瘦素
脂肪细胞
内分泌学
内科学
表观遗传学
脂肪因子
脂肪组织
生物
产热
能量稳态
肥胖
基因
医学
遗传学
作者
Qiandong Zeng,Jiaojiao Song,Xiaoxiao Sun,Dandan Wang,Xiyan Liao,Yujin Ding,Wanyu Hu,Yuanyuan Jiao,Wuqian Mai,Wufuer Aini,Fanqi Wang,Hui Zhou,Lihua Xie,Ying Mei,Yuan Tang,Zhiguo Xie,Haijing Wu,Wei Liu,Tuo Deng
标识
DOI:10.1038/s41467-024-46783-x
摘要
Ten-eleven translocation (TET) 2 is an enzyme that catalyzes DNA demethylation to regulate gene expression by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine, functioning as an essential epigenetic regulator in various biological processes. However, the regulation and function of TET2 in adipocytes during obesity are poorly understood. In this study, we demonstrate that leptin, a key adipokine in mammalian energy homeostasis regulation, suppresses adipocyte TET2 levels via JAK2-STAT3 signaling. Adipocyte Tet2 deficiency protects against high-fat diet-induced weight gain by reducing leptin levels and further improving leptin sensitivity in obese male mice. By interacting with C/EBPα, adipocyte TET2 increases the hydroxymethylcytosine levels of the leptin gene promoter, thereby promoting leptin gene expression. A decrease in adipose TET2 is associated with obesity-related hyperleptinemia in humans. Inhibition of TET2 suppresses the production of leptin in mature human adipocytes. Our findings support the existence of a negative feedback loop between TET2 and leptin in adipocytes and reveal a compensatory mechanism for the body to counteract the metabolic dysfunction caused by obesity.
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