Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
Neurovascular Unit Research Group, Korea Brain Research Institute, Daegu, Korea.
Cell Rep. 2022 Feb 22;38(8):110408. doi: 10.1016/j.celrep.2022.110408.
The adipose tissue is a key site regulating energy metabolism. One of the contributing factors behind this is browning of white adipose tissue (WAT). However, knowledge of the intracellular determinants of the browning process remains incomplete. By generating adipocyte-specific Senp2 knockout (Senp2-aKO) mice, here we show that SENP2 negatively regulates browning by de-conjugating small ubiquitin-like modifiers from C/EBPβ. Senp2-aKO mice are resistant to diet-induced obesity due to increased energy expenditure and heat production. Senp2 knockout promotes beige adipocyte accumulation in inguinal WAT by upregulation of thermogenic gene expression. In addition, SENP2 knockdown promotes thermogenic adipocyte differentiation of precursor cells isolated from inguinal and epididymal WATs. Mechanistically, sumoylated C/EBPβ, a target of SENP2, suppresses expression of HOXC10, a browning inhibitor, by recruiting a transcriptional repressor DAXX. These findings indicate that a SENP2-C/EBPβ-HOXC10 axis operates for the control of beige adipogenesis in inguinal WAT.
脂肪组织是调节能量代谢的关键部位。导致这种情况的一个因素是白色脂肪组织（WAT）的褐色化。然而，褐色化过程的细胞内决定因素的知识仍然不完整。通过生成脂肪细胞特异性的 Senp2 敲除（Senp2-aKO）小鼠，我们发现 SENP2 通过从 C/EBPβ 上去除小泛素样修饰物来负调控褐色化。由于能量消耗和产热增加，Senp2-aKO 小鼠对饮食诱导的肥胖具有抗性。Senp2 敲除通过上调产热基因表达促进腹股沟 WAT 中的米色脂肪细胞积累。此外，SENP2 敲低促进了从腹股沟和附睾 WAT 分离的前体细胞的产热脂肪细胞分化。从机制上讲，SENP2 的靶标 SUMOylated C/EBPβ 通过募集转录抑制因子 DAXX 来抑制褐色化抑制剂 HOXC10 的表达。这些发现表明，SENP2-C/EBPβ-HOXC10 轴在控制腹股沟 WAT 中的米色脂肪生成中起作用。
