6533b834fe1ef96bd129d496

RESEARCH PRODUCT

Restoration of perivascular adipose tissue function in diet-induced obese mice without changing bodyweight

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Background and Purpose We have recently shown that a reduced function of endothelial nitric oxide synthase (eNOS) in the perivascular adipose tissue (PVAT) contributes crucially to obesity-induced vascular dysfunction in mice. The current study was conducted to test the hypothesis that vascular dysfunction in obesity can be reversed by in vivo improvement of PVAT eNOS activity. Experimental Approach Male C57BL/6 J mice were fed a high-fat diet (HFD) for 22 weeks to induce obesity. During the last 4 weeks of HFD feeding, the obese mice were treated orally with the standardized Crataegus extract WS® 1442 which has been shown previously to improve eNOS activity. Key Results Diet-induced obesity in mice markedly reduced the vasodilator response of thoracic aorta to acetylcholine in wire myograph experiments. Strikingly, this vascular dysfunction was only evident in PVAT-containing aorta but not in PVAT-free aorta. In vivo treatment of obese mice with WS® 1442 had no effect on body weight or epididymal fat mass, but completely restored the vascular function of PVAT-containing aorta. HFD feeding led to a reduced phosphorylation and an enhanced acetylation of PVAT eNOS, both effects were reversed by WS® 1442 treatment. Conclusion and Implication PVAT plays a key role in vascular dysfunction in diet-induced obese mice. Not obesity itself, but a PVAT dysfunction is responsible for the obesity-induced vascular disorders. Improving PVAT function by pharmacological means (e.g. with WS® 1442) can ameliorate vascular function even without reducing body weight or fat mass. This article is protected by copyright. All rights reserved.