Global Gdf15 deficiency alleviates the chemotherapy-induced anorexia and body weight loss. Related to Figs. 3 and 4. (A–D)Gdf15^KO (n = 5) and their littermates (Control, n = 5) were administered with one dose of Vehicle or DOX (5 mg per kg body weight, i.p.). (A) Gdf15 mRNA levels in livers; (B) circulating GDF15 protein levels; (C) daily food intake; (D) body weight change. (E–H)Gdf15^KO (n = 5) and their littermates (Control, n = 5) were administered with one dose of Vehicle or Cis (5 mg per kg body weight, i.p.). (E) Gdf15 mRNA levels in livers; (F) circulating GDF15 protein levels; (G) daily food intake; (H) body weight change. (I) mRNA levels of Gdf15 in Hepa1-6 cells infected with AAV-shNC, AAV-shGdf15-1, or AAV-shGdf15-2 for 48 h (n = 4 per group). (J) mRNA levels of Gdf15 in the indicated mouse tissues 4 wk after the injection of AAV-shNC (n = 3) or AAV-shGdf15 (n = 3). (K)Xbp1 mRNA splicing in various tissues isolated from mice treated with Vehicle (n = 6), DOX (n = 6), or Cis (n = 6). Tissues were collected 1 day after injection. gWAT, gonadal white adipose tissue; iWAT, inguinal white adipose tissue; TA, tibialis anterior; Gas, gastrocnemius. (L)XBP1 mRNA splicing in Huh7 cells transfected with control siRNA (si-NC) or siRNA against ERN1 (si-ERN1) prior to treatment with Vehicle or DOX (0.01 μg/ml) for 48 h. n = 3 per group. (M)XBP1 mRNA splicing in Huh7 cells transfected with control siRNA (si-NC) or siRNA against ERN1 (si-ERN1) prior to treatment with Vehicle or Cis (10 μM) for 48 h. n = 3 per group. Data are representative of two independent experiments (A–H and G) or three independent experiments (I–K) and presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 by unpaired two-tailed Student’s t test (A–H) one-way ANOVA (I–K) and two-way ANOVA (L and M).