Kinin B 1 Receptor Acts in Adipose Tissue to Control Fat Distribution in a Cell-Nonautonomous Manner

The kinin B receptor (B R) plays a role in inflammatory and metabolic processes. B R deletion (B ) protects mice from diet-induced obesity and improves insulin and leptin sensitivity. In contrast, genetic reconstitution of B R exclusively in adipose tissue reverses the lean phenotype of B mice. To study the cell-nonautonomous nature of these effects, we transplanted epididymal white adipose tissue (eWAT) from wild-type donors (B ) into B mice (B →B ) and compared them with autologous controls (B →B or B →B ). We then fed these mice a high-fat diet for 16 weeks and investigated their metabolic phenotypes. B →B mice became obese but not glucose intolerant or insulin resistant, unlike B →B mice. Moreover, the endogenous adipose tissue of B →B mice exhibited higher expression of adipocyte markers (e.g., and ) and changes in the immune cell pool. These mice also developed fatty liver. Wild-type eWAT transplanted into B mice normalized circulating insulin, leptin, and epidermal growth factor levels. In conclusion, we demonstrated that B R in adipose tissue controls the response to diet-induced obesity by promoting adipose tissue expansion and hepatic lipid accumulation in cell-nonautonomous manners.