State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
Cell Death Dis. 2021 Jul 2;12(7):666. doi: 10.1038/s41419-021-03959-3.
High-mobility group box 2 (HMGB2) is an abundant, chromatin-associated protein that plays an essential role in the regulation of transcription, cell proliferation, differentiation, and tumorigenesis. However, the underlying mechanism of HMGB2 in adipogenesis remains poorly known. Here, we provide evidence that HMGB2 deficiency in preadipocytes impedes adipogenesis, while overexpression of HMGB2 increases the potential for adipogenic differentiation. Besides, depletion of HMGB2 in vivo caused the decrease in body weight, white adipose tissue (WAT) mass, and adipocyte size. Consistently, the stromal vascular fraction (SVF) of adipose tissue derived from hmgb2 mice presented impaired adipogenesis. When hmgb2 mice were fed with high-fat diet (HFD), the body size, and WAT mass were increased, but at a lower rate. Mechanistically, HMGB2 mediates adipogenesis via enhancing expression of C/EBPβ by binding to its promoter at "GGGTCTCAC" specifically during mitotic clonal expansion (MCE) stage, and exogenous expression of C/EBPβ can rescue adipogenic abilities of preadipocytes in response to HMGB2 inhibition. In general, our findings provide a novel mechanism of HMGB2-C/EBPβ axis in adipogenesis and a potential therapeutic target for obesity.
高迁移率族蛋白 B2（HMGB2）是一种丰富的染色质相关蛋白，在转录调控、细胞增殖、分化和肿瘤发生中起着至关重要的作用。然而，HMGB2 在脂肪生成中的潜在机制仍知之甚少。在这里，我们提供的证据表明，前脂肪细胞中 HMGB2 的缺失会阻碍脂肪生成，而过表达 HMGB2 则会增加脂肪生成分化的潜力。此外，体内 HMGB2 的耗竭会导致体重、白色脂肪组织（WAT）质量和脂肪细胞大小减少。一致地，来自 hmgb2 小鼠的脂肪组织基质血管部分（SVF）呈现出受损的脂肪生成。当 hmgb2 小鼠喂食高脂肪饮食（HFD）时，其体型和 WAT 质量增加，但增加速度较慢。从机制上讲，HMGB2 通过在有丝分裂克隆扩增（MCE）阶段特异性地结合到其启动子上的“GGGTCTCAC”来增强 C/EBPβ 的表达，从而介导脂肪生成，并且外源性表达 C/EBPβ 可以挽救前脂肪细胞对 HMGB2 抑制的脂肪生成能力。总的来说，我们的研究结果为 HMGB2-C/EBPβ 轴在脂肪生成中的作用提供了一个新的机制，并为肥胖症提供了一个潜在的治疗靶点。
