Treatment with Ω-3 fatty acids but not exendin-4 improves hepatic steatosis

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the Western world. The aim of this study was to evaluate the biochemical and histological effects of Ω-3 fatty acid and exendin-4 treatment on NAFLD in an animal model. Methods: Sixty-three 8-week-old outbred Sprague-Dawley male rats were used for this study. Three animals were used as procedure controls, and 30 rats were fed a methionine and choline deficient (MCD) diet and 30 were fed a regular chow diet. In each group of 30 animals, 10 served as controls, 10 received exendin-4, and 10 received Ω-3 fatty acids. After 75 days of treatment, the animals were euthanized, the tissues and serum were harvested, and the livers were formalin-fixed for histology. Results: The MCD diet was exceptionally efficient at producing fatty livers. The MCD control animals had a liver steatosis score of 38±6.7 (of 50 possible); treatment with exendin-4 was not associated with a significant reduction of steatosis (44±5.16, P=0.07) and the Ω-3 fatty acid treatment was associated with a significant decrease in the liver steatosis score (15.6±13.46, P<0.001) compared with both the controls and the exendin-4 groups. The Ω-3 fatty acid treatment increased serum aspartate aminotransferase significantly, whereas exendin-4 had no effect. Conxlusion: In an animal model of NAFLD, the Ω-3 fatty acid therapy was associated with significant improvement in hepatic steatosis compared with exendin-4. These data suggest that Ω-3 fatty acid supplements may have a potential therapeutic role in patients with NAFLD.