CX3CR1hi macrophages sustain metabolic adaptation by relieving adipose-derived stem cell senescence in visceral adipose tissue
Zixin Zhou,
Huiying Zhang,
Yan Tao,
Haipeng Jie,
Jingyuan Zhao,
Jinhao Zang,
Huijie Li,
Yalin Wang,
Tianci Wang,
Hui Zhao,
Yuan Li,
Chun Guo,
Faliang Zhu,
Haiting Mao,
Lining Zhang,
Fengming Liu,
Qun Wang
Affiliations
Zixin Zhou
Key Laboratory of Infection and Immunity of Shandong Province, Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Huiying Zhang
Key Laboratory of Infection and Immunity of Shandong Province, Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Yan Tao
Key Laboratory of Infection and Immunity of Shandong Province, Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Haipeng Jie
Key Laboratory of Infection and Immunity of Shandong Province, Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China; Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Jingyuan Zhao
Key Laboratory of Infection and Immunity of Shandong Province, Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Jinhao Zang
Key Laboratory of Infection and Immunity of Shandong Province, Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Huijie Li
Key Laboratory of Infection and Immunity of Shandong Province, Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Yalin Wang
Key Laboratory of Infection and Immunity of Shandong Province, Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Tianci Wang
Key Laboratory of Infection and Immunity of Shandong Province, Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Hui Zhao
Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, China
Yuan Li
Key Laboratory of Infection and Immunity of Shandong Province, Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China; Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Chun Guo
Key Laboratory of Infection and Immunity of Shandong Province, Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Faliang Zhu
Key Laboratory of Infection and Immunity of Shandong Province, Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Haiting Mao
Department of Clinical Laboratory, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, China
Lining Zhang
Key Laboratory of Infection and Immunity of Shandong Province, Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Fengming Liu
Key Laboratory of Infection and Immunity of Shandong Province, Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Qun Wang
Key Laboratory of Infection and Immunity of Shandong Province, Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China; Corresponding author
Summary: Adipose-derived stem cells (ASCs) drive healthy visceral adipose tissue (VAT) expansion via adipocyte hyperplasia. Obesity induces ASC senescence that causes VAT dysfunction and metabolic disorders. It is challenging to restrain this process by biological intervention, as mechanisms of controlling VAT ASC senescence remain unclear. We demonstrate that a population of CX3CR1hi macrophages is maintained in mouse VAT during short-term energy surplus, which sustains ASCs by restraining their senescence, driving adaptive VAT expansion and metabolic health. Long-term overnutrition induces diminishment of CX3CR1hi macrophages in mouse VAT accompanied by ASC senescence and exhaustion, while transferring CX3CR1hi macrophages restores ASC reservoir and triggers VAT beiging to alleviate the metabolic maladaptation. Mechanistically, visceral ASCs attract macrophages via MCP-1 and shape their CX3CR1hi phenotype via exosomes; these macrophages relieve ASC senescence by promoting the arginase1-eIF5A hypusination axis. These findings identify VAT CX3CR1hi macrophages as ASC supporters and unravel their therapeutic potential for metabolic maladaptation to obesity.
