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

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

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1
Institute of Vascular Medicine, Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.

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.

PMID:
21723508
DOI:
10.1016/j.cmet.2011.05.009
[Indexed for MEDLINE]
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