Targeting parvalbumin promotes M2 macrophage polarization and energy expenditure in mice.

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. Exercise increases energy expenditure and suppresses obesity, but the effector mechanisms are not still unclear. Here the authors profile serum proteomics in exercised mice to find reduced parvalbumin levels that correlate with increased M2 macrophage and suppressed diet-induced obesity to hint parvalbumin as a potential therapy target against obesity. [ABSTRACT FROM AUTHOR]