Reduced hepatic fatty acid oxidation in fasting PPARα null mice is due to impaired mitochondrial hydroxymethylglutaryl-CoA synthase gene expression

AbstractGlucose and fatty acid metabolism (oxidation versus esterification) has been measured in hepatocytes isolated from 24 h starved peroxisome proliferator-activated receptor-α (PPARα) null and wild-type mice. In PPARα null mice, the development of hypoglycemia during starvation was due to a reduced capacity for hepatic gluconeogenesis secondary to a 70% lower rate of fatty acid oxidation. This was not due to inappropriate expression of the hepatic CPT I gene, which was similar in both genotypes, but to impaired mitochondrial hydroxymethylglutaryl-CoA synthase gene expression in the PPARα null mouse liver. We also demonstrate that hepatic steatosis of fasting PPARα null mice was not due to enhanced triglyceride synthesis