scholarly journals Polyunsaturated fatty acids inhibit fatty acid synthase and spot-14-protein gene expression in cultured rat hepatocytes by a peroxidative mechanism

1999 ◽  
Vol 341 (2) ◽  
pp. 371-376 ◽  
Author(s):  
Marc FORETZ ◽  
Fabienne FOUFELLE ◽  
Pascal FERRÉ
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Lactate Dehydrogenase ◽  
Polyunsaturated Fatty Acids ◽  
Fatty Acid Synthase ◽  
Rat Hepatocytes ◽  
Inhibitory Effect ◽  
Spot 14

In vivo, polyunsaturated fatty acids (PUFA) inhibit the expression of hepatic genes related to the lipogenic process such as fatty acid synthase and spot-14-protein (S14) genes. In vitro studies have suggested that this was a direct transcriptional effect of PUFA. In hepatocytes, the inhibition of the lipogenic rate by PUFA is not specific, but is linked to a cytotoxic effect due to peroxidative mechanisms. We have investigated whether peroxidation could also explain the inhibitory effect of PUFA on gene expression. Rat hepatocytes were cultured for 24 h with mono-unsaturated or PUFA. PUFA inhibited the expression of fatty acid synthase and S14 genes, and this inhibition was directly related to the number of unsaturations. However, the β-actin and albumin mRNA concentrations were also affected by the most unsaturated fatty acids, suggesting a non-specific effect of PUFA on gene expression. Measurement of lactate dehydrogenase released into the medium indicated a cytotoxicity of PUFA. This was associated with their peroxidation as evaluated by the presence of thiobarbituric acid-reactive substances in the culture medium. The addition of high concentrations of antioxidants abolished lipid peroxidation and lactate dehydrogenase leakage and completely reversed the inhibitory effect of PUFA on gene expression. This suggests (i) that the results obtained previously in cultured hepatocytes in the presence of low concentrations of antioxidants must be interpretated cautiously and (ii) that in vivo, the inhibitory effect of PUFA on lipogenesis-related genes could be indirect through hormonal or metabolic changes or that their effect on gene expression is somehow linked to peroxidative mechanisms.

scholarly journals Fatty Acid Synthesis Is Essential for Survival of Cryptococcus neoformans and a Potential Fungicidal Target

2007 ◽  
Vol 51 (10) ◽  
pp. 3537-3545 ◽  
Author(s):  
Methee Chayakulkeeree ◽  
Thomas H. Rude ◽  
Dena L. Toffaletti ◽  
John R. Perfect
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cryptococcus Neoformans ◽  
Fatty Acid Synthase ◽  
Acid Synthesis ◽  
Yeast Cells ◽  
Synthase Inhibitor ◽  
The Brain

ABSTRACT Fatty acid synthase in the yeast Cryptococcus neoformans is composed of two subunits encoded by FAS1 and FAS2 genes. We inserted a copper-regulated promoter (P CTR4-2 ) to regulate FAS1 and FAS2 expression in Cryptococcus neoformans (strains P CTR4-2 /FAS1 and P CTR4-2 /FAS2, respectively). Both mutants showed growth rates similar to those of the wild type in a low-copper medium in which FAS1 and FAS2 were expressed, but even in the presence of exogenous fatty acids, strains were suppressed in growth under high-copper conditions. The treatment of C. neoformans with fluconazole was shown to have an increased inhibitory activity and even became fungicidal when either FAS1 or FAS2 expression was suppressed. Furthermore, a subinhibitory dose of fluconazole showed anticryptococcal activity in vitro in the presence of cerulenin, a fatty acid synthase inhibitor. In a murine model of pulmonary cryptococcosis, a tissue census of yeast cells in P CTR4-2 /FAS2 strain at day 7 of infection was significantly lower than that in mice treated with tetrathiomolybdate, a copper chelator (P < 0.05), and a yeast census of P CTR4-2 /FAS1 strain at day 14 of infection in the brain was lower in the presence of more copper. In fact, no positive cultures from the brain were detected in mice (with or without tetrathiomolybdate treatment) infected with the P CTR4-2 /FAS2 strain, which implies that this mutant did not reach the brain in mice. We conclude that both FAS1 and FAS2 in C. neoformans are essential for in vitro and in vivo growth in conditions with and without exogenous fatty acids and that FAS1 and FAS2 can potentially be fungicidal targets for C. neoformans with a potential for synergistic behavior with azoles.

scholarly journals Induction of Fatty-Acid-Synthase Gene Expression by Glucose in Primary Culture of Rat Hepatocytes. Dependency upon Glucokinase Activity

1995 ◽  
Vol 230 (1) ◽  
pp. 309-315 ◽  
Author(s):  
Carina Prip-Buus ◽  
Dominique Perdereau ◽  
Fabienne Foufelle ◽  
Jocelyne Maury ◽  
Pascal Ferre ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Primary Culture ◽  
Fatty Acid Synthase ◽  
Rat Hepatocytes ◽  
Fatty Acid Synthase Gene

scholarly journals A tissue-specific increase in lipogenesis in rat brown adipose tissue in hypothyroidism

1988 ◽  
Vol 251 (2) ◽  
pp. 553-557 ◽  
Author(s):  
H S Baht ◽  
E D Saggerson
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Maximum Activity ◽  
Brown Adipocyte ◽  
Glycolytic Flux ◽  
Brown Adipocytes ◽  
White Adipocytes ◽  
Brown Adipose

1. Rats were made hypothyroid by feeding them with propylthiouracil together with a low-iodine diet for 4 weeks. 2. [U-14C]Glucose conversion into fatty acids was substantially enhanced in brown adipocytes isolated from hypothyroid rats. Incorporation of 3H2O into fatty acids in vivo was enhanced in hypothyroidism in interscapular brown fat, but not in epididymal white fat or in liver. Hypothyroidism increased the activities of fatty acid synthase and ATP citrate lyase in brown, but not in white, adipocytes. 3. Glycolytic flux in brown adipocytes, quantified by [3-3H]glucose detritiation, was increased by hypothyroidism. This change was accompanied by increased maximum activity of phosphofructokinase. In white adipocytes a large increase in phosphofructokinase maximum activity was observed in hypothyroidism, but this change was accompanied by only small increases in the rate of glucose detritiation by incubated cells. It is suggested that in the brown adipocyte the overall conversion of glucose into fatty acids is enhanced in thyroid deficiency, but that this change is muted in the white adipocyte, possibly because of limitation of glucose transport. 4. Fatty acid synthesis in brown adipocytes from hypothyroid animals was considerably less sensitive to inhibition by exogenous fatty acids than is the process in cells from euthyroid animals. Consequently, the effect of hypothyroidism to enhance lipogenesis is amplified in the presence of physiological concentrations of fatty acid.

scholarly journals Dietary Coleus Amboinicus Herb Decreases Ruminal Methanogenesis and Biohydrogenation, and Improves Meat Quality and Fatty Acid Composition in Longissimus Thoracis of Lambs

2021 ◽  
Author(s):  
Yulianri Rizki Yanza ◽  
Malgorzata Szumacher-Strabel ◽  
Dorota Lechniak ◽  
Sylwester Ślusarczyk ◽  
Pawel Kolodziejski ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Meat Quality ◽  
Methane Production ◽  
Fatty Acid Synthase ◽  
Unsaturated Fatty Acids ◽  
Biologically Active ◽  
Coleus Amboinicus

Abstract Background: This study aimed to investigate the effect of biologically active compounds (BAC) of Coleus amboinicus Lour. (CAL) herb fed to growing lambs on ruminal methane production, ruminal biohydrogenation of unsaturated fatty acids and meat characteristics. An in vitro trial (Experiment 1) comprising of control and three experimental diets (CAL constituting 10%, 15%, and 20% of the total diet) was conducted to determine an effective dose for in vivo experiments. After the in vitro trial, two in vivo experiments were conducted on six growing, rumen-cannulated lambs (Experiment 2) and 16 growing lambs (Experiment 3), which were assigned into the control (CON) and one experimental diet (20% of CAL). Several parameters were examined in vitro (pH, ammonia and VFA concentrations, protozoa, methanogens and select bacteria populations) and in vivo (methane production, digestibility, ruminal microorganism populations, meat quality, fatty acids profiles in rumen fluid and meat, transcript expression of 5 genes in meat). Results: The CAL lowered in vitro methane production by 51%. In the in vivo experiments, lambs fed CAL decreased methane production by 20% compared with the CON animals (Experiment 3), which corresponded to the reduced total methanogens counts in all experiments up to 28%, notably Methanobacteriales. In Experiment 3, CAL increased or tended to increase the numbers of Ruminococcus albus, Megasphaeraelsdenii, Butyrivibrioproteoclasticus, and Butyrivibriofibrisolvens. Dietary CAL suppressed the Holotricha population, but increased or tended to increase Entodiniomorpha population in Experiments 2 and 3. An increase in the polyunsaturated fatty acid (PUFA) proportion in the rumen of lambs was noted in response to the CAL diet, which was mainly attributable to the increase in C18:3 cis-9 cis-12 cis-15 (LNA) proportion. The CAL reduced the mRNA expressions of four investigated genes in meat (fatty acid synthase, stearoyl-CoA desaturase, lipoprotein lipase, and fatty acid desaturase 1). Conclusions:Summarizing, polyphenols of CAL (20% in diet) origin can mitigate ruminal methane production by inhibiting the methanogens communities. Supplementation of CAL also provides favorable conditions in the rumen by modulating ruminal bacteria involved in fermentation and biohydrogenation of fatty acids. CAL elevated the LNA concentration, which led to improved meat quality through increased deposition of n-3 PUFA.

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