Intermittent Fasting and Caloriec Restriction Ameliorate High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease in Male Albino Rats: Targeting PPARα and HNF4α Pathways

Background: This study aimed to assess the impacts of a high-fat diet (HFD) on Nonalcoholic fatty liver disease (NAFLD) and intermittent fasting and caloric restriction in an obesity-induced rat model, focusing on peroxisome proliferator-activated receptor alpha (PPARα) and hepatocyte nuclear factor 4α (HNF4α) pathways. Methods: The experiment involved 66 male Wistar rats, were allocated into six groups: Normal Control (NC): Fed normal chow diet for 16 weeks while after 12 weeks of HFD NAFLD Model: followed by four more weeks on HFD to induce NAFLD, NAFLD-ND (Reversal): switched to normal chow for 4 weeks, Time-Restricted Feeding (TRF): normal chow with time-restricted eating (8 p.m. to 8 a.m.) for 4 weeks, Alternate day fasting (ADF): normal chow with alternating 24-hour feeding and water-only fasting for 4 weeks and calorie Restriction (CR): normal chow with 70% of the NC group's diet for 4 weeks. Results: The NAFLD model group had significantly increased BW, visceral fat, liver index, liver enzymes, fasting blood sugar (FBG), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), cholesterol, low and very low-density lipoprotein, and lower high-density steatosis, with decreased fatty acid oxidation (FAO) and lipid exportation gene expression. The NAFLD-ND group showed reduced liver index, enzymes, and hepatic vacuolations, but no significant changes in body weight, fat, FBG, insulin, HOMA-IR, or lipids. Conclusions: A normal diet alone reduces liver steatosis in HFD-induced NAFLD but doesn't fully resolve obesity or metabolic issues, while TRF, ADF, and CR, with a normal diet, improve both metabolic health and NAFLD markers.