Adiponectin directly improves endothelial dysfunction in obese rats through the AMPK-eNOS Pathway.
OBJECTIVE
Hypoadiponectinemia has been proved to be closely related to endothelial dysfunction in peripheral arteries and is thought to be an independent risk factor for cardiovascular disease. The objective of this study was to investigate whether adiponectin might independently improve endothelial dysfunction in aorta isolated from high-fat-diet-induced obese. Sprague-Dawley rat and to study the mechanism involved.


METHODS
Male Sprague-Dawley rats were fed with a regular or a high-fat diet for 6 weeks. The aorta was isolated, and vascular segments were incubated with vehicle or the globular adiponectin (globular domain (gAD); 2 mg ml(-1)) for 2 h. The effect of gAD on endothelial function and nitric oxide (NO) production was determined. Human aortic endothelial cells in primary culture were treated with vehicle or gAD (4 mg ml(-1)). The effect of gAD on the level of phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser1177, AMPK at Thr176 and Akt at Ser473 in endothelial cells were determined.


RESULTS
Severe endothelial dysfunction was observed in high-fat diet fed rat aortic segments. After gAd incubation, the endothelium-dependent relaxation was partly improved and total production of nitric oxide as result of enhanced eNOS activity was also increased. In the cultured endothelial cell line HUVEC, globular adiponectin increased the activity of eNOS through activating AMPK by stimulating its phosphorylation at Thr176 but not Akt.


CONCLUSIONS
The demonstration in the current study that adiponectin reverses endothelial dysfunction through increasing NO production by eNOS phosphorylation, and decreasing NO inactivation by blocking superoxide production provides a new direction in the prevention of vascular injury in the obesity population.
Deng
G
G
Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China.
Long
Y
Y
Yu
Y-R
YR
Li
M-R
MR
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D052242:Adiponectin / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D004041:Dietary Fats / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D052242:Adiponectin; D004041:Dietary Fats; D052250:Nitric Oxide Synthase Type III; D055372:AMP-Activated Protein Kinases