title: Divergent roles for adiponectin receptor 1 (AdipoR1) and AdipoR2 in mediating revascularization and metabolic dysfunction in vivo.
abstract: Adiponectin is a well described anti-inflammatory adipokine that is highly abundant in serum. Previous reports have found that adiponectin deficiency promotes cardiovascular and metabolic dysfunction in murine models, whereas its overexpression is protective. Two candidate adiponectin receptors, AdipoR1 and AdipoR2, are uncharacterized with regard to cardiovascular tissue homeostasis, and their in vivo metabolic functions remain controversial. Here we subjected AdipoR1- and AdipoR2-deficient mice to chronic hind limb ischemic surgery. 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. In view of this divergent receptor function in the hind limb ischemia model, AdipoR1- and AdipoR2-deficient mice were also evaluated in a model of diet-induced obesity. Strikingly, AdipoR1-deficient mice developed severe metabolic dysfunction compared with wild type, whereas AdipoR2-deficient mice were protected from diet-induced weight gain and metabolic perturbations. These data show that AdipoR2, but not AdipoR1, is functionally important in an in vivo model of ischemia-induced revascularization and that its expression is essential for the revascularization actions of adiponectin. These data also show that, in contrast to revascularization responses, AdipoR1, but not AdipoR2 deficiency, leads to diet-induced metabolic dysfunction, revealing that these receptors have highly divergent roles in vascular and metabolic homeostasis.
authors.affiliation: From the Whitaker Cardiovascular Institute, Department of Pharmacology and Experimental Therapeutics and.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Parker-Duffen
authors.affiliation: From the Whitaker Cardiovascular Institute.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: From the Whitaker Cardiovascular Institute.
authors.forename: Marcy
authors.initials: M
authors.lastname: Silver
authors.affiliation: From the Whitaker Cardiovascular Institute.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Zuriaga
authors.affiliation: From the Whitaker Cardiovascular Institute.
authors.forename: Susan
authors.initials: S
authors.lastname: MacLauchlan
authors.affiliation: From the Whitaker Cardiovascular Institute, Department of Medicine-Renal Section, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Tamar R
authors.initials: TR
authors.lastname: Aprahamian
authors.affiliation: From the Whitaker Cardiovascular Institute, Department of Pharmacology and Experimental Therapeutics and kxwalsh@bu.edu.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Walsh
mesh_terms: D000818:Animals; D005121:Extremities / Q000098:blood supply; D008659:Metabolic Diseases / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D054419:Receptors, Adiponectin / Q000502:physiology*
chemical_list: D054419:Receptors, Adiponectin; C475419:adiponectin receptor 1, mouse; C475421:adiponectin receptor 2, mouse
keywords: AdipoR1; AdipoR2; Adiponectin; Angiogenesis; Metabolism; Receptor; Vascular Biology
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