The effect of fructose on hepatic synthesis of fatty acids.

Abstract

Abstract. The synthesis of fatty acids from fructose and glucose has been compared in rat and human liver. In both species fructose is a better precursor of fatty acids than glucose, primarily as a result of the greater rate of glycolysis of fructose as compared to glucose. The high rate of fructose utilization and relatively low rates of glucose utilization by liver is reflected by the activity of fructokinase which is considerably greater than the total hexokinase and glucokinase activities. Although it is not possible to exclude that the high rate of fructolysis produces a metabolic intermediate which alters the functional state of the fatty acid synthesizing enzymes, the experimental evidence indicates that hepatic fatty acid synthesis in carbohydrate‐fed animals is limited by the supply of substrate. Because the hepatic metabolism of fructose can supply acetyl CoA to the fatty acid synthesizing enzymes at greater rates than can glucose, hepatic fatty acid synthesis is enhanced in fructose‐ or sucrose‐fed animals. Since estimates of maximum rates of fatty acid synthesis in human liver based on in vitro measurement of the activity of acetyl‐CoA carboxylase suggest that de novo synthesis of fatty acids in human liver can be large in comparison to the turnover of triglycerides in very low density lipoproteins, the data are compatible with the conclusion that enhanced rates of hepatic fatty acid synthesis contribute significantly to fructose‐ or sucrose‐induced hypertriglyceridemia in normal men.