T Cells Contribute to Lipid Deposition in Male and Female Dahl Rats Fed a High Saturated Fat Diet

Abstract

BackgroundThe Dahl rat has been used as a model of high fat diet (HFD)‐induced hypertension and adiposity. Genetic deletion of T cells blunts HFD‐induced hypertension. However, it is not clear if deletion of T cells can also reduce the adiposity caused by the HFD. T cells have been shown to play a role in many inflammatory conditions which are characterized by dyslipidemia. Therefore, the goal of the current study was to test the hypothesis that deletion of T cells prevents lipid deposits in the liver and adipose tissue.Methods5‐week‐old male and female wildtype Dahl (WT; n=9‐19/group) or Dahl rats lacking T cells (CD247 knock out [KO] rats; n=3‐7/group) were randomized to either a control normal fat diet (NF; 7.2% calories from fat) or a high fat diet (HF; 36% calories from saturated fat) for 10 weeks. Following treatment, a subset of livers were processed for hematoxylin and eosin staining and liver steatosis was scored. Gonadal adipose tissue was extracted and weighed.ResultsTen weeks of HFD increased liver steatosis in WT males and females (PInteraction=0.84, PDiet=0.01, Psex=0.75, Table 1), but not in T cell deficient animals (PInteraction=0.35, PDiet=0.29, Psex=0.04). While HFD increased gonadal adipose tissue weight in both males and females, this weight was increased more in the females (PInteraction=0.006, PDiet<0.0001, Psex<0.0001). T cell deletion abolished the HFD‐induced weight gain in gonadal adipose tissue (PInteraction=0.98, PDiet=0.14, Psex=0.01).DiscussionThese data confirm the hypothesis that T cell KO prevents the HFD‐induced increases in adiposity in the liver and gonadal adipose tissue. Lipid deposits in these areas are detrimental for cardiovascular health. Lipid deposition in the liver is a strong predictor of insulin resistance. Furthermore, chronic ingestion of a HFD increases adipose tissue expansion, which promotes inflammation and oxidative stress. Since the majority of Americans are consuming large amounts of fat, investigating the mechanisms underlying HFD‐induced adiposity will help identify targets to improve cardiovascular health.