Divergent roles for AdipoR1 and AdipoR2 in mediating revascularization and metabolic dysfunction (P6358)

Abstract

Abstract Adiponectin is a well-described anti-inflammatory adipokine with a collectin-like structure. Previous reports have found that its deficiency leads to cardiovascular and metabolic dysfunction whereas its overexpression is protective. Two adiponectin receptors, AdipoR1 and AdipoR2, are poorly characterized and their metabolic functions remain controversial. Here, we subjected AdipoR1- and AdipoR2-deficient mice to hind limb ischemia surgery, a mouse model of peripheral artery disease. Blood flow recovery in AdipoR1-deficient mice was similar to wild-type; however, revascularization in AdipoR2-deficient mice was severely attenuated. Treatment with adiponectin enhanced the recovery of wild-type mice but failed to rescue the impairment observed in AdipoR2-deficient mice. These data show for the first time that AdipoR2 is functionally important in an in vivo model of vascular disease and that its expression is essential for the revascularization actions of adiponectin. Given the connection between cardiovascular and metabolic disease, AdipoR1- and AdipoR2-deficient mice were also evaluated in a model of diet-induced obesity. Strikingly, AdipoR1-deficient mice developed severe metabolic dysfunction compared to wild-type littermates. In contrast, AdipoR2-deficient mice were protected from diet-induced weight gain and metabolic perturbations. Taken together, AdipoR1 and AdipoR2 have divergent roles in mouse models of vascular and metabolic disease.