Effects of RAGE229–150 ppm diet on body and fat mass and metabolic benefits are sex-independent: studies in female mice. (A) Experimental schematic. (B) Body mass recorded over the indicated time course in female lean mice fed base diet until age 26 weeks; mice then remained on base diet (n = 14) or were switched to RAGE229–150 ppm diet (n = 13) for 6 weeks. (C) Change in body mass (%) over 6 weeks after diet switch. (D) Adipose tissue depot mass (n = 14 base diet, n = 13 RAGE229–150 ppm diet) at 8 weeks after diet switch. (E) Post-6-hour fasting glucose tolerance test at 6 weeks after diet switch (n = 14 base diet, n = 13 RAGE229–150 ppm diet). (F–H) Post-6-hour fasting plasma glucose, insulin, and HOMA-IR at 8 weeks after diet switch (n = 14 base diet, n = 13 RAGE229–150 ppm diet). (I) Relative expression of indicated metabolic and thermogenic genes in iWAT collected from mice fasted for 6 hours (n = 8 per group) at 8 weeks after diet switch. Data are presented as the mean ± SEM. For analysis of absolute body mass (panel B) over the indicated time period, piecewise linear mixed-effect model was fitted, with node set at 26 weeks, and difference was tested between the body mass of the weight of base diet and RAGE229–150 ppm diet groups after diet switch. Linear mixed-effect model was adopted for correlated/time-series data (B,C,E) with post hoc t test for group comparisons at each time point. For group comparison, the Shapiro–Wilk normality test was conducted first for each group, with prespecified significance level of 0.1, and if passed, the t test was implemented whereas the nonparametric Kruskal-Wallis test/Wilcoxon rank sum test was used if normality was not established. AUC, area under the curve; HOMA-IR, homeostatic model assessment of insulin resistance; iWAT, inguinal white adipose tissue; pWAT, perigonadal white adipose tissue; iBAT, interscapular brown adipose tissue; RAGE229, receptor for advanced glycation end products. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001 [Color figure can be viewed at wileyonlinelibrary.com]