Obesity affects 40% of U.S. adults and is a major contributor to increased risk of disease and mortality. The Western diet, high in saturated fats, is increasingly linked to adipose tissue expansion, yet there are critical gaps in knowledge in understanding the mechanisms driving this expansion. The NLRP3 inflammasome is known to contribute to adipose tissue inflammation by acting as a metabolic sensor, yet less is known regarding the impact of NLRP3 on adipose tissue deposition and expansion. The goal of this experiment is to test the hypothesis that NLRP3 contributes to high fat diet (HFD)-induced increases in body fat composition. To test this hypothesis, male and female wildtype (WT) and NLRP3 knockout (KO) Dahl rats were studied. Rats were weaned at ~21 days of age and maintained on the AIN purified diet (n=5-8/group). At 5 weeks of age, rats were randomized to receive either a normal fat-diet (NFD; Bio-Serv F4031; 7.2% of calories from lard) or a HFD (Bio-Serv F3282; 36% of calories from lard) for 10 weeks. Rats were weighed weekly. NMR was performed at the end of dietary treatment to measure body fat composition and gonadal fat pads were collected and weighed. Data were compared via 2-way ANOVA within each sex. In addition, NLPR3 was measured in plasma samples from healthy weight and obese men and women via ELISA (n=40). There were no differences in starting body weights between WT or NLRP3 KO female rats (Pgenotype=0.34). HFD resulted in greater increases in body weight vs NFD in both WT and KO female rats (Pdiet=0.023, Pgenotype=0.083, Pdiet×genotype=0.59). In contrast, WT males were heavier at the start of the dietary treatment vs KOs (Pgenotype< 0.0001). A 10 wk HFD resulted in greater increases in body weight vs. NFD in males of both genotypes, yet WT males were heavier throughout the treatment (Pdiet=0.0003, Pgenotype< 0.0001, Pdiet×genotype=0.24). Body fat composition was measured at the end of the 10 wk dietary treatment. HFD resulted in greater increases in body fat vs. NFD in both females (Pdiet=0.003) and males (Pdiet=0.0007). In both sexes HFD-induced increases in body fat was greater in WT vs. KO rats (females: Pgenotype=0.0007, Pdiet×genotype=0.36; males: Pgenotype< 0.0001, Pdiet×genotype=0.9) despite consuming comparable amounts of dietary fat. Gonadal adipose tissue was isolated and weighed at the end of the treatment. Adipose tissue weight was greater following a HFD vs NFD in WT and KO females (Pdiet=0.0055) yet was lower in female KO vs. WT on both diets (Pgenotype=0.0003, Pdiet×genotype=0.81). In males, HFD resulted in greater adipose tissue weight only in WT (Pdiet< 0.0001, Pgenotype< 0.0001, Pdiet×genotype=0.032). Consistent with the notion that NLRP3 may be a imporatnt target for obesity-induced disorders, obese individuals have greater plasma NLRP3 than normal weight individuals. (ng/ml: 793±55vs 641±45, P=0.03). In conclusion, our findings support a role for NLRP3 to mediate HFD-induced increases in adiposity. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Kennedy et al. (Fri,) studied this question.