Figure 7.

Execution of an auxiliary integrated stress response to dietary sulfur amino acid restriction (SAAR) delays but does not block induction of fibroblast growth factor 21 (FGF21). (A, B) Relative ratios of phosphorylated (p-S51) eukaryotic initiation factor 2α (eIF2α) to eIF2α (bottom) and representative lanes (top) for male (A) and female (B) wild-type (WT) and Atf4 whole-body knockout (Atf4KO) mice fed either a control (Ctrl) diet or subjeted to dietary SAAR for 5 wk. Results are expressed as relative to WT Ctrl for each biological sex. (C, D) Hepatic mRNA levels of Atf3, Atf4, Atf5, Asns, and Chop in male (C) and female (D) mice at the end of the 5-wk experimental period, relative to WT Ctrl for each biological sex. (E, F) Serum concentrations of FGF21 (ng/mL) at the end of the 5-wk experimental period in male (E) and female (F) WT and Atf4KO mice. (G) Hepatic expression levels of Fgf21 mRNA in male and female WT and Atf4KO mice after a 12-h experimental period, displayed as relative to the control-fed WT group. (H) Serum concentrations of FGF21 (ng/mL) in male and female WT and Atf4KO mice after a 12-h experimental period. n = 2–11/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. 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.