脱甲基酶
白色脂肪组织
产热
内分泌学
脂肪生成
脂肪组织
脂肪细胞
脂肪组织巨噬细胞
组蛋白
H3K4me3
巨噬细胞
化学
下调和上调
细胞生物学
表观遗传学
锡尔图因
炎症
生物
内科学
基因表达
医学
生物化学
基因
体外
发起人
乙酰化
作者
Jun Chen,Xing Xu,Yan Li,Li Fan,Jianjun Zhang,Qin Xu,Wantao Chen,Wei Yan,Xu Wang
标识
DOI:10.1038/s41418-020-00694-8
摘要
Histone lysine demethylase 6a (Kdm6a) mediates the removal of repressive trimethylation from histone H3 lysine 27 (H3K27me3) to activate target gene expression. Obesity is associated with metabolic inflammation, and adipose tissue macrophages (ATMs) are key players orchestrating metabolic inflammation. However, it is still unclear whether the Kdm6a pathway in ATMs regulates energy homeostasis. Here, we identified Kdm6a as a critical epigenetic switch that modulates macrophage polarisation and further disrupts energy balance. Myeloid-specific Kdm6a knockout in Kdm6aF/Y;Lyz2-Cre mice significantly reversed the high-fat diet (HFD)-induced M1-M2 imbalance in white adipose tissue (WAT) and blocked HFD-induced obesity. The brown adipose tissue (BAT) activity, WAT browning and energy expenditure were significantly increased in Kdm6aF/Y;Lyz2-Cre mice. Furthermore, Kdm6a regulated the Ire1α expression in a demethylase activity-dependent manner and augmented the M2 polarisation of macrophages. Macrophage with higher Kdm6a significantly promotes adipogenesis in white adipocyte and inhibits thermogenesis in beige adipocytes. These results suggest that the Kdm6a in macrophages drives obesity and metabolic syndrome by impairing BAT activity and WAT differentiation.
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