Study design. (A) We used a diet-induced mouse model of NAFLD (Asgharpour et al. 2016). Heterozygous 8- to 12-wk-old C57BL/6J (B6)/129S1/SvImJ (S129) mice were fed a western diet (WD; 42% kcal from fat and containing 0.1% cholesterol; Harlan TD.88137) with ad libitum consumption of glucose and fructose (SW; 23.1 g/L d-fructose +18.9 g/L d-glucose) for 8 wk (WD8) and 12 wk (WD12), when the animals developed mild and severe steatosis, respectively. Nuclear shape was determined by DAPI staining, liver histology by hematoxylin and eosin (H&E) staining, and expression of lamina proteins by western blot. Lamin B1 and FOXA2 ChIP-seq were performed to identify LADs and pioneer factor binding. Differential expression on different diets was determined by RNA-seq. (B) Liver tissue samples from donors (three healthy, three NAFLD with mild steatosis, and three NAFLD with severe steatosis; healthy, 26–45 yr old; NAFLD, 21–51 yr old) were obtained from Sekisui XenoTech Biobank. Nuclear shape was determined by DAPI staining, liver histology by H&E staining, and expression of lamina proteins by western blot. Lamin B1 and FOXA2 ChIP-seq were performed to identify LADs and pioneer factor binding.
