2. Academic Validation
  3. Rhein targets macrophage SIRT2 to promote adipose tissue thermogenesis in obesity in mice

Rhein targets macrophage SIRT2 to promote adipose tissue thermogenesis in obesity in mice

  • Commun Biol. 2024 Aug 16;7(1):1003. doi: 10.1038/s42003-024-06693-6.
Ruo-Nan Zhou 1 2,  Zi-Wei Zhu 1 2,  Ping-Yuan Xu 1 2,  Li-Xuan Shen 1 2,  Ziwei Wang 1 2,  Ying-Ying Xue 1 2,  Ying-Ying Xiang 1 2,  Yue Cao 1 2,  Xi-Zhong Yu 2,  Juan Zhao 2,  Yu Jin 2,  Jing Yan 2,  Qin Yang 3,  Peng-Hua Fang 4,  Wen-Bin Shang 5 6
Affiliations

Affiliations

  • 1 Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China.
  • 2 Key Laboratory for Metabolic Diseases in Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
  • 3 Department of Medicine, Physiology and Biophysics, University of California, Irvine, CA, 92697, USA.
  • 4 Key Laboratory for Metabolic Diseases in Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China. fphlcollegesci@njucm.edu.cn.
  • 5 Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China. wbshang@njucm.edu.cn.
  • 6 Key Laboratory for Metabolic Diseases in Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China. wbshang@njucm.edu.cn.
PMID: 39152196 DOI: 10.1038/s42003-024-06693-6
Abstract

Rhein, a component derived from rhubarb, has been proven to possess anti-inflammatory properties. Here, we show that rhein mitigates obesity by promoting adipose tissue thermogenesis in diet-induced obese mice. We construct a macrophage-adipocyte co-culture system and demonstrate that rhein promotes adipocyte thermogenesis through inhibiting NLRP3 inflammasome activation in macrophages. Moreover, clues from acetylome analysis identify SIRT2 as a potential drug target of rhein. We further verify that rhein directly interacts with SIRT2 and inhibits NLRP3 inflammasome activation in a SIRT2-dependent way. Myeloid knockdown of SIRT2 abrogates adipose tissue thermogenesis and metabolic benefits in obese mice induced by rhein. Together, our findings elucidate that rhein inhibits NLRP3 inflammasome activation in macrophages by regulating SIRT2, and thus promotes white adipose tissue thermogenesis during obesity. These findings uncover the molecular mechanism underlying the anti-inflammatory and anti-obesity effects of rhein, and suggest that rhein may become a potential drug for treating obesity.

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