Sex‐specific characterization of aortic function and inflammation in a new diet‐induced mouse model of metabolic syndrome

Perivascular adipose tissue (PVAT) expansion promotes inflammation and vascular dysfunction in metabolic syndrome (MetS), but the sexual dimorphisms of PVAT are poorly understood. Using a new mouse model of diet-induced MetS, we characterized the aorta and determined the influence of PVAT on vascular function in males and females. Six-week-old C57BL/6 mice were fed either a high-fat diet (43% kcal in food) with high sugar and salt in their drinking water (10% high fructose corn syrup and 0.9% NaCl; HFSS), or a normal chow diet (NCD) for 10 weeks. The aorta was characterized at endpoint using pin myography, flow cytometry, bulk RNA-sequencing, GSEA analysis, and histology. Compared to NCD-fed mice, HFSS-fed mice displayed higher weight gain, fasting blood glucose, systolic blood pressure, aortic fibrosis, and perivascular adipocyte cross-sectional area, regardless of sex (p < .05). Circulating adiponectin levels were also higher in HFSS-fed males compared to NCD males. PVAT enhanced U46619-mediated contraction in HFSS males only. HFSS increased the expression of immune regulation genes in female PVAT and ion transport genes in male PVAT but had no effect on total numbers of immune cells in the aorta in either sex. Despite having similar effects on metabolic parameters in males and females, HFSS caused contrasting effects on vascular function with and without PVAT. These data highlight the sexual dimorphisms of PVAT in regulating the vasculature in healthy and diseased states.