The kinin B1 receptor (B1R) plays a role in inflammatory and metabolic processes. B1R deletion (B1−/−) 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 B1−/− mice. To study the cell-nonautonomous nature of these effects, we transplanted epididymal white adipose tissue (eWAT) from wild-type donors (B1+/+) into B1−/− mice (B1+/+→B1−/−) and compared them with autologous controls (B1+/+→B1+/+ or B1−/−→B1−/−). We then fed these mice a high-fat diet for 16 weeks and investigated their metabolic phenotypes. B1+/+→B1−/− mice became obese but not glucose intolerant or insulin resistant, unlike B1−/−→B1−/− mice. Moreover, the endogenous adipose tissue of B1+/+→B1−/− 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 B1−/− 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.
- Received October 23, 2018.
- Accepted May 28, 2019.
- © 2019 by the American Diabetes Association.