Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Cell Rep. 2017 Jul 18;20(3):655-667. doi: 10.1016/j.celrep.2017.06.080.

Loss of Hepatic Mitochondrial Long-Chain Fatty Acid Oxidation Confers Resistance to Diet-Induced Obesity and Glucose Intolerance.

Author information

1
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2
Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
3
Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Biology, University of Konstanz, 78464 Konstanz, Germany.
4
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
5
Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Baltimore Veterans Administration Medical Center, Baltimore, MD 21201, USA.
6
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: mwolfga1@jhmi.edu.

Abstract

The liver has a large capacity for mitochondrial fatty acid β-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 β-oxidation (Cpt2L-/- mice). Paradoxically, Cpt2L-/- 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.

KEYWORDS:

Fgf21; Gdf15; NAFLD; NASH; diabetes; fatty acid oxidation; gluconeogenesis; hormesis; ketogenesis; obesity; steatosis

PMID:
28723568
PMCID:
PMC5546239
DOI:
10.1016/j.celrep.2017.06.080
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center