TY - JOUR
T1 - Hepatic Fatty Acid Oxidation Restrains Systemic Catabolism during Starvation
AU - Lee, Jieun
AU - Choi, Joseph
AU - Scafidi, Susanna
AU - Wolfgang, Michael J.
N1 - Publisher Copyright:
© 2016 The Author(s)
PY - 2016/6/28
Y1 - 2016/6/28
N2 - 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.
AB - 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.
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U2 - 10.1016/j.celrep.2016.05.062
DO - 10.1016/j.celrep.2016.05.062
M3 - Article
C2 - 27320917
AN - SCOPUS:85008406081
SN - 2211-1247
VL - 16
SP - 201
EP - 212
JO - Cell Reports
JF - Cell Reports
IS - 1
ER -