Requirement of hepatic pyruvate carboxylase during fasting, high fat, and ketogenic diet.

ABSTRACT: Pyruvate has two major fates upon entry into mitochondria, the oxidative decarboxylation to acetyl-CoA via the pyruvate decarboxylase complex or the biotin-dependent carboxylation to oxaloacetate via pyruvate carboxylase (Pcx). Here, we have generated mice with a liver-specific KO of pyruvate carboxylase (Pcx^L-/-) to understand the role of Pcx in hepatic mitochondrial metabolism under disparate physiological states. Pcx^L-/- mice exhibited a deficit in hepatic gluconeogenesis and enhanced ketogenesis as expected but were able to maintain systemic euglycemia following a 24 h fast. Feeding a high-fat diet to Pcx^L-/- mice resulted in animals that were resistant to glucose intolerance without affecting body weight. However, we found that Pcx^L-/- mice

SUBMITTER: Selen ES 

PROVIDER: S-EPMC9694104 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature