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Dietary fat source alters hepatic gene expression profile and determines the type of liver pathology in rats overfed via total enteral nutrition

To determine if dietary fat type influences nonalcoholic fatty liver disease (NAFLD), male SD rats were overfed low (5%) or high (70%) fat diets containing olive oil (OO), corn oil (CO) or echium oil (EO) using total enteral nutrition (TEN) for 21 d. Overfeeding 5% CO or 5% EO diets resulted in less steatosis than 5% OO (P< 0.05). Significant differences in hepatic gene expression signatures were associated with greater fatty acid synthesis, ChREBP and SREBP‐1c signaling, and increased fatty acid transport (P<0.05) in the 5% OO compared to 5% CO group. The OO groups had macrosteatosis, but no evidence of oxidative stress or necrosis. The 70% CO and 70% EO groups had a mixture of micro‐ and macrosteatosis or only microsteatosis, respectively; increased oxidative stress; and increased necrotic injury relative to their respective 5% groups (P<0.05). Oxidative stress and necrosis correlated with peroxidizability of hepatic triglycerides. Increased antioxidant pathways and lower expression of genes linked to inflammation and fibrosis were observed in the 70% OO relative to the 70% CO group. When 70% OO diet was overfed for 50 d there was no progression of injury beyond simple steatosis. Therefore, dietary fat type influences the progression of NAFLD and a Mediterranean diet high in olive oil may reduce the risk of NAFLD progressing to nonalcoholic steatohepatitis. Supported in part by USDA, ARS‐CRIS 6251–51000‐005–004S.