Figure 4.

GDF15 Is Upregulated in Response to a Lysine-Deficient Diet and Induces Conditioned Taste Aversion in Mice

(A–D) Mouse Study 4 (MS4): (A) GDF15 serum concentrations and (B) ATF4, (C) CHOP, and (D) GDF15 mRNA expression in livers of 11- to 12-week-old female mice that were fasted overnight and then fed a control chow (Con) or lysine-deficient diet (−Lys) for 4 h. A blood sample was withdrawn at 1 h following the beginning of the meal. Serum and mRNA (4 h time point only) data are expressed as mean ± SEM (n = 6 mice per group) with mRNA normalized to B2M gene expression. ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001 by one-way ANOVA.

(E) Mouse Study 5 (MS5): Circulating plasma GDF15 concentrations after a single dose of recombinant GDF15 in mice; dose response (n = 3/ group).

(F and G) Cumulative food intake measured between 1 and 4 h post-GDF15 dose expressed as total grams (F) or percent (%) of vehicle control (G) (n = 7–8/group). Data are presented as mean ± SEM. ^∗∗∗∗p < 0.0001 versus vehicle by one-way ANOVA with Bonferroni multiple comparison post-test.

(H) Saccharin and water consumption during conditioned taste aversion test during GDF15 treatment (n = 8–16/group). Data are presented as mean ± SEM and analyzed using a two-way ANOVA with Bonferroni multiple comparison post-test to compare proportion of saccharin water and water consumption between groups of GDF15 or LiCl treatment to vehicle. ^∗∗∗∗(saccharin) or ^####(water) p < 0.0001. See also Figure S4.