SOX4 Regulates Thermogenesis in Brown Adipose Tissue via Independent Complexes with EBF2 and PPARγ.

IF 2.6 3区 生物学 Q3 MATERIALS SCIENCE, BIOMATERIALS
Shuai Wang, Ting He, Tong Fu, Yu Zhu, Yixin Wei, Wenlong Xie, Huanming Shen, Ya Luo, Boan Li, Huiling Guo, Weihua Li
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Abstract

Brown adipose tissue (BAT) is crucial for maintaining whole-body metabolic homeostasis and combating obesity and metabolic disorders. SOX4 collaborates with EBF2 to promote the expression of thermogenic genes in BAT, but it is unclear whether there are mechanisms independent of this regulation. However, it is found that SOX4 can directly interact with the promoter regions of thermogenic genes, thereby activating their expression. Simultaneously, early B cell factor 2 (EBF2) and peroxisome proliferator-activated receptor-γ (PPARγ) can independently interact with SOX4, forming two distinct complexes that promote the expression of thermogenic genes. Phenotypically, the deletion of SOX4 in BAT of mice (Ucp1Cre+-Sox4f/f (Sox4-BKO)) leads to the downregulation of thermogenic and oxidative phosphorylation genes, as well as a reduction in mitochondrial numbers. Furthermore, Sox4-BKO mice are more susceptible to obesity, glucose intolerance, and insulin resistance when subjected to a high-fat diet (HFD). Consistently, the loss of SOX4 results in increased cellular triglyceride content and reduced expression levels of thermogenic genes in vitro. Together, a novel mechanism by which SOX4 regulates thermogenesis in BAT is elucidated, offering a promising strategy to address obesity and metabolic disorders.

SOX4通过与EBF2和PPARγ的独立复合物调节棕色脂肪组织的产热作用。
棕色脂肪组织(BAT)对于维持全身代谢稳态和对抗肥胖和代谢紊乱至关重要。SOX4与EBF2协同促进BAT中产热基因的表达,但是否存在独立于此调控的机制尚不清楚。然而,研究发现SOX4可以直接与产热基因的启动子区相互作用,从而激活其表达。同时,早期B细胞因子2 (EBF2)和过氧化物酶体增殖激活受体-γ (PPARγ)可以独立地与SOX4相互作用,形成两种不同的复合物,促进产热基因的表达。表型上,小鼠BAT中SOX4 (Ucp1Cre+-Sox4f/f (SOX4 - bko))的缺失导致产热和氧化磷酸化基因的下调,以及线粒体数量的减少。此外,Sox4-BKO小鼠在接受高脂肪饮食(HFD)时更容易发生肥胖、葡萄糖耐受不良和胰岛素抵抗。同样,SOX4的缺失导致细胞甘油三酯含量增加,体外产热基因表达水平降低。总之,SOX4调控BAT产热的新机制被阐明,为解决肥胖和代谢紊乱提供了一个有希望的策略。
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
Advanced biology
Advanced biology Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
6.60
自引率
0.00%
发文量
130
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