# Perivascular adipose tissue from female rats fed a high‐fat diet impaired mesenteric artery vasodilation

## TL;DR

A high-fat diet harms blood vessel function more in female rats than males, possibly explaining higher cardiovascular risks in women.

## Contribution

This study reveals sex-specific effects of high-fat diets on perivascular adipose tissue-induced vascular dysfunction.

## Key findings

- PVAT from HFD-fed female rats impaired mesenteric artery vasodilation more than in males.
- HFD female PVAT showed increased CD68 and acetyl-NF-κB/NF-κB ratio compared to controls.
- HFD female PVAT did not increase oxidative stress or reduce NO synthase activation in vitro.

## Abstract

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.