scholarly journals Factors regulating the secretion of lysophosphatidylcholine by rat hepatocytes compared with the synthesis and secretion of phosphatidylcholine and triacylglycerol. Effects of albumin, cycloheximide, verapamil, EGTA and chlorpromazine

1988 ◽  
Vol 253 (3) ◽  
pp. 687-692 ◽  
Author(s):  
A Graham ◽  
A J Bennett ◽  
A A M McLean ◽  
V A Zammit ◽  
D N Brindley
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Rat Hepatocytes ◽  
Absolute Concentration ◽  
Monolayer Cultures ◽  
The Absolute

1. The synthesis and secretion of glycerolipid by monolayer cultures of rat hepatocytes was measured by determining the incorporations of [3H]glycerol, [3H]oleate and [14C]choline and by the absolute concentration of triacylglycerol. 2. The presence of albumin in the medium stimulated the accumulation of lysophosphatidylcholine in the medium by 11-13-fold. 3. Cycloheximide did not significantly alter the accumulation of lysophosphatidylcholine. 4. This process was particularly sensitive to inhibition by chlorpromazine and verapamil, compared with the secretion of triacylglycerol and phosphatidylcholine. By contrast, it was relatively less sensitive to EGTA. 5. It is suggested that intracellular Ca2+ may be important in the production of lysophosphatidylcholine, which then accumulates in the medium by binding to albumin. In vivo this lysophosphatidycholine may be a means of delivering choline and polyunsaturated fatty acids to other organs.

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 Polyunsaturated ω-3 fatty acids inhibit ACE2-controlled SARS-CoV-2 binding and cellular entry

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Goc ◽  
Aleksandra Niedzwiecki ◽  
Matthias Rath
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Eicosapentaenoic Acid ◽  
Linolenic Acid ◽  
Cathepsin L ◽  
Saturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
In Vivo Experiments ◽  
Lipid Compounds

AbstractThe strain SARS-CoV-2, newly emerged in late 2019, has been identified as the cause of COVID-19 and the pandemic declared by WHO in early 2020. Although lipids have been shown to possess antiviral efficacy, little is currently known about lipid compounds with anti-SARS-CoV-2 binding and entry properties. To address this issue, we screened, overall, 17 polyunsaturated fatty acids, monounsaturated fatty acids and saturated fatty acids, as wells as lipid-soluble vitamins. In performing target-based ligand screening utilizing the RBD-SARS-CoV-2 sequence, we observed that polyunsaturated fatty acids most effectively interfere with binding to hACE2, the receptor for SARS-CoV-2. Using a spike protein pseudo-virus, we also found that linolenic acid and eicosapentaenoic acid significantly block the entry of SARS-CoV-2. In addition, eicosapentaenoic acid showed higher efficacy than linolenic acid in reducing activity of TMPRSS2 and cathepsin L proteases, but neither of the fatty acids affected their expression at the protein level. Also, neither reduction of hACE2 activity nor binding to the hACE2 receptor upon treatment with these two fatty acids was observed. Although further in vivo experiments are warranted to validate the current findings, our study provides a new insight into the role of lipids as antiviral compounds against the SARS-CoV-2 strain.

Total Synthesis of DHA and DPAn-3 non-enzymatic oxylipins

Synthesis ◽  
2021 ◽  
Author(s):  
alexandre guy ◽  
Jérémy Merad ◽  
Thomas Degrange ◽  
Guillaume Reversat ◽  
Valérie Bultel-Poncé ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Docosahexaenoic Acid ◽  
Polyunsaturated Fatty Acids ◽  
Total Synthesis ◽  
Biological Properties ◽  
Chemical Structures ◽  
Structural Variety ◽  
Synthetic Strategy

Oxylipins are formed in-vivo from polyunsaturated fatty acids (PUFAs). A large structural variety of compounds is grouped under the term oxylipins, which differ from their formation mechanism (involving enzymes or not), as well as their chemical structures (cyclopentanes, tetrahydrofurans, hydroxylated-PUFA etc.). All structures of oxylipins are of great biological interests. Directly correlated to oxidative stress phenomenon, non-enzymatic oxylipins are used as systemic and/or specific biomarkers in various pathologies and more especially, they were found to have their own biological properties. Produced in-vivo as a non-separable mixture of isomers, total synthesis is a keystone to answer biological questions. In this work, we described the total synthesis of three non-enzymatic oxylipins derived from docosahexaenoic acid (DHA) and docosapentanoic acid (DPAn-3) using a unique and convergent synthetic strategy.

scholarly journals Fatty acids reverse the cyclic AMP inhibition of triacylglycerol and phosphatidylcholine synthesis in rat hepatocytes

1983 ◽  
Vol 216 (1) ◽  
pp. 129-136 ◽  
Author(s):  
S L Pelech ◽  
P H Pritchard ◽  
D N Brindley ◽  
D E Vance
Keyword(s):  
Fatty Acids ◽  
Cyclic Amp ◽  
Rat Hepatocytes ◽  
Phosphocholine Cytidylyltransferase ◽  
Triacylglycerol Synthesis ◽  
Monolayer Cultures ◽  
Membrane Bound ◽  
Amp Inhibition ◽  
Phosphatidylcholine Synthesis

The influence of cyclic AMP analogues and fatty acids on glycerolipid biosynthesis in monolayer cultures of rat hepatocytes was investigated. Chlorophenylthio-cyclic AMP and adenosine 3′:5′-cyclic phosphorothioate inhibited the rate of triacylglycerol synthesis from [1(3)-3H]glycerol, and phosphatidylcholine synthesis from [Me-3H]-choline. Supplementation of the hepatocytes with palmitate (1 mM) reversed chlorophenylthio-cyclic AMP inhibition of triacylglycerol synthesis. Similarly, cyclic AMP analogue-inhibition of phosphatidylcholine synthesis was abolished when the cells were simultaneously incubated with oleate (3 mM). Reactivation of phosphatidylcholine synthesis in chlorophenylthio-cyclic AMP-supplemented cells with oleate was accompanied by conversion of CTP: phosphocholine cytidylyltransferase into the membrane-bound form, since these cells released the enzyme more slowly after treatment with digitonin. The opposing actions of cyclic AMP and fatty acids are discussed in relation to the regulation of glycerolipid biosynthesis during starvation, diabetes and stress.

Effect of thyroid hormones on angiotensinogen production in the rat in vivo and in vitro

1987 ◽  
Vol 115 (2) ◽  
pp. 311-315 ◽  
Author(s):  
M. Ruiz ◽  
M. Montiel ◽  
E. Jimenez ◽  
M. Morell
Keyword(s):  
Thyroid Hormones ◽  
Time Course ◽  
Plasma Renin ◽  
Rat Hepatocytes ◽  
In Vitro System ◽  
Adult Rat ◽  
Monolayer Cultures ◽  
Thyroid Dysfunctions

ABSTRACT The influence of thyroid hormones on angiotensinogen production was studied in vitro and in vivo. In the in-vitro system, angiotensinogen production rate (APR) of monolayer cultures of rat hepatocytes in response to tri-iodothyronine (T3) and thyroxine (T4) was assayed. In the in-vivo system, plasma angiotensinogen concentration (PAC) and liver angiotensinogen content (LAC) were measured in hyper- and hypothyroid rats. In both thyroid dysfunctions, a significant decrease of PAC was found compared with that in control animals; however, LAC showed a significant increase in hyperthyroidism and a marked decrease in hypothyroidism. As PAC is dependent upon both angiotensinogen production by the liver and angiotensinogen degradation by renin, the decrease in PAC observed in hyperthyroidism could be due to an increase in plasma renin concentration, which would overcome the increased synthesis of liver angiotensinogen observed in these animals. In fact, addition of various concentrations of T4 or T3 to monolayer cultures of adult rat hepatocytes significantly enhanced APR. This increase was greater and started earlier with T3 (1196·1 ± 143·7 (s.d.) pg/mg protein per 6-h incubation; significant differences at the third hour of incubation) than with T4 (858·3 ± 88·2 pg/mg protein per 6-h incubation; significant differences at the sixth hour of incubation). In addition, a close dose–response relationship was found in the cultures supplemented with T3. The different time-course in the response elicited by T3 and T4 on APR could be a consequence of the necessary transformation of T4 into T3 to acquire biological activity. J. Endocr. (1987) 115, 311–315

scholarly journals n-3 polyunsaturated fatty acids abrogate mTORC1/2 signaling and inhibit adrenocortical carcinoma growth in vitro and in vivo

2016 ◽  
Vol 35 (6) ◽  
pp. 3514-3522 ◽  
Author(s):  
JUN LIU ◽  
MEINIAN XU ◽  
YONGBIN ZHAO ◽  
CHUNPING AO ◽  
YUKUN WU ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Adrenocortical Carcinoma
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