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

Wing Tak Wong, Xiao Yu Tian, Aimin Xu, Jun Yu, Chi Wai Lau, Ruby L.C. Hoo, Yu Wang, Vivian W.Y. Lee, Karen S.L. Lam, Paul M. Vanhoutte, Yu Huang

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)104-115
Number of pages12
JournalCell Metabolism
Volume14
Issue number1
DOIs
StatePublished - Jul 6 2011

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Adiponectin is required for PPARγ-mediated improvement of endothelial function in diabetic mice'. Together they form a unique fingerprint.

Cite this