Rhein targets macrophage SIRT2 to promote adipose tissue thermogenesis in obesity in mice
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.
Authors
- Yingying Xue (ORCID: https://orcid.org/0000-0003-3103-5559)
- Lixuan Shen
- Wenbin Shang (ORCID: https://orcid.org/0000-0002-0317-5928)
- Yingying Xiang (ORCID: https://orcid.org/0000-0001-6960-6623)
- Xizhong Yu
- Penghua Fang (ORCID: https://orcid.org/0000-0002-8915-0616)
- Ping-Yuan Xu
- Yue Cao (ORCID: https://orcid.org/0000-0002-2356-4031)
- Juan Zhao (ORCID: https://orcid.org/0000-0002-8079-1572)
- Ruonan Zhou (ORCID: https://orcid.org/0000-0002-6861-9411)
- Ziwei Zhu (ORCID: https://orcid.org/0000-0002-6189-8796)
- Ziwei Wang (ORCID: https://orcid.org/0009-0003-8050-9121)
- Jing Yan (ORCID: https://orcid.org/0000-0003-2824-1431)
- Qin Yang (ORCID: https://orcid.org/0000-0003-3792-2116)
- Yu Jin (ORCID: https://orcid.org/0009-0002-6396-4889)
Institutions
- Nanjing University of Chinese Medicine (CN)
- University of California, Irvine (US)
- Jiangsu Province Hospital (CN)
Publication Details
- Journal
- Communications Biology
- Published
- 2024-08-16
- DOI
- https://doi.org/10.1038/s42003-024-06693-6
- Citations
- 10
- Primary Topic
- Adipose Tissue and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 3.27
Funders
- National Natural Science Foundation of China
- Government of Jiangsu Province
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Graduate Research and Innovation Projects of Jiangsu Province