BACKGROUND: The 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. METHODS: 5-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. RESULTS: Ten 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). DISCUSSION: These 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.
|Original language||English (US)|
|Journal||FASEB journal : official publication of the Federation of American Societies for Experimental Biology|
|State||Published - May 1 2022|
ASJC Scopus subject areas
- Molecular Biology