Perivascular adipose tissue from female rats fed a high-fat diet impaired mesenteric artery vasodilation.

High-fat diet (HFD) is a cardiovascular risk factor that may disproportionately affect women compared to men. HFD alters perivascular adipose tissue (PVAT), which surrounds arteries and regulates vascular function. This study investigated the sex-specific effects of HFD on PVAT-mediated vascular dysfunction. Male and female Sprague-Dawley rats were fed a normal chow diet (NCD) or HFD for 16 weeks. Thoracic aortic PVAT was isolated, and PVAT adipokine expression and inflammatory markers were measured. We then assessed PVAT-conditioned media effects on vasodilation, endothelial oxidative stress, and endothelial nitric oxide (NO) synthase. PVAT-conditioned media from HFD female but not male rats impaired acetylcholine-induced vasodilation in mesenteric arteries; however, it did not increase oxidative stress or decrease endothelial NO synthase activation in rat endothelial cells in vitro. PVAT from HFD female rats had higher CD68 expression and acetyl-NF-κB/NF-κB ratio than PVAT from NCD female rats. Overall, HFD caused a greater PVAT-induced impairment in vasodilation in female as compared to male rats, which aligns with the heightened cardiovascular risk in women consuming a HFD.