Mechanism for the differential effects of high carbohydrate diets on lipogenesis in rat liver

Abstract

1. 1. The changes in the hepatic concentration of glycolytic and tricarboxylic acid cycle intermediates, the conversion of [ 14C 6]glucose and [ 14C 6]fructose to fatty acids and CO 2 in liver slices, and the activity of certain lipogenic and glycolytic enzymes in the liver have been compared in fasted rats refed a chow diet or diets high in glucose or fructose content. These measurements have been correlated with the effects of the different diets on the hepatic and serum triglyceride concentration. 2. 2. The animals fed the fructose diet had the highest hepatic and serum triglyceride concentrations whereas the chow-fed animals had the lowest. 3. 3. Several differences were noted between fructose, glucose or chow-fed rats in the concentration of glycolytic and tricarboxylic acid cycle intermediates. Most important, fructose feeding was associated with a greater hepatic concentration of pyruvate, CoASAc and malate than in either the glucose or chow-fed groups. The conversion of [ 14C 6]fructose to fatty acids was increased by either the fructose or glucose diet in comparison to the chow diet. Further, in each dietary group more [ 14C 6]fructose than [ 14C 6]glucose was incorporated into fatty acids, indicating that the synthesis of hepatic fatty acids from glucose was not limited by the activity of the fatty acid synthesizing enzymes. 4. 4. The activity of fructokinase (ATP : d-fructose 1-phosphotransferase, EC 2.7.1.3) was greater than that of glucokinase (ATP : d-glucose 6-phosphotransf erase, EC 2.7.1.2) and hexokinase (ATP : d-glucose 6-phosphotransferase, EC 2.7.1.1) in all diet groups. As a result more fructose than glucose could be phosphorylated in rat liver. In comparison to the chow-fed rats the hepatic CoASAc-carboxylase (CoASAc : carbon-dioxide ligase (ADP), EC 6.4.1.2) activity was increased to the same extent by the fructose or glucose feeding. 5. 5. It is concluded that the mechanism for the differential effects of high carbohydrate diets on hepatic fatty acid synthesis depends upon the higher rate of CoASAc formation from fructose as compared to glucose. The difference m the activity for the glucose and fructose phosphorylating enzymes in rat liver could account for the different rates at which fructose and glucose were metabolized to CoASAc. A secondary effect is that either a high glucose or fructose diet increases the hepatic activity of CoASAc carboxylase.