Kinin B1 Receptor Acts in Adipose Tissue to Control Fat Distribution in a Cell-Nonautonomous Manner

Abstract

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., <i>Fabp4</i> and <i>Adipoq</i>) 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.