Figure 8.

Global loss of Atf4 disrupts endogenous hydrogen sulfide (H₂S) production during dietary sulfur amino acid restriction (SAAR) in male mice only. (A, B) Hepatic concentrations of endogenous H₂S production capacity in male (A) and female (B) wild-type (WT) and whole-body Atf4 knockout (Atf4KO) mice, fed either a control (Ctrl) diet or subjected to dietary SAAR, displayed as relative to the Ctrl-fed WT group for each biological sex. (C, D) Hepatic Nrf2 mRNA levels in male (C) and female (D) WT and Atf4KO mice, shown as relative to the respective Ctrl-fed WT group. (E, F) Hepatic mRNA expression levels of Cbs, Cth, Slc7a11, and Slc3a2 in male (E) and female (F) WT and Atf4KO mice, displayed as relative to the Ctrl-fed WT group for each biological sex. n = 3–11/group. *P < 0.05 with a main effect of diet. ^#P < 0.05 with a main effect of genotype. n.s. indicates no statistically significant differences at α = 0.05, as determined by two-factor ANOVA. In case of a statistical interaction effect (between diet and genotype), groups not sharing a common letter indicate a statistically significant difference between groups as determined by post hoc analysis using pairwise t tests with Bonferroni correction. Data shown as part of bar charts are presented as mean ± SEM, with individual data points overlaid. Boxplots indicate median values, with upper and lower hinges representing the 25th and 75th percentiles, respectively, and with upper and lower whiskers reaching to the largest and smallest values, respectively, while not extending further than 1.5 times the interquartile range, with individual data points overlaid.