Sex- and diet-specific effects of Pirt deficiency on energy metabolism. Body weight progression of female wild-type (WT) (black) and Pirt−/− (KO) (grey) mice on a standard chow (A) and high-fat, high-sugar (HFHS) diet (B). Fat mass (C) and lean mass (D) of the female cohorts at 27 weeks of age. Body weight progression of male WT and Pirt−/− mice on a standard chow (E) and HFHS diet (F). Fat mass (G) and lean mass (H) of the male cohorts at 27 weeks of age. Energy expenditure (I), respiratory exchange ratio (RER) (J), and mean locomotor activity (K) of female chow-fed WT and Pirt−/− mice at 27 weeks of age. Average daily food intake in female chow-fed WT and Pirt−/− mice from week 8 to week 25 of age (L). Phenotyping cohorts with n = 8 per sex, diet, and genotype. Data represent mean ± s.e.m. Data presented in longitudinal graphs (A,B,E,F,I,J) were analyzed by two-way ANOVA (genotype and time) and data presented in bar graphs (C,D,G,H,K,L) were analyzed by two-way ANOVA (genotype and diet) or an unpaired two-tailed Student's t-test comparing WT with Pirt−/− mice. ANOVA was followed by Bonferroni post hoc multiple comparison analysis to determine statistical significance. *P < 0.05, **P < 0.01 effects of genotype within the diets and $P < 0.05 main effects of genotype irrespective of diet.