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Publication : Hepatic Fatty Acid Oxidation Restrains Systemic Catabolism during Starvation.

First Author  Lee J Year  2016
Journal  Cell Rep Volume  16
Issue  1 Pages  201-212
PubMed ID  27320917 Mgi Jnum  J:238370
Mgi Id  MGI:5819169 Doi  10.1016/j.celrep.2016.05.062
Citation  Lee J, et al. (2016) Hepatic Fatty Acid Oxidation Restrains Systemic Catabolism during Starvation. Cell Rep 16(1):201-12
abstractText  The liver is critical for maintaining systemic energy balance during starvation. To understand the role of hepatic fatty acid beta-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 beta-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 Pparalpha 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 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.
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