Hepatic IRE1α ablation alleviates chemotherapy-induced anorexia and body weight loss. (A) Western blot analysis of the indicated proteins in liver lysates from flox/flox (Ern1loxP/loxP, littermate controls) and LKO (Ern1loxP/loxP; Albumin-Cre) mice treated with a single dose of Vehicle or DOX (5 mg per kg body weight, i.p.). Liver samples were collected 1 day after injection. Each sample represents an individual animal. Tubulin was used as a loading control. (B and C) Daily food intake (B) and body weight changes (C) of the indicated groups following Vehicle (Veh.) or DOX injection. flox/flox+Veh., n = 6; LKO+Veh., n = 6; flox/flox+DOX, n = 6; LKO+DOX, n = 7. Yellow arrows indicate the time points of DOX injection (5 mg per kg body weight, i.p.). (D) Western blot analysis of the indicated proteins in liver lysates from flox/flox and LKO mice treated with a single dose of Vehicle or Cis (5 mg per kg body weight, i.p.). Liver samples were collected 1 day after injection. Each sample represents an individual animal. Tubulin was used as a loading control. (E and F) Daily food intake (E) and body weight changes (F) of the indicated groups following Vehicle (Veh.) or Cis injection. flox/flox+Veh., n = 6; LKO+Veh., n = 6; flox/flox+Cis, n = 8; LKO+Cis, n = 7. Brown arrows indicate the time points of Cis injection (5 mg per kg body weight, i.p.). (G) Schematic illustration of the experimental design. 8-wk-old male flox/flox and LKO mice were subcutaneously inoculated with Hepa1-6 cells to induce tumor formation. DOX (5 mg per kg body weight) or Vehicle was i.p. administered, and visible tumors were removed by surgery at the indicated time. (H) Body weight changes in tumor-bearing and -resected flox/flox and LKO mice treated with Vehicle or DOX. flox/flox+Veh., n = 10; LKO+Veh., n = 8; flox/flox+DOX, n = 12; LKO+DOX, n = 10. Yellow arrow indicates the time point of tumor removal. Black arrows indicate the time points of DOX or Vehicle treatment. Data are representative of two independent experiments and presented as mean ± SEM. **P < 0.01, or ***P < 0.001 by unpaired two-tailed Student’s t test (B, C, E, F, and H). Source data are available for this figure: SourceData F2.
Figure 2.

Hepatic IRE1α ablation alleviates chemotherapy-induced anorexia and body weight loss. (A) Western blot analysis of the indicated proteins in liver lysates from flox/flox (Ern1loxP/loxP, littermate controls) and LKO (Ern1loxP/loxP; Albumin-Cre) mice treated with a single dose of Vehicle or DOX (5 mg per kg body weight, i.p.). Liver samples were collected 1 day after injection. Each sample represents an individual animal. Tubulin was used as a loading control. (B and C) Daily food intake (B) and body weight changes (C) of the indicated groups following Vehicle (Veh.) or DOX injection. flox/flox+Veh., n = 6; LKO+Veh., n = 6; flox/flox+DOX, n = 6; LKO+DOX, n = 7. Yellow arrows indicate the time points of DOX injection (5 mg per kg body weight, i.p.). (D) Western blot analysis of the indicated proteins in liver lysates from flox/flox and LKO mice treated with a single dose of Vehicle or Cis (5 mg per kg body weight, i.p.). Liver samples were collected 1 day after injection. Each sample represents an individual animal. Tubulin was used as a loading control. (E and F) Daily food intake (E) and body weight changes (F) of the indicated groups following Vehicle (Veh.) or Cis injection. flox/flox+Veh., n = 6; LKO+Veh., n = 6; flox/flox+Cis, n = 8; LKO+Cis, n = 7. Brown arrows indicate the time points of Cis injection (5 mg per kg body weight, i.p.). (G) Schematic illustration of the experimental design. 8-wk-old male flox/flox and LKO mice were subcutaneously inoculated with Hepa1-6 cells to induce tumor formation. DOX (5 mg per kg body weight) or Vehicle was i.p. administered, and visible tumors were removed by surgery at the indicated time. (H) Body weight changes in tumor-bearing and -resected flox/flox and LKO mice treated with Vehicle or DOX. flox/flox+Veh., n = 10; LKO+Veh., n = 8; flox/flox+DOX, n = 12; LKO+DOX, n = 10. Yellow arrow indicates the time point of tumor removal. Black arrows indicate the time points of DOX or Vehicle treatment. Data are representative of two independent experiments and presented as mean ± SEM. **P < 0.01, or ***P < 0.001 by unpaired two-tailed Student’s t test (B, C, E, F, and H). Source data are available for this figure: SourceData F2.

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