C1q/ TNF ‐related protein 9 improves the anti‐contractile effects of perivascular adipose tissue via the AMPK ‐ eNOS pathway in diet‐induced obese mice

Summary The anti‐contractile property of perivascular adipose tissue ( PVAT ) is abolished through an endothelium‐dependent pathway in obesity. C1q/tumor necrosis factor‐related protein ( CTRP )9 improved endothelial function by promoting endothelium‐dependent vasodilatation. The aims of this study were to investigate whether CTRP 9 improves the anti‐contractile effect of PVAT and protects against PVAT dysfunction in obese mice. The mice were treated with a high‐fat diet with or without CTRP 9 treatment. Thoracic aortas with or without PVAT ( PVAT + or PVAT −) were prepared, and concentration‐dependent responses to phenylephrine were measured. Obese mice showed a significantly increased contractile response, which was suppressed by CTRP 9 treatment both with and without PVAT . PVAT significantly reduced the anti‐contractile effect in obese mice, which was partially restored by CTRP 9 treatment. Treatment of the aortic rings ( PVAT +) with inhibitors of AMP protein kinase ( AMPK ), Akt and endothelial nitric oxide synthase ( eNOS ) attenuated the beneficial effect of CTRP 9 on PVAT . Similar results were observed when we pretreated the aortic rings with CTRP 9 ex vivo. CTRP 9 significantly enhanced the phosphorylation levels of AMPK , Akt and eNOS , and reduced superoxide production and TNF ‐ α levels in PVAT from obese mice. Our study suggests that CTRP 9 enhanced the anti‐contractile effect of PVAT and improved PVAT function by activating the AMPK ‐ eNOS pathway in obese mice.