scholarly journals Effects of vasopressin and corticosterone on fatty acid metabolism and on the activities of glycerol phosphate acyltransferase and phosphatidate phosphohydrolase in rat hepatocytes

1984 ◽  
Vol 217 (2) ◽  
pp. 461-469 ◽  
Author(s):  
A D Pollard ◽  
D N Brindley
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Rat Hepatocytes ◽  
Ionophore A23187 ◽  
Brattleboro Rats ◽  
Glycerol Phosphate ◽  
Isolated Rat Hepatocytes ◽  
Triacylglycerol Synthesis ◽  
Phosphatidate Phosphohydrolase

The effects of vasopressin on the short-term control of fatty acid metabolism were studied in isolated rat hepatocytes. Vasopressin increased the oxidation of oleate to CO2 and decreased the formation of ketones in hepatocytes from Wistar rats, but not from Brattleboro rats. Incubation with vasopressin for 30 min increased the conversion of oleate into triacylglycerol by 17% and 32% in hepatocytes from Wistar and Brattleboro rats respectively. The corresponding increases for the phospholipid fraction were 19% and 42%. When Wistar-rat hepatocytes were incubated with corticosterone for 6 h there was a 19% increase in triacylglycerol synthesis, and a 52% increase if vasopressin was added 30 min before the end of the incubation. Glycerol phosphate acyltransferase activity was not significantly increased by vasopressin. Incubation for 5-60 min with vasopressin increased the Vmax. of phosphatidate phosphohydrolase by 48% and 32% respectively in hepatocytes from Wistar and Brattleboro rats. These increases were antagonized if EGTA was added to the medium used for incubating the hepatocytes. The replacement of vasopressin by 5 microM-ionophore A23187 produced a significant increase of 13% in the phosphohydrolase activity. It is therefore likely that the effects of vasopressin on the phosphohydrolase are mediated by Ca2+. These results are discussed in relation to the possible function of phosphatidate phosphohydrolase in controlling the turnover of phosphoinositides, the synthesis of phosphatidylethanolamine, phosphatidylcholine and triacylglycerol, and the secretion of very-low-density lipoproteins.

scholarly journals Valproic Acid Inhibits Leptin Secretion and Reduces Leptin Messenger Ribonucleic Acid Levels in Adipocytes

Endocrinology ◽  
2004 ◽  
Vol 145 (12) ◽  
pp. 5493-5503 ◽  
Author(s):  
Diane C. Lagace ◽  
Roger S. McLeod ◽  
Mark W. Nachtigal
Keyword(s):  
Valproic Acid ◽  
Fatty Acid ◽  
Weight Gain ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Binding Protein ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Messenger Ribonucleic Acid ◽  
Triacylglycerol Synthesis

Abstract Treatment of epilepsy or bipolar disorder with valproic acid (VPA) induces weight gain and increased serum levels for the satiety hormone, leptin, through an unidentified mechanism. In this study we tested the effects of VPA, a short-chain branched fatty acid (C8:0), on leptin biology and fatty acid metabolism in 3T3-L1 adipocytes. VPA significantly reduced leptin secretion in a dose-dependent manner. Because fatty acid accumulation has been hypothesized to block leptin secretion, we tested the effect of VPA on fatty acid metabolism. Using 14C-radiolabeled VPA, we found that the 14C was mainly incorporated into triacylglycerol. VPA did not alter lipogenesis from acetate, nor did it change the amount of intracellular free fatty acids available for triacylglycerol synthesis. Decreased leptin secretion was accompanied by a reduction in leptin mRNA, even though VPA treatment did not alter the protein levels for known transcription factors affecting leptin transcription including: CCAAT/enhancer binding protein-α, peroxisome proliferator-activated receptor-γ, or steroid regulatory element binding protein 1a. VPA altered levels of leptin mRNA independent of de novo protein synthesis without affecting leptin mRNA degradation. This report demonstrates that VPA decreases leptin secretion and mRNA levels in adipocytes in vitro, suggesting that VPA therapy may be associated with altered leptin homeostasis contributing to weight gain in vivo.

scholarly journals Fatty acid metabolism in hepatocytes cultured with hypolipidaemic drugs. Role of carnitine

1988 ◽  
Vol 253 (1) ◽  
pp. 161-167 ◽  
Author(s):  
P Gerondaes ◽  
K G M M Alberti ◽  
L Agius
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Rat Hepatocytes ◽  
Beta Oxidation ◽  
Carnitine Acyltransferase ◽  
Periportal Zone ◽  
Palmitate Metabolism

The direct effects of clofibrate analogues on carnitine acyltransferase activities and fatty acid metabolism were studied in cultured hepatocytes. Rat hepatocytes cultured with bezafibrate or ciprofibrate (0.1-10 micrograms/ml) for 48 h had increased activities of carnitine acetyltransferase (CAT; 4-6-fold) and carnitine palmitoyltransferase (CPT; 12-34%). The increase in CAT was higher in hepatocytes from the periportal zone (440%) of rat liver compared with cells from the perivenous zone (266%). In human hepatocytes, in contrast with rat, the fibrates did not cause a marked increase in CAT activity. The effects of fibrates on palmitate metabolism were dependent on the carnitine status. In the presence of exogenous carnitine (1 mM), rat hepatocytes cultured with bezafibrate had higher rates of total palmitate metabolism (29-34%) without increased partitioning of palmitate towards beta-oxidation, relative to control cultures. At low endogenous carnitine concentrations, cells cultured with bezafibrate had a greater increase in palmitate metabolism, esterification and cellular accumulation of triacylglycerol compared with the corresponding increases in the presence of carnitine. The changes in palmitate metabolism at either high or low carnitine concentrations were small in comparison with the changes in CAT activity. It is concluded that the increase in hepatic carnitine that occurs in vivo after fibrate feeding probably plays the major role in the changes in partitioning of fatty acid between beta-oxidation and esterification.

scholarly journals Metabolic effects of bacitracin in isolated rat hepatocytes

1983 ◽  
Vol 216 (2) ◽  
pp. 369-375 ◽  
Author(s):  
L Agius ◽  
C Wilding ◽  
K G M M Alberti
Keyword(s):  
Fatty Acid ◽  
Pyruvate Dehydrogenase ◽  
Acid Metabolism ◽  
Tricarboxylic Acid Cycle ◽  
Rat Hepatocytes ◽  
Pyruvate Dehydrogenase Kinase ◽  
Metabolic Effects ◽  
Acid Oxidation ◽  
Isolated Rat Hepatocytes ◽  
Intracellular Processing

Bacitracin is a proteolytic inhibitor which interacts with the intracellular processing of insulin. Its effects on pyruvate, fatty acid and amino acid metabolism were examined in rat hepatocyte suspensions. Bacitracin (0.25-1.0 mM) increased the oxidation of [1-14C]pyruvate by 50-70% and presumably therefore increased the flux through pyruvate dehydrogenase. This was found both in the presence of extracellular Ca2+ and in its absence, but not in the presence of 2 mM-2-chloropropionate, which inhibits pyruvate dehydrogenase kinase. Insulin did not further stimulate [1-14C]pyruvate oxidation in the presence of 1 mM-bacitracin. Bacitracin decreased 14CO2 formation from [2-14C]pyruvate (20-40%) and [U-14C]palmitate (30-70%), suggesting a decreased flux through the tricarboxylic acid cycle. Fatty acid oxidation before acetyl-CoA formation was also decreased. Bacitracin decreased the incorporation of label from [3H]leucine into protein in the absence of insulin, but not in its presence. Bacitracin is commonly used in studies on insulin action. Our results suggest that in such studies the effects noted may be related not only to an interaction of bacitracin with the intracellular processing of insulin but also to direct metabolic effects of bacitracin independent of insulin.

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