Betaine–homocysteine methyltransferase promotes adipocyte commitment and insulin resistance via p38 MAPK/Smad signaling

IF 4.2 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Obesity Pub Date : 2023-05-19 DOI:10.1002/oby.23737

Chuchu Liu, Yao Zhang, Yanping Wang, Ning Wang, Junting Xu, Xingxing Liang, Jie Xiong, Sijia Lu, Peihui Zhou, Junli Liu, Suzhen Chen

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引用次数: 0

Abstract

Objective

Betaine–homocysteine methyltransferase (Bhmt) belongs to the family of methyltransferases and is involved in the one-carbon metabolic cycle, which is associated with the risk of diabetes and adiposity. This study aimed to explore whether Bhmt participated in the development of obesity or its associated diabetes, as well as the mechanism involved.

Methods

The expression levels of Bhmt were examined in stromal vascular fraction cells and mature adipocytes in obesity and nonobesity. Knockdown and overexpression of Bhmt in C3H10T1/2 cells were used to investigate Bhmt's function in adipogenesis. Bhmt's role in vivo was analyzed using an adenovirus-expressing system and a high-fat diet–induced obesity mouse model.

Results

Bhmt was highly expressed in stromal vascular fraction cells rather than mature adipocytes of adipose tissue and was upregulated in adipose tissue in obesity and C3H10T1/2-commited preadipocytes. Overexpression of Bhmt promoted adipocyte commitment and differentiation in vitro and exacerbated adipose tissue expansion in vivo, with a concomitant increase in insulin resistance, whereas Bhmt silencing exhibited opposite effects. Mechanistically, Bhmt-induced adipose expansion was mediated by stimulating the p38 MAPK/Smad pathway.

Conclusions

The findings of this study highlight the obesogenic and diabetogenic role of adipocytic Bhmt and propose Bhmt as a promising therapeutic target for obesity and obesity-related diabetes.

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甜菜碱-同型半胱氨酸甲基转移酶通过p38 MAPK/Smad信号传导促进脂肪细胞承诺和胰岛素抵抗

目的甜菜碱-同型半胱氨酸甲基转移酶(Bhmt)属于甲基转移酶家族，参与单碳代谢循环，与糖尿病和肥胖风险相关。本研究旨在探讨Bhmt是否参与肥胖及其相关糖尿病的发生及其机制。方法检测肥胖和非肥胖大鼠间质血管部分细胞和成熟脂肪细胞中Bhmt的表达水平。通过在C3H10T1/2细胞中敲低Bhmt和过表达Bhmt来研究Bhmt在脂肪形成中的作用。利用腺病毒表达系统和高脂饮食诱导的肥胖小鼠模型分析Bhmt在体内的作用。结果Bhmt在脂肪组织的间质血管部分细胞而非成熟脂肪细胞中高表达，在肥胖和c3h10t1 /2型前脂肪细胞的脂肪组织中表达上调。在体外，Bhmt的过表达促进了脂肪细胞的承诺和分化，并加剧了体内脂肪组织的扩张，同时增加了胰岛素抵抗，而Bhmt的沉默则表现出相反的效果。在机制上，bhmt诱导的脂肪扩张是通过刺激p38 MAPK/Smad通路介导的。结论本研究结果强调了脂肪细胞化Bhmt的致肥和致糖尿病作用，并提出Bhmt是肥胖和肥胖相关糖尿病的有希望的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Obesity 医学-内分泌学与代谢

CiteScore

11.70

自引率

1.40%

发文量

261

审稿时长

2-4 weeks

期刊介绍： Obesity is the official journal of The Obesity Society and is the premier source of information for increasing knowledge, fostering translational research from basic to population science, and promoting better treatment for people with obesity. Obesity publishes important peer-reviewed research and cutting-edge reviews, commentaries, and public health and medical developments.