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

Lee, Jieun; Choi, Joseph; Selen Alpergin, Ebru S.; Zhao, Liang; Hartung, Thomas; Scafidi, Susanna; Riddle, Ryan C.; Wolfgang, Michael J.

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

Dateien

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Datum

2017

Autor:innen

Lee, Jieun

Choi, Joseph

Selen Alpergin, Ebru S.

Zhao, Liang

Hartung, Thomas

Scafidi, Susanna

Riddle, Ryan C.

Wolfgang, Michael J.

Open Access-Veröffentlichung

Open Access Gold

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Cell Reports. 2017, 20(3), pp. 655-667. eISSN 2211-1247. Available under: doi: 10.1016/j.celrep.2017.06.080

Zusammenfassung

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 (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.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Schlagwörter

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

Zitieren

ISO 690

LEE, Jieun, Joseph CHOI, Ebru S. SELEN ALPERGIN, Liang ZHAO, Thomas HARTUNG, Susanna SCAFIDI, Ryan C. RIDDLE, Michael J. WOLFGANG, 2017. Loss of Hepatic Mitochondrial Long-Chain Fatty Acid Oxidation Confers Resistance to Diet-Induced Obesity and Glucose Intolerance. In: Cell Reports. 2017, 20(3), pp. 655-667. eISSN 2211-1247. Available under: doi: 10.1016/j.celrep.2017.06.080

BibTex

@article{Lee2017-07Hepat-40340,
  year={2017},
  doi={10.1016/j.celrep.2017.06.080},
  title={Loss of Hepatic Mitochondrial Long-Chain Fatty Acid Oxidation Confers Resistance to Diet-Induced Obesity and Glucose Intolerance},
  number={3},
  volume={20},
  journal={Cell Reports},
  pages={655--667},
  author={Lee, Jieun and Choi, Joseph and Selen Alpergin, Ebru S. and Zhao, Liang and Hartung, Thomas and Scafidi, Susanna and Riddle, Ryan C. and Wolfgang, Michael J.}
}

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    <dcterms:abstract xml:lang="eng">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 (Cpt2&lt;sup&gt;L-/-&lt;/sup&gt; mice). Paradoxically, Cpt2&lt;sup&gt;L-/-&lt;/sup&gt; 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.</dcterms:abstract>
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