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

Glucose and fatty acid metabolism (oxidation versus esterification) has bee n measured in hepatocytes isolated from 24 h starved peroxisome proliferato r-activated receptor-alpha (PPAR alpha) null and wild-type mice. In PPAR al pha null mice, the development of hypoglycemia during starvation was due to a reduced capacity for hepatic gluconeogenesis secondary to a 70% lower ra te 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 impair ed mitochondrial hydroxymethylglutaryl-CoA synthase gene expression in the PPAR alpha null mouse liver. We also demonstrate that hepatic steatosis of fasting PPAR alpha null mice was not due to enhanced triglyceride synthesis . (C) 2000 Federation of European Biochemical Societies. Published by Elsev ier Science B.V. All rights reserved.