(A) The livers of Them2^–/– and Pctp^–/– mice are protected against ER stress due to high-fat feeding. Liver homogenates from high-fat-fed Them2^+/+ (n = 8), Them2^–/– (n = 9), Pctp^+/+ (n = 5), and Pctp^–/– (n = 5) mice were subjected to immunoblot analyses, and bands were quantified by densitometry and normalized to β-actin. Error bars represent SEM. *P < 0.05 compared with Them2^–/– or Pctp^+/+, ^‡P = 0.057 compared with Pctp^+/+. (B and C) Them2 and PC-TP modulate the resolution of hepatic ER stress following refeeding. Liver homogenates (n = 3 per genotype) were subjected to immunoblot analyses, and bands were quantified by densitometry. (D) The influence of refeeding on the interactions between PC-TP and Them2 was determined by coimmunoprecipitation in the liver lysates that were harvested from Pctp^+/+ (n = 3) mice, and bands were quantified by densitometry. (E–N) Them2 or PC-TP expression enables tunicamycin-induced liver injury. Eight-week-old chow-fed mice were injected i.p. with tunicamycin (0.25 mg/kg body weight) or vehicle (DMSO, 0.25% v/v) for 2 consecutive days. (E and F) Body weights (n = 3 per genotype) following tunicamycin injections (arrows). (G) Livers were harvested and imaged 6 hours following food restriction. Liver sections were subjected to hematoxylin and eosin (H&E) staining. Microscope images (×60) are representatives of n = 3. (H–M) Livers were analyzed for the concentrations of triglycerides (TG) (H and K), NEFA (I and L), and total cholesterol (J and M). (N) ER stress markers were detected in the liver lysates by immunoblot analyses. Error bars represent SEM. *P < 0.05 compared with WT. Statistical significance was determined by Student’s t test.