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Publication
Loss of Hepatic Mitochondrial Long-Chain Fatty Acid Oxidation Confers Resistance
to Diet-Induced Obesity and Glucose Intolerance.
Authors Lee J, Choi J, Selen Alpergin ES, Zhao L, Hartung T, Scafidi S, Riddle RC,
Wolfgang MJ
Submitted By Submitted Externally on 8/17/2017
Status Published
Journal Cell reports
Year 2017
Date Published
Volume : Pages 20 : 655 - 667
PubMed Reference 28723568
Abstract The liver has a large capacity for mitochondrial fatty acid ß-oxidation, which
is critical for systemic metabolic adaptations such as gluconeogenesis and
ketogenesis. To understand the role of hepatic fatty acid oxidation in response
to a chronic high-fat diet (HFD), we generated mice with a liver-specific
deficiency of mitochondrial long-chain fatty acid ß-oxidation (Cpt2(L-/-) mice).
Paradoxically, Cpt2(L-/-) mice were resistant to HFD-induced obesity and glucose
intolerance with an absence of liver damage, although they exhibited serum
dyslipidemia, hepatic oxidative stress, and systemic carnitine deficiency.
Feeding an HFD induced hepatokines in mice, with a loss of hepatic fatty acid
oxidation that enhanced systemic energy expenditure and suppressed adiposity.
Additionally, the suppression in hepatic gluconeogenesis was sufficient to
improve HFD-induced glucose intolerance. These data show that inhibiting hepatic
fatty acid oxidation results in a systemic hormetic response that protects mice
from HFD-induced obesity and glucose intolerance.






Genes
SymbolDescription
Cpt2carnitine palmitoyltransferase 2

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