Female Dahl salt sensitive (DSS) rats on a high‐fat diet have greater increases in adiposity and blood pressure relative to males
Authors: Snyder Elizabeth Caroline , Ramirez Lindsey , Sullivan Jennifer 
Published: April 2020

BackgroundYoung women are typically resistant to cardiovascular disease (CVD) relative to age‐matched men. Previous basic science and epidemiological studies suggest that this protection is compromised by chronic consumption of a diet high in saturated fat through mechanisms that are poorly understood. The current study tests the hypothesis that female rats fed a diet rich in saturated fat will be more susceptible to adipose accumulation and increases in blood pressure (BP) than age‐matched male rats.MethodsMale and female DSS rats were randomized into groups fed either a high‐fat diet (HFD, 60% calories by fat) or a normal‐fat control diet (NFD, 16% calories by fat) at 5 weeks of age. Body weights were measured weekly and body fat composition was measured by nuclear magnetic resonance (NMR) at 7, 10, and 15 weeks of age. Mean arterial BP was measured by telemetry from 9 weeks of age to the end of the study at 15 weeks. After 10 weeks of dietary treatment (15 weeks of age), rats were euthanized. Gonadal fat pads were isolated, weighed and fixed to measure the diameter of adipocytes.ResultsAll rats gained weight over the 10‐week treatment period and weight gain was comparable between HFD and NFD groups of both sexes (Pdiet=0.85; Pinteraction=0.64). Male rats were heavier than female rats at all time points (Psex<0.0001). Despite comparable increase in weight, 10 weeks of HFD resulted in greater body fat mass versus NFD in both sexes (Pdiet=0.05). There were no differences in percent fat mass between the sexes (Psex=0.52; Pinteraction=0.70). However, when percent increase in body fat was calculated, HFD resulted in greater increases in fat gain over the course of treatment than NFD (Pdiet=0.01), and females (41±8% on NFD vs 102±2% on HFD) exhibited a greater increase than males (52±7% on NFD vs 60±14% on HFD; Psex=0.2; Pinteraction=0.03). BP was greater in both male and female rats on HFD vs. NFD at 9 weeks of age (after 4 weeks of treatment: male NFD, 123±0.96 mmHg; male HFD, 131±0.44 mmHg; female NFD, 123±0.47 mmHg; female HFD, 131±0.54 mmHg) and BP was comparable between the sexes (Pdiet=0.0002; Psex=0.49; Pinteraction=0.76). HFD resulted in further increases in BP in both sexes compared with rats treated with NFD (Pdiet=0.0014). After 10 weeks of dietary treatment, females on HFD demonstrated a greater increase in BP than males (Psex=0.0618; Pinteraction=0.049; male HFD, 145±0.61 mmHg; female HFD, 166±1.05 mmHg). At the end of the treatment, gonadal fat pads were isolated and weighed. Rats fed a HFD had larger gonadal fat pads than rats on NFD (Pdiet<0.0001), and females had heavier fat pads than males (Psex=0.0026; Pinteraction=0.79). Heavier fat pad weight, however, was not associated with larger adipocyte size. Adipocyte diameter was increased in HFD rats vs. NFD (Pdiet<0.0001), however the increase was comparable between the sexes (Psex=0.01; Pinteraction=0.2).DiscussionIn conclusion, female DSS rats demonstrate enhanced susceptibility to adipose accumulation relative to males in the absence of overt obesity. Moreover, greater increases in adiposity in females were accompanied by greater increases in BP compared with males. Future experiments will examine the mechanisms by which a more mal‐adaptive adipose tissue phenotype exacerbates CVD risk in females.