Divergent Roles for Adiponectin Receptor 1 (AdipoR1) and AdipoR2 in Mediating Revascularization and Metabolic Dysfunction in Vivo

Abstract

Background: Adiponectin has vascular and metabolic protective actions; however, its in vivo receptor-mediated signaling pathways are incompletely understood. Results: Adiponectin receptor 1 (AdipoR1)-deficiency exacerbates diet-induced metabolic dysfunction, and AdipoR2 deficiency results in impaired revascularization.

High fat diet induced changes in gastric vagal afferent response to adiponectin

“…However some insight can be gained from examining the phenotypes of adiponectin receptor knockout mice. ADIPOR1 knockout mice have increased body weight, whereas, ADIPOR2 knockout mice have decreased body weight compared to controls [57]. If we speculate that the knockout phenotype is due, at least in part, to disruption of adiponectin effects on GVAs then ADIPOR2 is likely the receptor subtype which adiponectin activates on GVAs.…”

Obesity-Induced Changes in Adipose Tissue Microenvironment and Their Impact on Cardiovascular Disease

“…Early, it was reported that the beneficial actions of adiponectin on metabolic function and AMPK signaling pathway is mediated through combined signaling through its cell surface receptors AdipoR1 and AdipoR2 304 . However, subsequent studies suggest that AdipoR1 and AdipoR2 have opposing actions: AdipoR1-deficiency in mice leads to metabolic dysfunction, whereas AdipoR2-deficiency actually promotes resistance to obesity and insulin resistance 305–307 . The roles of AdipoR1 and AdipoR2 in CV tissues have mostly been deduced from cell culture studies.…”

Review: adiponectin in retinopathy

“…In type 2 diabetes, AdipoRon administration improves insulin resistance and glucose intolerance in obese mice[81], providing a promising therapeutic approach for the treatment of diabetes and diabetes-related complications. However, some studies also suggest that AdipoR1 and AdipoR2 have divergent roles in mediating vascular signaling and energy metabolism[99]. AdipoR2, but not AdipoR1, improves ischemia-induced vascular changes[99].…”

“…However, some studies also suggest that AdipoR1 and AdipoR2 have divergent roles in mediating vascular signaling and energy metabolism[99]. AdipoR2, but not AdipoR1, improves ischemia-induced vascular changes[99]. AdipoR1-deficient mice are vulnerable to high-fat diet-induced obesity with increased adiposity, decreased glucose tolerance and spontaneous locomotor activity, while adipoR2-deficient mice are resistant to these metabolic dysfunctions[99, 100].…”

“…AdipoR2, but not AdipoR1, improves ischemia-induced vascular changes[99]. AdipoR1-deficient mice are vulnerable to high-fat diet-induced obesity with increased adiposity, decreased glucose tolerance and spontaneous locomotor activity, while adipoR2-deficient mice are resistant to these metabolic dysfunctions[99, 100]. Therefore, further understanding of the functions of each APN receptor and the chemical synthesis of more specific receptor agonists might be helpful to optimize clinical application.…”