for Unsaturated Fatty Acid Biosynthesis in Pseudomonas aeruginosa". Journal of Bacteriology 192, n. 1 (30 ottobre 2009): 280–85. http://dx.doi.org/10.1128/jb.00404-09.

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Abstract (sommario):
ABSTRACT The fabA and fabB genes are responsible for anaerobic unsaturated fatty acid formation in Pseudomonas aeruginosa. Expression of the fabAB operon was repressed by exogenous unsaturated fatty acids, and DNA sequences upstream of the translational start site were used to affinity purify DesT. The single protein interaction with the fabAB promoter detected in wild-type cell extracts was absent in the desT deletion strain, as was the repression of fabAB expression by unsaturated fatty acids. Thus, DesT senses the overall composition of the acyl-coenzyme A pool to coordinate the expression of the operons for the anaerobic (fabAB) and aerobic (desCB) pathways for unsaturated fatty acid synthesis.
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38

Kovalevskaya, N. P. "Effect of Auxin on Fatty Acid Composition and Activity of Acyl-Lipid Desaturases in Sprouts of Spring Wheat <i>Triticum aestivum</i> L." Биологические мембраны Журнал мембранной и клеточной биологии 40, n. 1 (1 gennaio 2023): 71–80. http://dx.doi.org/10.31857/s0233475522060081.

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Abstract (sommario):
The effect of exogenous auxin on the fatty acid composition of total lipids in leaves and roots of spring wheat seedlings (Triticum aestivum L.) was studied. It has been established that the diversity of fatty acids in vegetative organs (leaf or root) depends not only on the concentration of auxin, but also on the nitric oxide donor (N2, NO3). It was noted that increasing the concentration of exogenous auxin increased microviscosity and decreased the permeability of the membranes of the vegetative organ in wheat, which was accompanied by a decrease in the double bond index. At the same time, there is an increase in the concentration of saturated fatty acids (palmitic and stearic), which are used as precursors for the formation of fatty acids with a very long chain (VLCFA). It was shown that exogenous auxin leads to an increase in the total content of VLCFAs in leaves with a deficiency (8.4%) and an excess of NO donors (12.3%). The introduction of exogenous auxin eliminates significant differences in the activity of desaturases in wheat roots at different levels of nitric oxide donors. It is suggested that the biosynthesis of docosadienoic acid (C22:2) in leaves is one of the key stages in the formation of an adaptive response of cell membranes to abiotic stresses during plant ontogenesis. An increase in the level of NO promotes the movement of auxin from roots to shoots, which can serve as a regulator of the activity of elongases and desaturases during the synthesis of VLCFAs.
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39

Koundouros, Nikos, e George Poulogiannis. "Reprogramming of fatty acid metabolism in cancer". British Journal of Cancer 122, n. 1 (10 dicembre 2019): 4–22. http://dx.doi.org/10.1038/s41416-019-0650-z.

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Abstract (sommario):
AbstractA common feature of cancer cells is their ability to rewire their metabolism to sustain the production of ATP and macromolecules needed for cell growth, division and survival. In particular, the importance of altered fatty acid metabolism in cancer has received renewed interest as, aside their principal role as structural components of the membrane matrix, they are important secondary messengers, and can also serve as fuel sources for energy production. In this review, we will examine the mechanisms through which cancer cells rewire their fatty acid metabolism with a focus on four main areas of research. (1) The role of de novo synthesis and exogenous uptake in the cellular pool of fatty acids. (2) The mechanisms through which molecular heterogeneity and oncogenic signal transduction pathways, such as PI3K–AKT–mTOR signalling, regulate fatty acid metabolism. (3) The role of fatty acids as essential mediators of cancer progression and metastasis, through remodelling of the tumour microenvironment. (4) Therapeutic strategies and considerations for successfully targeting fatty acid metabolism in cancer. Further research focusing on the complex interplay between oncogenic signalling and dysregulated fatty acid metabolism holds great promise to uncover novel metabolic vulnerabilities and improve the efficacy of targeted therapies.
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40

Forstermann, U., e B. Neufang. "Endothelium-dependent vasodilation by melittin: are lipoxygenase products involved?" American Journal of Physiology-Heart and Circulatory Physiology 249, n. 1 (1 luglio 1985): H14—H19. http://dx.doi.org/10.1152/ajpheart.1985.249.1.h14.

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Abstract (sommario):
Vascular relaxation in response to acetylcholine and other vasodilator compounds has been shown to depend on intact endothelial cells. These dilator compounds obviously induce the formation of an unstable endothelium-derived relaxing factor or factors (EDRF) from the intima which relax the subjacent smooth muscle cells. The chemical identity of this factor (these factors) is still unclear. In the present study we demonstrate that endothelium-dependent relaxation of rabbit aorta was induced by melittin, a polypeptide toxin that activates phospholipase A2 to liberate polyunsaturated fatty acids (especially arachidonic acid) from membrane phospholipids. The relaxation induced by melittin had several properties similar to the acetylcholine relaxation. It was inhibited by potential inhibitors of phospholipase (mepacrine and p-bromophenacylbromide), by inhibitors of lipoxygenase (nordi-hydroguaiaretic acid, compound BW 755C, and 5,8,11,14-eicosatetraynoic acid) but not by the cyclooxygenase inhibitor indomethacin. An exogenous preparation of phospholipase C also induced endothelium-dependent relaxations. These findings support the hypothesis that oxidized metabolites of polyunsaturated fatty acids (e.g., arachidonic acid) may be involved directly (as mediators) or indirectly in the process of endothelium-dependent relaxation. On the other hand, exogenous arachidonic acid was a comparatively weak endothelium-dependent relaxant. However, this does not exclude an important role of endogenous arachidonic acid since the exogenous acid may not sufficiently reach its site of metabolism.
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41

Black, P. N., e Q. Zhang. "Evidence that His110 of the protein FadL in the outer membrane of Escherichia coli is involved in the binding and uptake of long-chain fatty acids: possible role of this residue in carboxylate binding". Biochemical Journal 310, n. 2 (1 settembre 1995): 389–94. http://dx.doi.org/10.1042/bj3100389.

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Abstract (sommario):
The binding of exogenous fatty acids to the outer-membrane protein FadL of Escherichia coli is specific for long-chain fatty acids (C14-C18). Oleoyl alcohol [(Z)-9-octadecen-1-ol] and methyl oleate were unable to displace FadL-specific binding of [3H]oleate (C18:1), suggesting that the carboxylate of the long-chain fatty acid was required for binding. Therefore the binding of exogenous fatty acids to FadL is governed, in part, by the carboxy group of the long-chain fatty acid. Treatment of whole cells with 1 mM diethyl pyrocarbonate (DEPC) depressed binding by 43-73% over the range of oleate concentrations used (10-500 nM). On the basis of these results and the notion that histidine residues often play a role involving proton transfer and charge-pairing, the five histidine residues within FadL (His110, His226, His327, His345 and His418) were replaced by alanine using site-directed mutagenesis. Altered FadL proteins were correctly localized in the outer membrane at wild-type levels and retained the heat-modifiable property characteristic of the wild-type protein. Initial screening of these fadL mutants revealed that the replacement of His110 by Ala resulted in a decreased growth rate on minimal oleate/agar plates. The rates of long-chain fatty acid transport for delta fadL strains harbouring each mutation on a plasmid, with the exception of fadLH110A, were the same, or nearly the same, as those for the wild-type. fadLH110A was also defective in binding, arguing that the functional effect of this mutation was at the level of long-chain-fatty-acid binding.(ABSTRACT TRUNCATED AT 250 WORDS)
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42

Harp, John R., Holly E. Saito, Allen K. Bourdon, Jinnethe Reyes, Cesar A. Arias, Shawn R. Campagna e Elizabeth M. Fozo. "Exogenous Fatty Acids Protect Enterococcus faecalis from Daptomycin-Induced Membrane Stress Independently of the Response Regulator LiaR". Applied and Environmental Microbiology 82, n. 14 (13 maggio 2016): 4410–20. http://dx.doi.org/10.1128/aem.00933-16.

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Abstract (sommario):
ABSTRACTEnterococcus faecalisis a commensal bacterium of the gastrointestinal tract that can cause nosocomial infections in immunocompromised humans. The hallmarks of this organism are its ability to survive in a variety of stressful habitats and, in particular, its ability to withstand membrane damage. One strategy used byE. faecalisto protect itself from membrane-damaging agents, including the antibiotic daptomycin, involves incorporation of exogenous fatty acids from bile or serum into the cell membrane. Additionally, the response regulator LiaR (a member of the LiaFSR [lipid II-interacting antibiotic response regulator and sensor] system associated with cell envelope stress responses) is required for the basal level of resistanceE. faecalishas to daptomycin-induced membrane damage. This study aimed to determine if membrane fatty acid changes could provide protection against membrane stressors in a LiaR-deficient strain ofE. faecalis. We noted that despite the loss of LiaR, the organism readily incorporated exogenous fatty acids into its membrane, and indeed growth in the presence of exogenous fatty acids increased the survival of LiaR-deficient cells when challenged with a variety of membrane stressors, including daptomycin. Combined, our results suggest thatE. faecaliscan utilize both LiaR-dependent and -independent mechanisms to protect itself from membrane damage.IMPORTANCEEnterococcus faecalisis responsible for a significant number of nosocomial infections. Worse, many of the antibiotics used to treatE. faecalisinfection are no longer effective, as this organism has developed resistance to them. The drug daptomycin has been successfully used to treat some of these resistant strains; however, daptomycin-resistant isolates have been identified in hospitals. Many daptomycin-resistant isolates are found to harbor mutations in the genetic locusliaFSR, which is involved in membrane stress responses. Another mechanism shown to increase tolerance to daptomycin involves the incorporation of exogenous fatty acids from host fluids like serum or bile. This improved tolerance was found to be independent ofliaFSRand suggests that there are additional ways to impact sensitivity to daptomycin. Thus, further studies are needed to understand how host fatty acid sources can influence antibiotic susceptibility.
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43

Byers, David M., e Zhiwei Shen. "Biochemical evidence against protein-mediated uptake of myristic acid in the bioluminescent marine bacteriumVibrio harveyi". Canadian Journal of Microbiology 48, n. 10 (1 ottobre 2002): 933–39. http://dx.doi.org/10.1139/w02-092.

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Abstract (sommario):
The bioluminescent marine bacterium, Vibrio harveyi, can utilize exogenous myristic acid (14:0) for β-oxidation, phospholipid and lipid A synthesis, and as an source of myristyl aldehyde for light emission in the V. harveyi dark mutant M17. A variety of genetic and biochemical strategies were employed in an attempt to isolate V. harveyi mutants defective in myristate uptake and to characterize proteins involved in this process. Although [3H]myristate uptake in a tritium suicide experiment decreased the survival of nitrosoguanidine-treated M17 cells by a factor of 105, none of the surviving cells characterized were defective in either incorporation of exogenous myristate into phospholipid or stimulation of light emission. These parameters were also unaffected when intact M17 cells were treated with proteases. Moreover, M17 double mutants selected on the basis of diminished luminescence response to myristate all incorporated [3H]myristate into lipids normally. Finally, no resistant colonies were obtained using the bacteriocidal fatty acid analogue, 11-bromoundecanoate, and experiments with decanoate (10:0) indicated that the V. harveyi cell envelope is very sensitive to physical disruption by fatty acids. Taken together, these results support an unfacilitated uptake of myristic acid in V. harveyi, in contrast with the regulated vectorial transport and activation of long chain fatty acids in Escherichia coli.Key words: Vibrio harveyi, fatty acid transport, bioluminescence, lipid metabolism, tritium suicide.
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44

Malaisse, W. J., F. Malaisse-Lagae, A. Sener e C. Hellerström. "Participation of endogenous fatty acids in the secretory activity of the pancreatic B-cell". Biochemical Journal 227, n. 3 (1 maggio 1985): 995–1002. http://dx.doi.org/10.1042/bj2270995.

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Abstract (sommario):
The pancreatic B-cell may represent a fuel-sensor organ, the release of insulin evoked by nutrient secretagogues being attributable to an increased oxidation of exogenous and/or endogenous substrates. The participation of endogenous fatty acids in the secretory response of isolated rat pancreatic islets was investigated. Methyl palmoxirate (McN-3716, 0.1 mM), an inhibitor of long-chain-fatty-acid oxidation, suppressed the oxidation of exogenous [U-14C]palmitate and inhibited 14CO2 output from islets prelabelled with [U-14C]palmitate. Methyl palmoxirate failed to affect the oxidation of exogenous D-[U-14C]glucose or L-[U-14C]glutamine, the production of NH4+ and the output of 14CO2 from islets prelabelled with L-[U-14C]glutamine. In the absence of exogenous nutrient and after a lag period of about 60 min, methyl palmoxirate decreased O2 uptake to 69% of the control value. Methyl palmoxirate inhibited insulin release evoked by D-glucose, D-glyceraldehyde, 2-oxoisohexanoate, L-leucine, 2-aminobicyclo[2.2.1]heptane-2-carboxylate or 3-phenylpyruvate. However, methyl palmoxirate failed to affect insulin release when the oxidation of endogenous fatty acids was already suppressed, e.g. in the presence of pyruvate or L-glutamine. These findings support the view that insulin release evoked by nutrient secretagogues tightly depends on the overall rate of nutrient oxidation, including that of endogenous fatty acids.
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45

Dorea, J. R. R., e L. E. Armentano. "Effects of common dietary fatty acids on milk yield and concentrations of fat and fatty acids in dairy cattle". Animal Production Science 57, n. 11 (2017): 2224. http://dx.doi.org/10.1071/an17335.

Testo completo
Abstract (sommario):
The objective of the present article was to summarise the effects of five common dietary fatty acids (C16:0, C18:0, C18:1, C18:2 and C18:3) on the major milk fat groups (<C16, C16 and C18). Forty published papers were reviewed to evaluate the effect of adding free fat or oil supplements rich in C16 and C18 fatty acids on the response of milk fat secretion and composition. From those 40 studies, 21 were used to investigate the effect of total dietary concentration of C16:0, C18:0, C18:1, C18:2 and C18:3 on milk secretion or concentrations of milk <C16, C16 and C18 fatty acid groups. The results indicated that C16 supplementation increased total milk fatty acids, mainly by increasing milk C16 yield, without affecting milk <C16 and C18 yield. Supplements rich in unsaturated fatty acid decreased total milk fatty acid by inhibiting secretion of milk fatty acids shorter than C18, with linoleic acid being the most inhibitory. Mixtures of feed fatty acid (C16:0 + C18:0 and C16:0 + C18:1) did not significantly affect total milk fatty acid yield. According to regression of milk C16 yield on dietary fatty acid, endogenous C16 contributes ~80% of total milk C16, but this proportion varies with the level and type of dietary fatty acid fed. Milk mid-infrared analysis can be used to routinely measure the presence of milk <C16 fatty acid, the concentration of which provides a good indicator of inhibition of milk fatty acid secretion. In contrast, measurement of total milk fat content is less effective as a diagnostic tool due to the masking effect of the exogenous supply of C16 and C18 dietary fatty acids.
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46

Wang, Ya-Di, Jiao-Yang Li, Yu Qin, Qiong Liu, Zhe-Zhen Liao e Xin-Hua Xiao. "Exogenous Hydrogen Sulfide Alleviates-Induced Intracellular Inflammation in HepG2 Cells". Experimental and Clinical Endocrinology & Diabetes 128, n. 03 (17 ottobre 2019): 137–43. http://dx.doi.org/10.1055/a-0999-0149.

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Abstract (sommario):
AbstractFatty acids induced hepatic inflammation plays an important role in nonalcoholic fatty liver disease (NAFLD) pathogenesis. Hydrogen sulfide (H2S), an endogenous gasotransmitter, has been established to possess potent anti-inflammation in various human organs. However, the anti-inflammation property of H2S in the fatty liver is still needed to further elucidate. Hence, this study aimed to investigate whether exogenous H2S can protect hepatocytes against inflammation induced by palmitic acid (PA). HepG2 hepatocytes were exposed to PA for 24 h to induce free fatty acids-induced inflammation. The cells were pretreated with NaHS (a donor of H2S) before exposure to PA. Cell viability, inflammatory cytokines (TNF-α, IL-6 and IL-1β), NLRP3 inflammasome and NF-κB were measured by a combination of MTT assay, ELISA, Western blot and Immunofluorescence. Here, we found that exogenous H2S dose-dependently inhibited the expression of pro-inflammatory cytokines, NLRP3 inflammasome and activation of NF-κB signaling in PA-induced HepG2 cells. Thus, H2S might be a candidate therapeutic agent against NAFLD.
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47

Labarthe, François, Maya Khairallah, Bertrand Bouchard, William C. Stanley e Christine Des Rosiers. "Fatty acid oxidation and its impact on response of spontaneously hypertensive rat hearts to an adrenergic stress: benefits of a medium-chain fatty acid". American Journal of Physiology-Heart and Circulatory Physiology 288, n. 3 (marzo 2005): H1425—H1436. http://dx.doi.org/10.1152/ajpheart.00722.2004.

Testo completo
Abstract (sommario):
The spontaneously hypertensive rat (SHR) is a model of cardiomyopathy characterized by a restricted use of exogenous long-chain fatty acid (LCFA) for energy production. The aims of the present study were to document the functional and metabolic response of the SHR heart under conditions of increased energy demand and the effects of a medium-chain fatty acid (MCFA; octanoate) supplementation in this situation. Hearts were perfused ex vivo in a working mode with physiological concentrations of substrates and hormones and subjected to an adrenergic stimulation (epinephrine, 10 μM). 13C-labeled substrates were used to assess substrate selection for energy production. Compared with control Wistar rat hearts, SHR hearts showed an impaired response to the adrenergic stimulation as reflected by 1) a smaller increase in contractility and developed pressure, 2) a faster decline in the aortic flow, and 3) greater cardiac tissue damage (lactate dehydrogenase release: 1,577 ± 118 vs. 825 ± 44 mU/min, P < 0.01). At the metabolic level, SHR hearts presented 1) a reduced exogenous LCFA contribution to the citric acid cycle flux (16 ± 1 vs. 44 ± 4%, P < 0.001) and an enhanced contribution of endogenous substrates (20 ± 4 vs. 1 ± 4%, P < 0.01); and 2) an increased lactate production from glycolysis, with a greater lactate-to-pyruvate production ratio. Addition of 0.2 mM octanoate reduced lactate dehydrogenase release (1,145 ± 155 vs. 1,890 ± 89 mU/min, P < 0.001) and increased exogenous fatty acid contribution to energy metabolism (23.7 ± 1.3 vs. 15.8 ± 0.8%, P < 0.01), which was accompanied by an equivalent decrease in unlabeled endogenous substrate contribution, possibly triglycerides (11.6 ± 1.5 vs. 19.0 ± 1.2%, P < 0.01). Taken altogether, these results demonstrate that the SHR heart shows an impaired capacity to withstand an acute adrenergic stress, which can be improved by increasing the contribution of exogenous fatty acid oxidation to energy production by MCFA supplementation.
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48

Probst, I., R. Spahr, C. Schweickhardt, D. H. Hunneman e H. M. Piper. "Carbohydrate and fatty acid metabolism of cultured adult cardiac myocytes". American Journal of Physiology-Heart and Circulatory Physiology 250, n. 5 (1 maggio 1986): H853—H860. http://dx.doi.org/10.1152/ajpheart.1986.250.5.h853.

Testo completo
Abstract (sommario):
The energy metabolism of exogenous and endogenous substrates was investigated in Ca-tolerant adult ventricular myocytes in short-term culture. CO2 production from exogenous glucose (5 mM), lactate (5 mM), and palmitate (100 microM) were 8, 20, and 29 mumol X h-1 X g wet wt-1. Endogenous lipolysis shared in energy production by 78, 61, and 31%, respectively. Fatty acids represented the main respiratory fuel even when 10(-7) M insulin, 5 mM lactate, or 5 mM dichloroacetate were supplied in addition to glucose. With palmitate, triglyceride contents were doubled within 3 h of cell incubation. With 5 mM glucose as sole exogenous substrate the energy turnover in these resting cells resembled that of arrested hearts, corresponding to 2 ml O2 X min-1 X 100 g wet wt-1. It is concluded that the basic features of substrate metabolism resemble those of the intact myocardium in that fatty acids represent the major fuel, but the contribution of endogenous lipolysis is greater than in the beating heart.
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49

Martínez-Micaelo, N., N. González-Abuín, M. Pinent, A. Ardévol e M. Blay. "Dietary fatty acid composition is sensed by the NLRP3 inflammasome: omega-3 fatty acid (DHA) prevents NLRP3 activation in human macrophages". Food & Function 7, n. 8 (2016): 3480–87. http://dx.doi.org/10.1039/c6fo00477f.

Testo completo
Abstract (sommario):
The NLRP3 inflammasome is considered to be a pivotal host platform responsible for sensing of exogenous and endogenous danger signals, including those generated as a result of metabolic dysregulation, and for the subsequent, IL-1β-mediated orchestration of inflammatory response.
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50

Chatham, John C., Zhi-Ping Gao e John R. Forder. "Impact of 1 wk of diabetes on the regulation of myocardial carbohydrate and fatty acid oxidation". American Journal of Physiology-Endocrinology and Metabolism 277, n. 2 (1 agosto 1999): E342—E351. http://dx.doi.org/10.1152/ajpendo.1999.277.2.e342.

Testo completo
Abstract (sommario):
The aim of this study was to investigate the effect of increasing exogenous palmitate concentration on carbohydrate and palmitate oxidation in hearts from control and 1-wk diabetic rats. Hearts were perfused with glucose, [3-13C]lactate, and [U-13C]palmitate. Substrate oxidation rates were determined by combining13C-NMR glutamate isotopomer analysis of tissue extracts with measurements of oxygen consumption. Carbohydrate oxidation was markedly depressed after diabetes in the presence of low (0.1 mM) but not high (1.0 mM) palmitate concentration. Increasing exogenous palmitate concentration 10-fold resulted in a 7-fold increase in the contribution of palmitate to energy production in controls but only a 30% increase in the diabetic group. Consequently, at 0.1 mM palmitate, the rate of fatty acid oxidation was higher in the diabetic group than in controls; however, at 1.0 mM fatty acid oxidation, it was significantly depressed. Therefore, after 1 wk of diabetes, the major differences in carbohydrate and fatty acid metabolism occur primarily at low rather than high exogenous palmitate concentration.
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