Branched Chain Amino Acids Cause Liver Injury in Obese/Diabetic Mice by Promoting Adipocyte Lipolysis and Inhibiting Hepatic Autophagy

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• 作者：Fuyang Zhang^a ; ¹ ; Shihao Zhao^a ; ¹ ; Wenjun Yan^a ; ¹ ; Yunlong Xia^a ; Xiyao Chen^b ; Wei Wang^a ; Jinglong Zhang^a ; Chao Gao^a ; Cheng Peng^a ; Feng Yan^a ; Huishou Zhao^a ; Kun Lian^a ; Yan Lee^a ; Ling Zhang^a ; Wayne Bond Lau^c ; Xinliang Ma^c ; Ling Tao^a ; ^{lingtao@fmmu.edu.cn}
• 刊名：EBioMedicine
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：13
• 期：Complete
• 页码：157-167
• 全文大小：1530 K
• 卷排序：13

文摘

BCAA cause hepatic injury via complex mechanisms involving both adipocytes and hepatic cells. In the adipocyte, BCAA activate AMPKα2 and stimulate lipolysis, increasing plasma free fatty acids (FFA), which in turn results in hepatic FFA accumulation. In the liver, BCAA activate mTOR and inhibit FFA to TG conversion and autophagy, intensifying FFA lipotoxicity.High fat diet (HFD) induces systemic BCAA catabolic defects. Under HFD conditions, increased BCAA consumption further increases circulating BCAA abundance. BCAA-enhanced adipocyte lipolysis induces hyperlipidemia through activating AMPKα2. Elevated circulating FFA results in insulin resistance and hepatic lipotoxicity. Moreover, BCAA activate hepatic mTOR, inhibit lipogenesis and autophagy, therefore increasing hepatic susceptibility to FFA-mediated lipotoxicity. As BCAA are abundant in protein, our results call for caution regarding the ingestion of high protein diets in obesity and diabetic individuals, unless their BCAA metabolic pathways are determined normal.