KETONE-BODY UTILIZATION FOR LIPOGENESIS IN THE PERFUSED LIVER OF THE OBESE ZUCKER RAT

The purpose of these studies was to determine if the utilization of ketone bodies as a carbon source for lipogenesis could account for the decreased ketone body production by livers of obese Zucker rats, as well as contribute to the enhanced rates of fatty acid synthesis observed in these animals. Ketone body production was decreased from 822 μmol/liver in the lean to 538 μmol/liver in the obese genotype (P < 0.05). The incorporation of ketone bodies into fatty acids was significantly greater in the obese rat liver (lean, 1.95 μmol of ketone bodies/liver, versus obese, 35.22 μmol/liver; P < 0.025). The relative contribution of this pathway to the overall rate of fatty acid synthesis was not affected by genotype and accounted for only 3 to 4% of the fatty acids synthesized. The incorporation of ketone bodies into digitonin precipitable sterols was similar in the two genotypes (lean, 4.5 mmol/liver, versus obese 4.7 μmol/liver; NS). This accounted for 9.2 and 6.3% of the total sterol synthesis in lean and obese rat livers, respectively. The total incorporation of ketone bodies into lipid was 7.5 μmols in the lean rat livers and 42.0 μmoles in the obese (P < 0.025). The net increase was 35 μmoles incorporated, whereas the net decrease in ketogenesis was 284 μmoles. Thus, although ketone body carbon utilization for lipid synthesis was increased in the liver of the obese rats, this pathway could only account for a fraction of the genotypic difference in ketone body production and was of relatively minor importance as a source of carbon for hepatic fatty acid synthesis in both lean and obese rats.