Calycosin directly improves perivascular adipose tissue dysfunction by upregulating the adiponectin/AMPK/eNOS pathway...

Perivascular adipose tissue (PVAT) loses its anti-contractile activity in obesity. Calycosin, the major bioactive isoflavonoid, was shown to protect endothelial function. However, effects of calycosin on PVAT function in obesity remain unclear. We aimed to investigate the effects of calycosin on the anti-contractile activity of PVAT in obese mice and its potential mechanisms. Obesity in mice was induced with a high-fat diet, with or without calycosin treatment. Thoracic aorta responses to phenylephrine were determined. AMP protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) levels were analyzed by western blotting. Adiponectin, TNF-α levels and superoxide production were measured in the PVAT. Calycosin treatment significantly increased the anti-contractile response of PVAT, which was impaired in obese mice. This beneficial effect of calycosin was eliminated by treatments of blocking adiponectin, AMPK or eNOS. Similar results were observed for calycosin treatment ex vivo. Treatment of obese mice with calycosin significantly increased adiponectin levels, activated AMPK and eNOS phosphorylation and reduced superoxide production and TNF-α levels in PVAT. Our results indicated that calycosin restored PVAT induced anti-contractile activity and affected PVAT function through the adiponectin/AMPK/eNOS pathway in obese mice.