Abstract

Diets high in saturated fats are increasingly linked to the development of hypertension, yet the mechanisms by which high saturated fat diet (HFD) increases blood pressure remain unclear. Although young women are typically protected from hypertension relative to age-matched men, recent studies suggest that the cardiovascular protection in young women is compromised by chronic consumption of a HFD. We hypothesize that chronic HFD treatment causes a greater increase in blood pressure in females via sex-specific activation and recruitment of T cells and adipocyte expansion. Male and female Dahl rats (n=4-5) were placed on HFD at 8 wks of age. After 4 wks of HFD, blood pressure (BP) significantly increased in male and female Dahl rats to a comparable degree. Although BP continued to increase over the course of 10 wks of HFD treatment, female rats have a greater increases in BP (~40 mmHg increase in BP) after 10 weeks of HFD vs. males (~20 mmHg increase in BP). Fat pad weight and adipose tissue expansion increased in WT rats of both sexes following 10 wks of HFD treatment, yet females exhibited greater increases in fat pad weight and adipose tissue expansion vs. males. To determine whether T cells contributes to sex differences in BP elevation in Dahl rats fed HFD, we utilized Dahl rats lacking CD247 which encodes the T cell receptor CD3 chain that is required for T cell signaling. 10 wks of HF feeding did not change BP in either sex of Dahl CD247 KO rats. There were attenuated increases in fat pad weight and adipocyte expansion in Dahl CD247 KO rats and females exhibited more pronounced attenuations than males. Flow cytometric analysis revealed that HFD decreased Tregs and increased Th17 cells in both sexes of Dahl WT rats and females on HFD had the most pro-inflammatory T cell profile indicted by the Th17 cells:Tregs ratio. Our data suggest that greater adipocyte expansion with a HFD feeding in female Dahl rats vs. male might result in greater recruitment and activation of pro-inflammatory T cells and larger increases in BP.

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