Adiponectin directly improves endothelial dysfunction in obese rats through the AMPK–eNOS Pathway

Abstract

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. SpragueDawley rat and to study the mechanism involved. Research Design and Subjects: 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 À1 ) 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 À1 ). 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. Conclusion: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.

Could a high-fat diet rich in unsaturated fatty acids impair the cardiovascular system?

“…In contrast to our results, some studies (50,51) have shown a decrease in endothelium-dependent vasorelaxation and no alteration in the maximal contractile responses to PE in renal arteries from saturated and unsaturated fatty acid-fed rats, compared with control rats, but there was no marked difference between them (50). These authors used a 34.4% unsaturated fatty acid diet over a 24-week period, while our study used an 83% unsaturated fatty acid diet over a 19-week period.…”

AMP-dependent Kinase Inhibits Oxidative Stress-induced Caveolin-1 Phosphorylation and Endocytosis by Suppressing the Dissociation between c-Abl and Prdx1 Proteins in Endothelial Cells

“…Ceolotto et al (41) reported that AMPK protects HUVEC against glucose-induced oxidative stress by suppressing hyperactivity of NAD(P)H oxidase. Deng et al (42) reported that AMPK protects human aortic endothelium by increasing NO production via endothelial NOS phosphorylation. In contrast to these studies, the present study revealed that AMPK protects the endothelium by inhibiting the dissociation between c-Abl and Prdx1.…”

Serum High Molecular Weight Adiponectin is Associated with Mild Renal Dysfunction in Japanese Adults

“…Moreover, adiponectin also has a direct effect on the vascular system to exert vasodilator actions, and increased blood flow. Adiponectin increases NO production through two mechanisms, namely, by activation of endothelial nitric oxide synthase (eNOS) enzyme activity and via an increase in eNOS expression in endothelial cells 37,38) . Thus, decreased adiponectin levels cause vascular dysfunction in the presence of inflammatory and oxidative vascular injuries, and enhance the predisposition to renal dysfunction.…”