Hepatic Fatty Acid Oxidation Restrains Systemic Catabolism during Starvation

Jieun Lee, Joseph Choi, Susanna Scafidi, Michael J. Wolfgang

Research output: Contribution to journalArticlepeer-review

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 (Cpt2L−/−), 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 Cpt2L−/− 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 Cpt2L−/− mice resulted in severe hepatomegaly, liver damage, and death with a complete absence of adipose triglyceride stores. These data show that hepatic fatty acid oxidation is not required for survival during acute food deprivation but essential for constraining adipocyte lipolysis and regulating systemic catabolism when glucose is limiting.

Original languageEnglish (US)
Pages (from-to)201-212
Number of pages12
JournalCell Reports
Volume16
Issue number1
DOIs
StatePublished - Jun 28 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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