NLRP3 Contributes to High Fat Diet‐Induced Increases In Blood Pressure And Adiposity In Female Dahl Rats

Abstract

Background Chronic ingestion of a high-fat diet (HFD) is pro-inflammatory and has been linked to the development of hypertension. The NLRP3 inflammasome contributes to adipose tissue inflammation with a chronic HFD in males, yet the role in blood pressure (BP) control is unknown. Interestingly, there is increasing evidence that females are highly susceptible to cardiovascular complications following a chronic HFD. The Dahl rat is a model of HFD-induced hypertension and adiposity. The goal of the current study was to test the hypothesis that NLRP3 contributes to HFD-induced increases in BP in female Dahl rats. Methods 5-week-old female wildtype (WT; n=4-8) and NLRP3 knockout (KO; n=3-6) Dahl rats were randomized to either a control normal fat diet (NFD; 7.2% calories from fat) or high fat diet (HFD; 36% of calories from fat). Body weights were measured weekly. At 15 weeks of age, body fat mass was measured via nuclear magnetic resonance. Rats were then implanted with telemetry devices and BP was measured from 16-17 weeks of age. Results Following 10 weeks of treatment with HFD, body fat percentage increased in female WT Dahl rats, however HFD-induced increases in body fat were attenuated in NLRP3 KO rats (Table, PInteraction=0.04, PDiet=0.01, Pgenotype<0.0001). Despite significant differences in body fat, all groups had similar body weights following 10 weeks of dietary treatment (PInteraction=0.56, PDiet=0.24, Pgenotype=0.09). We confirmed that chronic consumption of HFD increased MAP in female WT Dahl rats vs rats on NFD. HFD-induced increases in MAP were attenuated in NLRP3 KO rats (PInteraction=0.02, PDiet=0.001, Pgenotype=0.28). Discussion Our findings indicate that NLRP3 contributes to chronic HFD-induced increases in body fat and MAP in female Dahl rats. Most Americans eat more than the recommended amount of saturated fat. Since decreasing the intake of saturated fats is difficult, more basic science research like this project is necessary to understand the mechanisms through which females on a HFD have compromised cardiovascular health.