Kinin B-1 receptor acts in adipose tissue to control fat distribution in a cell-nonautonomous manner

The kinin B-1 receptor (B1R) plays a role in inflammatory and metabolic processes. B1R deletion (B-1(-/-)) protects mice from diet-induced obesity and improves insulin and leptin sensitivity. In contrast, genetic reconstitution of B1R exclusively in adipose tissue reverses the lean phenotype of B-1(-/-) mice. To study the cell-nonautonomous nature of these effects, we transplanted epididymal white adipose tissue (eWAT) from wild-type donors (B-1(+/+)) into B-1(-/-) mice (B-1(+/+)-> B-1(-/-)) and compared them with autologous controls (B-1(+/+)-> B-1(+/+) or B-1(-/-)-> B-1(-/-)). We then fed these mice a high-fat diet for 16 weeks and investigated their metabolic phenotypes. B-1(+/+)-> B-1(-/-) mice became obese but not glucose intolerant or insulin resistant, unlike B-1(-/-)-> B-1(-/-) mice. Moreover, the endogenous adipose tissue of B-1(+/+)-> B-1(-/-) mice exhibited higher expression of adipocyte markers (e.g., Fabp4 and Adipoq) and changes in the immune cell pool. These mice also developed fatty liver. Wild-type eWAT transplanted into B-1(-/-) mice normalized circulating insulin, leptin, and epidermal growth factor levels. In conclusion, we demonstrated that B1R in adipose tissue controls the response to diet-induced obesity by promoting adipose tissue expansion and hepatic lipid accumulation in cell-nonautonomous manners.68816141623COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPSem informação2010/50526-0; 2014/27198-8; 2017/07975-8; 2017/01184-