The Involvement of Sirtuin 1 Dysfunction in High-Fat Diet-Induced Vascular Dysfunction in Mice

Autor: Ning Xia, Gisela Reifenberg, Christian Schirra, Huige Li
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Antioxidants, Vol 11, Iss 3, p 541 (2022)
Druh dokumentu: article
ISSN: 2076-3921
DOI: 10.3390/antiox11030541
Popis: High-fat diet (HFD)-induced vascular impairment in mice is associated with a dysfunction of the perivascular adipose tissue (PVAT). The present study was conducted to investigate the involvement of sirtuin 1 (SIRT1). Male C57BL/6J mice were fed an HFD for 20 weeks to induce obesity. Vascular function was analyzed using a wire myograph system. In obese mice, the vasodilator response of PVAT-containing aortas to acetylcholine was reduced, although the vascular function of PVAT-free aortas remained normal. SIRT1 activity in PVAT of obese mice was reduced despite enhanced SIRT1 expression. Nicotinamide adenine dinucleotide (NAD+) levels and the NAD+/NADH ratio in the PVAT of obese mice were decreased, which was likely attributable to a downregulation of the NAD+-producing enzyme NAMPT. The reduced SIRT1 activity was associated with an enhanced acetylation of the endothelial nitric oxide synthase (eNOS) in the PVAT. Ex vivo incubation of PVAT-containing aorta from obese mice with NAD+ led to a complete normalization of vascular function. Thus, reduced SIRT1 activity due to NAD+ deficiency is involved in obesity-induced PVAT dysfunction.
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