title: Adiponectin is required for PPARγ-mediated improvement of endothelial function in diabetic mice.
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.
authors: 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.
authors: Wing Tak
authors: WT
authors: Wong
authors: Xiao Yu
authors: XY
authors: Tian
authors: Aimin
authors: A
authors: Xu
authors: Jun
authors: J
authors: Yu
authors: Chi Wai
authors: CW
authors: Lau
authors: Ruby L C
authors: RL
authors: Hoo
authors: Yu
authors: Y
authors: Wang
authors: Vivian W Y
authors: VW
authors: Lee
authors: Karen S L
authors: KS
authors: Lam
authors: Paul M
authors: PM
authors: Vanhoutte
authors: Yu
authors: Y
authors: Huang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D000077154:Rosiglitazone; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000627:therapeutic use
chemical_list: D052242:Adiponectin; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D009569:Nitric Oxide; D000242:Cyclic AMP; D052250:Nitric Oxide Synthase Type III; D017868:Cyclic AMP-Dependent Protein Kinases; D055372:AMP-Activated Protein Kinases