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丙糖激酶控制果糖的脂肪生成潜能和饮食耐受性
2020-08-21 22:06

清华大学傅肃能研究组发现,丙糖激酶控制果糖的脂肪生成潜能和饮食耐受性。2020年8月19日,《细胞—代谢》杂志在线发表了这项成果。

通过代谢流和遗传分析,研究人员证明果糖的分解代谢速率比葡萄糖高得多,并且丙糖激酶(TK)将果糖分解与脂肪代谢和转录过程耦合在一起。在没有TK的情况下,果糖的氧化通过醛脱氢酶(ALDH)的激活和丝氨酸的生物合成而加速,并伴随着氧化应激的增加和果糖的厌恶。内源性果糖分解途径还需要TK,从而在高脂饮食和瘦素缺乏的条件下驱动脂肪生成和肝甘油三酸酯积累。
 
有趣的是,在人类移出非洲期间出现一个非同义TK等位基因(rs2260655_A),由于无法挽救果糖毒性并增加肝甘油三酸酯的积累,从而表现为TK缺失表型。因此,研究人员认为TK是一个代谢转换枢纽,参与控制果糖的脂肪形成潜力和饮食耐受性。
 
据悉,果糖消费的激增是现代社会非酒精性脂肪肝疾病迅速上升的主要因素。
 
附:英文原文

Title: Triose Kinase Controls the Lipogenic Potential of Fructose and Dietary Tolerance

Author: Lei Liu, Tian Li, Yilie Liao, Yalong Wang, Yang Gao, Haikun Hu, Haipeng Huang, Fang Wu, Ye-Guang Chen, Shuhua Xu, Suneng Fu

Issue&Volume: 2020-08-19

Abstract: The surge in fructose consumption is a major factor behind the rapid rise of nonalcoholicfatty liver disease in modern society. Through flux and genetic analyses, we demonstratethat fructose is catabolized at a much higher rate than glucose, and triose kinase(TK) couples fructolysis with lipogenesis metabolically and transcriptionally. Inthe absence of TK, fructose oxidation is accelerated through the activation of aldehydedehydrogenase (ALDH) and serine biosynthesis, accompanied by increased oxidative stressand fructose aversion. TK is also required by the endogenous fructolysis pathway todrive lipogenesis and hepatic triglyceride accumulation under high-fat diet and leptin-deficientconditions. Intriguingly, a nonsynonymous TK allele (rs2260655_A) segregated during human migration out of Africa behaves as TK null for its inabilityto rescue fructose toxicity and increase hepatic triglyceride accumulation. Therefore,we posit TK as a metabolic switch controlling the lipogenic potential of fructose and its dietary tolerance.

DOI: 10.1016/j.cmet.2020.07.018

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30413-7

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:31.373
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx


本期文章:《细胞—代谢》:Online/在线发表

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