Influence of Dietary Fatty Acids on Liver and Adipose Tissue Lipogenesis and on Liver Metabolites in Meal-Fed Rats

Abstract

Rats were trained to eat a fat-free high carbohydrate diet from 800 to 1100 hours each day. After adaptation to meal-eating, the fat-free diet was supplemented with 8% methyl stearate (C_18:0) or 3% methyl linoleate (C_18:2) for 7 days. Relative to the fat-free group, hepatic utilization of acetate unit equivalents (C₂ units) for fatty acid synthesis per mg soluble protein by the C_18:0 group was not significantly altered, whereas C_18:2 supplementation significantly depressed hepatic fatty acid synthesis. Supplemental C_18:2 also caused a significant decline in liver fatty acid synthetase and acetyl CoA carboxylase while fat-free and C_18:0 groups displayed similar enzyme activities. Within a treatment, C₂ unit utilization for in vivo fatty acid synthesis was identical to that of acetyl CoA carboxylase and fatty acid synthetase activities in vitro. Therefore, shortly after a meal, the hepatic activities of these two enzymes appear to be functioning at near capacity. C_18:2 supplementation to the fat-free diet for 7 days caused a 25% decline in glucokinase and pyruvate kinase activities, but only pyruvate kinase was significantly depressed. In contrast, citrate cleavage enzyme and fatty acid synthetase were both significantly reduced in activity by 50%. Plasma unesterified fatty acid levels in rats fed C_18:2 for 5 days were not significantly elevated prior to a meal, although dietary C_18:2 did cause a fourfold rise in plasma free linoleate. Quantitation of long chain acyl CoA esters in freeze-clamped liver tissue of rats fed fat-free or fat-free plus 3% C_18:2 or C_18:3 diets revealed no concentration differences between treatments either before or after a meal. Similarly, lactate and pyruvate concentrations as well as the lactate:pyruvate ratios were not significantly changed by dietary C_18:2 or C_18:3. The inhibitory effects of C_18:2 or C_18:3 appear not to be mediated through changes in total plasma free fatty acid levels, in total hepatic long chain acyl CoA concentration or in hepatic cytosolic redox state.