Loss of Hepatic Mitochondrial Long-Chain Fatty Acid Oxidation Confers Resistance to Diet-Induced Obesity and Glucose Intolerance.
Loss of Hepatic Mitochondrial Long-Chain Fatty Acid Oxidation Confers Resistance to Diet-Induced Obesity and Glucose Intolerance.
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DOI：
10.1016/j.celrep.2017.06.080
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发表时间：
2017-07-18
期刊：
影响因子：
8.8
通讯作者：
Wolfgang MJ
中科院分区：
文献类型：
--
作者：
Lee J;Choi J;Selen Alpergin ES;Zhao L;Hartung T;Scafidi S;Riddle RC;Wolfgang MJ
肝脏具有很大的线粒体脂肪酸β氧化能力，这对糖异生和酮生等系统代谢适应至关重要。为了了解肝脏脂肪酸氧化在慢性高脂饮食反应中的作用，我们培育了肝脏特异性线粒体长链脂肪酸β氧化缺陷小鼠(Cpt2L−/−小鼠)。矛盾的是，Cpt2L−/−小鼠虽然表现出血清血脂异常、肝脏氧化应激和全身性肉碱缺乏，但对高脂饮食诱导的肥胖和糖耐量异常具有抵抗力，并且没有肝脏损伤。喂食高脂饮食可导致小鼠肝脏脂肪酸氧化丧失，从而增加全身能量消耗并抑制肥胖。此外，对肝脏糖异生的抑制足以改善HFD诱导的葡萄糖耐量。这些数据表明，抑制肝脏脂肪酸氧化会导致全身兴奋反应，保护小鼠免受高脂饮食诱导的肥胖和糖耐量异常的影响。Lee等人。研究表明，与预期相反，肝脏脂肪酸氧化(FAO)的丧失可以抵抗高脂肪饮食导致的体重增加和肥胖。此外，他们还表明，失去肝脏粮农组织，从而肝脏糖异生，保护小鼠免受高脂饮食诱导的葡萄糖耐受。
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 a 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. Lee et al. show that contrary to expectations, the loss of hepatic fatty acid oxidation (FAO) confers resistance to weight gain and adiposity in response to a high fat diet. Additionally, they show that loss of heptic FAO, and consequently hepatic gluconeogenesis, protects mice from high fat diet-induced glucose intolerance.
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影响因子：
29
作者：
Perry RJ;Kim T;Zhang XM;Lee HY;Pesta D;Popov VB;Zhang D;Rahimi Y;Jurczak MJ;Cline GW;Spiegel DA;Shulman GI
通讯作者：
Shulman GI
影响因子：
64.8
作者：
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影响因子：
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影响因子：
15.9
作者：
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通讯作者：
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影响因子：
5.3
作者：
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通讯作者：
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