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; Bing Luan

doi:10.1038/s41467-022-30757-y

Targeting parvalbumin promotes M2 macrophage polarization and energy expenditure in mice

Nat Commun. 2022 Jun 8;13(1):3301. doi: 10.1038/s41467-022-30757-y.

Authors

Shaojian Lin^#^{1

2}, Anke Zhang^#³, Ling Yuan^#¹, Yufan Wang^#⁴, Chuan Zhang¹, Junkun Jiang¹, Houshi Xu⁵, Huiwen Yuan¹, Hui Yao¹, Qianying Zhang⁶, Yong Zhang⁶, Meiqing Lou⁵, Ping Wang⁷, Zhen-Ning Zhang⁸, Bing Luan⁹

Affiliations

¹ Department of Endocrinology, Tongji Hospital Affiliated to Tongji University, School of Medicine, Tongji University, Shanghai, China.
² Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
⁴ Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
⁵ Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁶ The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.
⁷ Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
⁸ Translational Medical Center for Stem Cell Therapy & Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.
⁹ Department of Endocrinology, Tongji Hospital Affiliated to Tongji University, School of Medicine, Tongji University, Shanghai, China. bluan@tongji.edu.cn.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue / metabolism
Animals
Diet, High-Fat
Energy Metabolism
Inflammation / metabolism
Macrophage Activation*
Macrophages
Mice
Mice, Inbred C57BL
Obesity / metabolism
Parvalbumins* / metabolism

Substances

Parvalbumins