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新型植物提取化合物能够通过促进脂肪组织的产热作用来治疗肥胖
作者:小柯机器人 发布时间:2021/3/4 16:06:11

上海市第六人民医院糖尿病研究所刘军力课题组发现,新型植物提取化合物能够通过促进脂肪组织的产热作用来治疗肥胖。相关论文发表在2021年3月2日出版的《细胞—代谢》杂志上。

使用CMap(Connectivity Map)方法,研究人员确定了植物化合物贯叶金丝桃素(HPF)可作为减肥药物。研究人员发现,HPF通过依赖于Ucp1的途径刺激AMPK和PGC-1α,从而有效地促进了产热作用。使用LiP-SMap(有限蛋白水解质谱法)与微尺度热泳分析和分子对接分析相结合,研究人员确认了二氢脂酰胺S-乙酰基转移酶(Dlat)是HPF的直接分子靶标。Dlat的敲除在体外和体内均显著减弱了HPF介导的脂肪组织棕色化。

此外,全基因组关联研究分析表明DLAT的变异与人类肥胖显著相关。这些发现表明,HPF是一种有前途的先导化合物,可用于寻求药理学方法来促进肥胖症治疗中的能量消耗。

据介绍,刺激脂肪组织生热被认为是治疗肥胖的有前途的途径。然而,通过药理学调节该过程是很难的。

附:英文原文

Title: The phytochemical hyperforin triggers thermogenesis in adipose tissue via a Dlat-AMPK signaling axis to curb obesity

Author: Suzhen Chen, Xiaoxiao Liu, Chao Peng, Chang Tan, Honglin Sun, He Liu, Yao Zhang, Ping Wu, Can Cui, Chuchu Liu, Di Yang, Zhiqiang Li, Junxi Lu, Jian Guan, Xisong Ke, Renxiao Wang, Xiaohai Bo, Xiaojun Xu, Junfeng Han, Junli Liu

Issue&Volume: 2021/03/02

Abstract: Stimulation of adipose tissue thermogenesis is regarded as a promising avenue in the treatment of obesity. However, pharmacologic engagement of this process has proven difficult. Using the Connectivity Map (CMap) approach, we identified the phytochemical hyperforin (HPF) as an anti-obesity agent. We found that HPF efficiently promoted thermogenesis by stimulating AMPK and PGC-1α via a Ucp1-dependent pathway. Using LiP-SMap (limited proteolysis-mass spectrometry) combined with a microscale thermophoresis assay and molecular docking analysis, we confirmed dihydrolipoamide S-acetyltransferase (Dlat) as a direct molecular target of HPF. Ablation of Dlat significantly attenuated HPF-mediated adipose tissue browning both in vitro and in vivo. Furthermore, genome-wide association study analysis indicated that a variation in DLAT is significantly associated with obesity in humans. These findings suggest that HPF is a promising lead compound in the pursuit of a pharmacological approach to promote energy expenditure in the treatment of obesity.

DOI: 10.1016/j.cmet.2021.02.007

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00063-2

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx