Lipophagy mediate d glucose-induced changes of lipid deposition and metabolism via ROS dependent AKT-Beclin1 activation

文献类型： 外文期刊

第一作者： Wu, Li-Xiang

作者： Wu, Li-Xiang;Xu, Yi-Chuang;Zhao, Tao;Wu, Kun;Xu, Yi-Huan;Luo, Zhi;Hogstrand, Christer;Liu, Wei

作者机构：

关键词： Dietary carbohydrate; Lipid accumulation; Lipid metabolism; Lipoophagy; Molecular mechanism

期刊名称：JOURNAL OF NUTRITIONAL BIOCHEMISTRY （ 影响因子：6.117； 五年影响因子：6.287 ）

ISSN： 0955-2863

年卷期： 2022 年 100 卷

页码：

收录情况： SCI

摘要： High dietary carbohydrate intake leads to lipid accumulation in the intestinal tract, but the molecular mechanism remains unknown. In the present study, using yellow catfish (Pelteobagrus fulvidraco) as a model, we found that (1) high carbohydrate diets (HCD) and high glucose (HG) increased lipid deposition, up-regulated lipogenesis and fatty acid beta-oxidation, activated autophagy and induced oxidative stress in the intestinal tissues and intestinal epithelial cells (IECs); (2) lipophagy alleviated HG-induced lipid accumulation via the up-regulation of fatty acid beta-oxidation; (3) Akt interacted directly with Beclin1; (4) HG suppressed Akt1 phosphorylation, downregulated Akt1-mediated phosphorylation of Beclin1, activated lipophagy and alleviated the increment of TG deposition induced by HG with S87 and S292 being the key phosphorylation residues of Beclin1 in response to HG; (5) ROS generation mediated HG-induced activation of lipophagy and HG-induced suppression of AKT phosphorylation, activated AMPK and alleviated HG-induced increase of TG deposition. Our study provides mechanistic evidence that high carbohydrate-and glucose-induced lipophagy in intestine and IECs is associated with ROS-AKT-Beclin1-dependent activation of autophagy, which alleviates glucose-induced lipid accumulation. Our findings are important since the regulation of autophagy can be used as potential molecular targets for the prevention and treatment of lipotoxicity in the intestine of vertebrates, including humans. (C) 2021 Elsevier Inc. All rights reserved.

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