中南大学罗湘杭小组开发出皮肤-下丘脑轴与热应激和代谢功能障碍有关。2026年4月21日出版的《细胞》发表了这项成果。

课题组报道，暴露于热应激的小鼠在随后暴露于致肥性饮食后更容易发生代谢功能障碍。在热应激时，该研究团队发现皮肤源性钾化钾素相关肽酶14 （KLK14）升高，印记下丘脑LRRC7⁺星形胶质细胞。这些星形胶质细胞通过alkB同源物1、组蛋白H2A双加氧酶（ALKBH1）介导的γ-氨基丁酸（GABA）合成的表观遗传修饰进一步抑制邻近室旁核细胞（PVN）^OXT神经元的活性，以交感神经系统依赖的方式驱动内脏脂肪沉积。热应激暴露也增加了人类受试者对代谢功能障碍的易感性，维生素A治疗限制了KLK14的产生，并改善了人类和小鼠的代谢紊乱。总之，他们的发现揭示了皮肤-下丘脑轴将热记忆和代谢功能障碍联系起来，并强调了全球变暖正在加剧代谢疾病。

据介绍，随着全球气温的持续上升，与热应激相关的慢性健康疾病的患病率有所增加。然而，热应激是否对代谢健康有持久的影响尚不清楚。

附：英文原文

Title: A skin-hypothalamus axis couples heat stress and metabolic dysfunction

Author: Hai-Yan Zhou, Xu Feng, Jie Wen, Yao Xiao, Li-Wen Wang, Lin-Yun Chen, Gen-Qing Xie, Jia-Jun Zhao, Yan Huang, Xiang-Hang Luo

Issue&Volume: 2026-04-21

Abstract: With the ongoing rise in global temperatures, the prevalence of heat-stress-related chronic health disorders has increased. However, whether heat stress has an enduring impact on metabolic health remains unclear. Here, we report that mice exposed to heat stress were more susceptible to metabolic dysfunction upon subsequent exposure to an obesogenic diet. Upon heat stress, we found that elevated skin-derived kallikrein-related peptidase 14 (KLK14) imprinted hypothalamic LRRC7+ astrocytes. These astrocytes further suppressed neighboring paraventricular nucleus (PVN)OXT neuron activity via alkB homolog 1, histone H2A dioxygenase (ALKBH1)-mediated epigenetic modification of γ-aminobutyric acid (GABA) synthesis, thus driving visceral fat deposition in a sympathetic nervous-system-dependent manner. Heat stress exposure also increased susceptibility to metabolic dysfunction in human subjects, with vitamin A treatment limiting the production of KLK14 and ameliorating metabolic disturbances in humans and mice. Together, our findings reveal a skin-hypothalamus axis linking heat memory and metabolic dysfunction and highlight that global warming is exacerbating metabolic diseases.

DOI: 10.1016/j.cell.2026.03.045

Source: https://www.cell.com/cell/abstract/S0092-8674(26)00346-6