M2 macrophages independently promote beige adipogenesis via blocking adipocyte Ets1

Suyang Wu, Chen Qiu, Jiahao Ni, Wenli Guo, Jiyuan Song, Xingyin Yang, Yulin Sun, Yanjun Chen, Yunxia Zhu, Xiaoai Chang, Peng Sun, Chunxia Wang, Kai Li () and Xiao Han ()
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Suyang Wu: Nanjing Medical University
Chen Qiu: Nanjing Medical University
Jiahao Ni: Nanjing Medical University
Wenli Guo: Nanjing Medical University
Jiyuan Song: Nanjing Medical University
Xingyin Yang: Nanjing Medical University
Yulin Sun: Nanjing Medical University
Yanjun Chen: Nanjing Medical University
Yunxia Zhu: Nanjing Medical University
Xiaoai Chang: Nanjing Medical University
Peng Sun: Nanjing Medical University
Chunxia Wang: Shanghai Jiao Tong University School of Medicine
Kai Li: Nanjing Medical University
Xiao Han: Nanjing Medical University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Adipose tissue macrophages can promote beige adipose thermogenesis by altering local sympathetic activity. Here, we perform sympathectomy in mice and further eradicate subcutaneous adipose macrophages and discover that these macrophages have a direct beige-promoting function that is independent of sympathetic system. We further identify adipocyte Ets1 as a vital mediator in this process. The anti-inflammatory M2 macrophages suppress Ets1 expression in adipocytes, transcriptionally activate mitochondrial biogenesis, as well as suppress mitochondrial clearance, thereby increasing the mitochondrial numbers and promoting the beiging process. Male adipocyte Ets1 knock-in mice are completely cold intolerant, whereas male mice lacking Ets1 in adipocytes show enhanced energy expenditure and are resistant to metabolic disorders caused by high-fat-diet. Our findings elucidate a direct communication between M2 macrophages and adipocytes, and uncover a function for Ets1 in responding to macrophages and negatively governing mitochondrial content and beige adipocyte formation.

Date: 2024
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DOI: 10.1038/s41467-024-45899-4

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