Six to eight weeks old male C57Bl6/J mice fed on high-fat high carbohydrate (HF2) diet for 32 weeks. (A) HF2-fed mice gain more bodyweight compared to chow-fed mice. HF2-fed mice at 8th,16th, and 32nd week on diet have higher (B) fasting blood glucose concentration (mg/dL); (C) plasma alanine aminotransferase (ALT) concentration (IU/L) and (D) hepatic triglyceride concentration (mg/100 mg liver tissues) compared to chow-fed mice. (E) Representative histological image of the liver section showing increased hepatic steatosis HF2-fed mice compared to chow-fed mice. (F) HF2-fed mice have shown a progressive increase in hepatic steatosis, inflammation, and ballooning score at 8th, 16th, and 32nd week compared to chow-fed mice. (G) Representative Masson’s Trichrome stained liver section showing hepatic fibrosis in HF2-fed mice at 32nd week on diet. (H) 80% of mice fed on the HF2 diet for 32 weeks have developed hepatic fibrosis. (I) HF2-fed mice have shown higher expression of hepatic ER stress marker PERK and Chop, a downstream target of PERK mediated ER stress pathway at 8th, 16th, and 32nd week compared to chow-fed mice. Mean ± SEM. ****P < 0.0001; ***P < 0.001; **P < 0.01; *P < 0.05.