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FNDC5 Alleviates Hepatosteatosis by Restoring AMPK/mTOR-Mediated Autophagy, Fatty Acid Oxidation, and Lipogenesis in Mice.
Liu, Tong-Yan; Xiong, Xiao-Qing; Ren, Xing-Sheng; Zhao, Ming-Xia; Shi, Chang-Xiang; Wang, Jue-Jin; Zhou, Ye-Bo; Zhang, Feng; Han, Ying; Gao, Xing-Ya; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing.
Afiliación
  • Liu TY; Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China.
  • Xiong XQ; Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China.
  • Ren XS; Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China.
  • Zhao MX; Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China.
  • Shi CX; Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China.
  • Wang JJ; Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China.
  • Zhou YB; Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China.
  • Zhang F; Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China.
  • Han Y; Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China.
  • Gao XY; Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China.
  • Chen Q; Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu, China.
  • Li YH; Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu, China.
  • Kang YM; Department of Physiology and Pathophysiology, Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
  • Zhu GQ; Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China gqzhucn@njmu.edu.cn.
Diabetes ; 65(11): 3262-3275, 2016 Nov.
Article en En | MEDLINE | ID: mdl-27504012
Fibronectin type III domain-containing 5 (FNDC5) protein induces browning of subcutaneous fat and mediates the beneficial effects of exercise on metabolism. However, whether FNDC5 is associated with hepatic steatosis, autophagy, fatty acid oxidation (FAO), and lipogenesis remains unknown. Herein, we show the roles and mechanisms of FNDC5 in hepatic steatosis, autophagy, and lipid metabolism. Fasted FNDC5-/- mice exhibited severe steatosis, reduced autophagy, and FAO, and enhanced lipogenesis in the liver compared with wild-type mice. Energy deprivation-induced autophagy, FAO, and AMPK activity were attenuated in FNDC5-/- hepatocytes, which were restored by activating AMPK with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). Inhibition of mammalian target of rapamycin (mTOR) complex 1 with rapamycin enhanced autophagy and FAO and attenuated lipogenesis and steatosis in FNDC5-/- livers. FNDC5 deficiency exacerbated hyperlipemia, hepatic FAO and autophagy impairment, hepatic lipogenesis, and lipid accumulation in obese mice. Exogenous FNDC5 stimulated autophagy and FAO gene expression in hepatocytes and repaired the attenuated autophagy and palmitate-induced steatosis in FNDC5-/- hepatocytes. FNDC5 overexpression prevented hyperlipemia, hepatic FAO and autophagy impairment, hepatic lipogenesis, and lipid accumulation in obese mice. These results indicate that FNDC5 deficiency impairs autophagy and FAO and enhances lipogenesis via the AMPK/mTOR pathway. FNDC5 deficiency aggravates whereas FNDC5 overexpression prevents the HFD-induced hyperlipemia, hepatic lipid accumulation, and impaired FAO and autophagy in the liver.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fibronectinas / Proteínas Quinasas Activadas por AMP / Proteína 5 Relacionada con la Autofagia Límite: Animals Idioma: En Revista: Diabetes Año: 2016 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Buscar en Google
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PubMed Links

Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fibronectinas / Proteínas Quinasas Activadas por AMP / Proteína 5 Relacionada con la Autofagia Límite: Animals Idioma: En Revista: Diabetes Año: 2016 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos