Hepatic Fatty Acid Oxidation Restrains Systemic Catabolism during Starvation.

ABSTRACT: The liver is critical for maintaining systemic energy balance during starvation. To understand the role of hepatic fatty acid β-oxidation on this process, we generated mice with a liver-specific knockout of carnitine palmitoyltransferase 2 (Cpt2(L-/-)), an obligate step in mitochondrial long-chain fatty acid β-oxidation. Fasting induced hepatic steatosis and serum dyslipidemia with an absence of circulating ketones, while blood glucose remained normal. Systemic energy homeostasis was largely maintained in fasting Cpt2(L-/-) mice by adaptations in hepatic and systemic oxidative gene expression mediated in part by Pparα target genes including procatabolic hepatokines Fgf21, Gdf15, and Igfbp1. Feeding a ketogenic diet to Cpt2(L-/-) mice resulted in severe hepatomegaly, liver damage, and death

SUBMITTER: Lee J 

PROVIDER: S-EPMC4927362 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature