Targeting parvalbumin promotes M2 macrophage polarization and energy expenditure in mice

Shaojian Lin, Anke Zhang, Ling Yuan, Yufan Wang, Chuan Zhang, Junkun Jiang, Houshi Xu, Huiwen Yuan, Hui Yao, Qianying Zhang, Yong Zhang, Meiqing Lou, Ping Wang, Zhen-Ning Zhang and Bing Luan ()
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Shaojian Lin: Tongji Hospital Affiliated to Tongji University, School of Medicine, Tongji University
Anke Zhang: Second Affiliated Hospital, School of Medicine, Zhejiang University
Ling Yuan: Tongji Hospital Affiliated to Tongji University, School of Medicine, Tongji University
Yufan Wang: Shanghai General Hospital, Shanghai Jiao Tong University
Chuan Zhang: Tongji Hospital Affiliated to Tongji University, School of Medicine, Tongji University
Junkun Jiang: Tongji Hospital Affiliated to Tongji University, School of Medicine, Tongji University
Houshi Xu: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Huiwen Yuan: Tongji Hospital Affiliated to Tongji University, School of Medicine, Tongji University
Hui Yao: Tongji Hospital Affiliated to Tongji University, School of Medicine, Tongji University
Qianying Zhang: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College
Yong Zhang: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College
Meiqing Lou: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Ping Wang: Tongji University Cancer Center, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University
Zhen-Ning Zhang: Shanghai East Hospital, School of Life Sciences and Technology, Tongji University
Bing Luan: Tongji Hospital Affiliated to Tongji University, School of Medicine, Tongji University

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Exercise benefits M2 macrophage polarization, energy homeostasis and protects against obesity partially through exercise-induced circulating factors. Here, by unbiased quantitative proteomics on serum samples from sedentary and exercised mice, we identify parvalbumin as a circulating factor suppressed by exercise. Parvalbumin functions as a non-competitive CSF1R antagonist to inhibit M2 macrophage activation and energy expenditure in adipose tissue. More importantly, serum concentrations of parvalbumin positively correlate with obesity in mouse and human, while treating mice with a recombinant parvalbumin blocker prevents its interaction with CSF1R and promotes M2 macrophage polarization and ameliorates diet-induced obesity. Thus, although further studies are required to assess the significance of parvalbumin in mediating the effects of exercise, our results implicate parvalbumin as a potential therapeutic strategy against obesity in mice.

Date: 2022
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DOI: 10.1038/s41467-022-30757-y

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