胰岛素抵抗
脂肪肝
线粒体
氧化应激
肥胖
脂肪组织
生物
非酒精性脂肪肝
脂肪变性
脂肪酸合酶
脂肪酸代谢
氧化磷酸化
生物化学
CD36
脂质代谢
作者
Jieun Lee,Joseph Choi,Ebru S. Selen Alpergin,Liang Zhao,Thomas Hartung,Susanna Scafidi,Ryan C. Riddle,Michael J. Wolfgang
出处
期刊:Cell Reports
[Elsevier]
日期:2017-07-18
卷期号:20 (3): 655-667
被引量:44
标识
DOI:10.1016/j.celrep.2017.06.080
摘要
Summary 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.
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