Abstract
We aim to investigate the preventive and therapeutic effects of ghrelin on a rat NAFLD model and possible underlying mechanism. Sprague-Dawley rats were fed with high-fat diet for 8weeks to induce NAFLD. A group of rats were also treated with ghrelin throughout the NAFLD induction. After 8weeks, rats were sacrificed for liver injury measurements. Rats with NAFLD showed obvious histological changes including necrosis and inflammation foci, elevated serum enzyme (ALT and AST) levels, dysregulated hepatic lipid metabolism, increased formation of oxidative stress, and lipid peroxidation markers, up-regulated levels of pro-inflammatory cytokines and apoptotic cells in the liver. Treatment of ghrelin improved liver injury through counter-acting those events. The improvement of ghrelin was accompanied with a restoration of LKB1/AMPK and PI3K/Akt pathways. Ghrelin treatment alone did not influence the healthy rat liver. In addition, "therapeutic" ghrelin administration (2weeks) after the establishment of early NAFLD symptoms (4weeks) in rats further proved the beneficial effects of ghrelin. In conclusion, administration of ghrelin could attenuate NAFLD-induced liver injury, oxidative stress, inflammation, and apoptosis partly through the action of LKB1/AMPK and PI3K/Akt pathways.
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