Fig. 7: Animals with chronic liver steatosis show dysregulated MIER1 expression and improved liver regeneration upon MIER1 depletion.

a Liver TG analysis in animals fed with NCD or HFD for 8 weeks (crHFD) (Control, n = 15; crHFD, n = 25). b Immunoblots of liver MIER1 and EIF2S1 phosphorylation in crHFD animals before or after hepatectomy. c Immunoblots of MIER1 and EIF2S1 phosphorylation in primary hepatocytes from crHFD animals after PA (0.5 mM) treatment for 10 h. The liver/body weight ratio (%) (d) (n = 14), and liver Ki-67 immunostaining (e) (Control, n = 8; crHFD, n = 8; crHFD; Mier1 sgRNA, n = 9) in NCD, crHFD, and crHFD; Mier1 sgRNA animals at 48 h after hepatectomy. f Liver TG analysis in young (~8 weeks’ old) and aging (~12 months’ old) animals (Young, n = 12; Aging, n = 19). g Immunoblots of liver MIER1 and EIF2S1 phosphorylation in aging animals before or after hepatectomy. h Immunoblots of MIER1 and EIF2S1 phosphorylation in primary hepatocytes from aging animals after PA (0.5 mM) treatment for 10 h. The liver/body weight ratio (%) (i) (n = 8), and liver Ki-67 immunostaining (j) (Young, n = 5; Aging, n = 6) in aging, and aging; Mier1 sgRNA animals at 48 h after hepatectomy. k The mechanistic model illustrating the function of acute liver steatosis in promoting liver regeneration via MIER1. In healthy liver, after the onset of liver regeneration, the liver transiently accumulates lipids, which leads to attenuated Mier1 translation. MIER1 downregulation in turn promotes cell cycle gene expression and cell proliferating; Whereas in aging or fatty liver, the signaling function of liver lipids is impaired and the MIER1 regulation is compromised, resulting in repressed cell cycle gene expression and liver regeneration. Values represent means with SEM. P values were assessed by unpaired, two-tailed Student’s t test (a, f, i, j) or One-Way ANOVA with Dunnett’s multiple comparisons test (d, e). The experiments were repeated twice with similar results (b, c, g, h). The average values of the quantification of western blots were indicated (b, c, g, h). Source data are provided as a Source Data file.