Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China; Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA; Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Cell Rep. 2018 Jun 19;23(12):3607-3620. doi: 10.1016/j.celrep.2018.05.065.
Exposure to cold temperature is well known to upregulate heat shock protein (Hsp) expression and recruit and/or activate brown adipose tissue and beige adipocytes in humans and animals. However, whether and how Hsps regulate adipocyte function for energy homeostatic responses is poorly understood. Here, we demonstrate a critical role of Hsp20 as a negative regulator of adipocyte function. Deletion of Hsp20 enhances non-shivering thermogenesis and suppresses inflammatory responses, leading to improvement of glucose and lipid metabolism under both chow diet and high-fat diet conditions. Mechanistically, Hsp20 controls adipocyte function by interacting with the subunit of the ubiquitin ligase complex, F-box only protein 4 (FBXO4), and regulating the ubiquitin-dependent degradation of peroxisome proliferation activated receptor gamma (PPARγ). Indeed, Hsp20 deficiency mimics and enhances the pharmacological effects of the PPARγ agonist rosiglitazone. Together, our findings suggest a role of Hsp20 in mediating adipocyte function by linking β-adrenergic signaling to PPARγ activity.
暴露于低温环境中会导致热休克蛋白（Hsp）表达上调，并招募和/或激活人类和动物的棕色脂肪组织和米色脂肪细胞。然而，Hsp 是否以及如何调节脂肪细胞功能以进行能量稳态反应尚不清楚。在这里，我们证明了 Hsp20 作为脂肪细胞功能的负调节剂的关键作用。Hsp20 的缺失增强了非颤抖性产热，并抑制了炎症反应，从而在正常饮食和高脂肪饮食条件下改善了葡萄糖和脂质代谢。在机制上，Hsp20 通过与泛素连接酶复合物的亚单位 F-box 蛋白 4（FBXO4）相互作用来控制脂肪细胞功能，并调节过氧化物酶体增殖物激活受体 γ（PPARγ）的泛素依赖性降解。事实上，Hsp20 缺乏模拟并增强了 PPARγ 激动剂罗格列酮的药理作用。总之，我们的研究结果表明，Hsp20 通过将β-肾上腺素能信号与 PPARγ 活性联系起来，在调节脂肪细胞功能方面发挥作用。
