脂肪因子IL-11/IL-11 Ra通过抑制鞘脂代谢来限制棕色脂肪细胞的产热能力
脂肪因子IL-11/IL-11Ra通过抑制鞘脂代谢来限制棕色脂肪细胞的产热能力
作者： 小柯机器人 发布时间：2026/5/15 20:31:13
本期文章：《细胞—代谢》：Online/在线发表
华中科技大学陈勇团队宣布他们的最新研究提出了脂肪因子IL-11/IL-11Ra通过抑制鞘脂代谢来限制棕色脂肪细胞的产热能力。相关论文于2026年5月14日发表于国际顶尖学术期刊《细胞—代谢》杂志上。
课题组发现白细胞介素(IL)-11是在肾上腺素能刺激下由脂肪细胞，尤其是棕色脂肪细胞诱导和分泌的。IL-11通过与IL-11受体α（IL-11Ra）结合抑制脂肪细胞产热，并作为维持能量稳态的“制动器”。脂肪细胞特异性IL-11Ra敲除小鼠在高脂肪饮食（HFD）下表现出全身能量消耗增加，葡萄糖和脂质代谢改善。抑制IL-11/IL-11Ra信号可以增强鞘氨醇激酶1 （Sphk1）驱动的鞘氨醇-1-磷酸（S1P）的产生，从而重塑棕色脂肪细胞内钙循环。值得注意的是，在肥胖小鼠中使用一种针对IL-11Ra的设计肽治疗可以有效减轻脂肪堆积和肥胖相关疾病。综上所述，他们的研究确定了棕色脂肪细胞衍生的IL-11在能量代谢中的生理和非规范机制，这可能是治疗肥胖的一个有希望的靶点。
据了解，脂肪细胞通过分泌促炎性细胞因子来应对能量过剩，从而表现出细胞可塑性。
附：英文原文
Title: Adipokine IL-11/IL-11Ra constrains sphingolipid metabolism to limit the thermogenic capacity of beige adipocytes
Author: Jiadai Liu, Ronghui Gao, Qianqian Kang, Zhihan Wang, Xuemin Peng, Jing Ge, Wenshe Wang, Hongyan Deng, Yuyu Xie, Zengzhe Zhu, Min Yang, Rui He, Huanyu Wang, Yulian Liu, Pema Maretich, Yongsheng Chang, Jichun Yang, Shingo Kajimura, Ruping Pan, Yong Chen
Issue&Volume: 2026-05-14
Abstract: Adipocytes exhibit cellular plasticity by secreting pro-inflammatory cytokines in response to an energy excess. Here, we identify that interleukin (IL)-11 is robustly induced and secreted from adipocytes, especially beige adipocytes upon adrenergic stimulation. IL-11 inhibits adipocyte thermogenesis through binding to IL-11 receptor a (IL-11Ra) and serves as a “brake” to maintain energy homeostasis. Adipocyte-specific IL-11Ra-knockout mice exhibit enhanced whole-body energy consumption and improved glucose and lipid metabolism under a high-fat diet (HFD). Inhibition of IL-11/IL-11Ra signaling enhances sphingosine kinase 1 (Sphk1)-driven production of sphingosine-1-phosphate (S1P), thus remodeling intracellular calcium cycling in beige adipocytes. Notably, treatment with a designed peptide against IL-11Ra in obese mice effectively alleviates fat accumulation and obesity-associated disorders. Taken together, our study defines a physiological and noncanonical mechanism of beige adipocyte-derived IL-11 in energy metabolism, which may serve as a promising target for the treatment of obesity.
DOI: 10.1016/j.cmet.2026.04.013
Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(26)00151-8