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

Abstract

TM. Dietary fat source alters hepatic gene expression profile and determines the type of liver pathology in rats overfed via total enteral nutrition. Physiol Genomics 44: 1073-1089, 2012. First published September 18, 2012 doi:10.1152/physiolgenomics.00069.2012.-To determine if dietary fat composition affects the progression of nonalcoholic fatty liver disease (NAFLD), we overfed male Sprague-Dawley rats low (5%) or high (70%) fat diets with different fat sources: olive oil (OO), corn oil (CO), or echium oil (EO), with total enteral nutrition (TEN) for 21 days. Overfeeding of the 5% CO or 5% EO diets resulted in less steatosis than 5% OO (P Ͻ 0.05). Affymetrix array analysis revealed significant differences in hepatic gene expression signatures associated with greater fatty acid synthesis, ChREBP, and SREBP-1c signaling and increased fatty acid transport (P Ͻ 0.05) in the 5% OO compared with 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 Ͻ 0.05). Oxidative stress and necrosis correlated with increasing peroxidizability of the accumulated triglycerides. Affymetrix array analysis comparing the 70% OO and 70% CO groups revealed increased antioxidant pathways and lower expression of genes linked to inflammation and fibrosis in the 70% OO group. A second study in which 70% OO diet was overfed for 50 days produced no evidence of progression of injury beyond simple steatosis. These data suggest that dietary fat type strongly influences the progression of NAFLD and that a Mediterranean diet high in olive oil may reduce the risk of NAFLD progressing to nonalcoholic steatohepatitis. nonalcoholic steatohepatitis; fatty acid; lipid peroxidation; SREBP-1c; ChREBP NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) is increasingly recognized as a component of "metabolic syndrome," a cluster of pathologies associated with obesity (16). Characterized by initial fat accumulation (steatosis) in up to 70% of obese patients (68), NAFLD pathology can progress to include inflammation, apoptosis, necrosis, and fibrosis (nonalcoholic steatohepatitis, NASH) and ultimately cirrhosis and liver cancer (14). While nutrition and physical activity are clearly major factors in NAFLD development and progression, the exact role of diet composition in this process remains unclear (14, 40).Research in this area has been hampered by lack of an animal model that mimics the natural course and etiological background of NAFLD observed clinically (7, 40). In general, nutritionally relevant models in which obesity has been achieved as a result of ad libitum feeding of diets high in sugars, such as sucrose and fructose or in saturated fats, have resulted in simple steatosis with limited evidence of progressive injury (37,52,69). Moreover, uncontrolled differences in caloric intake and species and strain differen...

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Transcriptomics and the Mediterranean Diet: A Systematic Review

“…At the low fat content, compared with the corn oil group, differences in hepatic gene expression signatures associated with greater fatty acid synthesis, carbohydrate-responsive element-binding proteins, and SREBP-1c signaling, and increased fatty acid transport was observed in the olive oil group. With the higher fat diet (70%), when compared to the corn oil group, rats receiving the olive oil-enriched diet showed increased antioxidant pathways and lower expression of genes linked to inflammation and fibrosis, despite the increased macrosteatosis, but with no further hepatic damage [48]. Thereby, a Mediterranean diet high in olive oil may reduce the risk of non-alcoholic fatty liver disease progression to nonalcoholic steatohepatitis.…”

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