Journal: Obesity (Silver Spring, Md.)
Article Title: The NLRP3 inhibitor NT ‐0796 enhances and sustains GLP ‐ 1R agonist‐mediated weight loss in a murine diet‐induced obesity model
doi: 10.1002/oby.24305
Figure Lengend Snippet: Effects of NT‐0796, semaglutide, or combinations in mice with DIO switched to a PUFA diet. Mice with DIO fed a HFD were dosed therapeutically with NT‐0796 (100 mg/kg, po, tid), semaglutide (0.005 mg/kg, sc, q.d), or a combination from day 0 to 28. On day 29, diet was switched to a PUFA diet, and the respective treatment continued (over days 29–56). An additional group of mice served as calorie‐restricted controls, body weight of which were maintained as closely to NT‐0796‐dosed mice as possible by controlling the degree of calorie restriction throughout the experiment. (A) Experimental schematic. (B) Percentage body weight change over time. An overnight fast into day 55 (dashed line) was performed for assessment of further exploratory endpoints. (C) Body weight over time. (D) Perirenal, (E) inguinal, (F) epididymal, and (G) total fat mass was assessed at study end (day 56). (H) Average daily food intake and (I) average daily calorie (kilocalories) intake during PUFA diet exposure (days 29–56). (J) Plasma IL‐1RA levels at study end (day 56). Data are expressed as mean ± SEM or as box and whisker plots and analyzed by one‐ or two‐way ANOVA with Tukey multiple comparisons test and significance calculated using GraphPad Prism version 10.2.2. **** p < 0.0001; *** p < 0.001; ** p < 0.01; and * p < 0.05. DIO, diet‐induced obesity; HFD, high‐fat diet; IL‐1RA, interleukin‐1 receptor antagonist; po, orally; PUFA, polyunsaturated fatty acid; qd, 1 time/day; sc, subcutaneously; tid, 3 times/day.
Article Snippet: Additional mouse cohorts were fed a diet enriched in polyunsaturated fatty acids (PUFA; 40% of kilocalories from fat; Dyets, Inc., category #D240510) [ ], which bears greater resemblance to the composition of a typical human diet.
Techniques: Clinical Proteomics, Whisker Assay
