Adiponectin is required for PPARγ-mediated improvement of endothelial function in diabetic mice

Cell Metab. 2011 Jul 6;14(1):104-15. doi: 10.1016/j.cmet.2011.05.009.


Rosiglitazone is a PPARγ agonist commonly used to treat diabetes. In addition to improving insulin sensitivity, rosiglitazone restores normal vascular function by a mechanism that remains poorly understood. Here we show that adiponectin is required to mediate the PPARγ effect on vascular endothelium of diabetic mice. In db/db and diet-induced obese mice, PPARγ activation by rosiglitazone restores endothelium-dependent relaxation of aortae, whereas diabetic mice lacking adiponectin or treated with an anti-adiponectin antibody do not respond. Rosiglitazone stimulates adiponectin release from fat explants, and subcutaneous fat transplantation from rosiglitazone-treated mice recapitulates vasodilatation in untreated db/db recipients. Mechanistically, adiponectin activates AMPK/eNOS and cAMP/PKA signaling pathways in aortae, which increase NO bioavailability and reduce oxidative stress. Taken together, these results demonstrate that adipocyte-derived adiponectin is required for PPARγ-mediated improvement of endothelial function in diabetes. Thus, the adipose tissue represents a promising target for treating diabetic vasculopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Adiponectin / metabolism*
  • Animals
  • Aorta / metabolism
  • Aorta / physiology
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / physiology
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Mice
  • Mice, Obese
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • PPAR gamma / agonists
  • PPAR gamma / metabolism*
  • Rosiglitazone
  • Signal Transduction
  • Thiazolidinediones / therapeutic use


  • Adiponectin
  • Hypoglycemic Agents
  • PPAR gamma
  • Thiazolidinediones
  • Rosiglitazone
  • Nitric Oxide
  • Cyclic AMP
  • Nitric Oxide Synthase Type III
  • Cyclic AMP-Dependent Protein Kinases
  • AMP-Activated Protein Kinases