title: Administration of ghrelin improves inflammation, oxidative stress, and apoptosis during and after non-alcoholic fatty liver disease development.
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 8 weeks to induce NAFLD. A group of rats were also treated with ghrelin throughout the NAFLD induction. After 8 weeks, 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 PI3 K/Akt pathways. Ghrelin treatment alone did not influence the healthy rat liver. In addition, "therapeutic" ghrelin administration (2 weeks) after the establishment of early NAFLD symptoms (4 weeks) 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 PI3 K/Akt pathways.
authors: Department of Endocrinology, First Affiliated Hospital, Xinxiang Medical University, Jiankang Road, Xinxiang City, Henan, China.
authors: Yan
authors: Y
authors: Li
authors: Jie
authors: J
authors: Hai
authors: Lake
authors: L
authors: Li
authors: Xuehui
authors: X
authors: Chen
authors: Hua
authors: H
authors: Peng
authors: Meng
authors: M
authors: Cao
authors: Qinggui
authors: Q
authors: Zhang
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D054439:Ghrelin / Q000494:pharmacology* / Q000627:therapeutic use*; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D000091162:AMP-Activated Protein Kinase Kinases; D000263:Adenylate Kinase; D054439:Ghrelin; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C488755:Stk11 protein, rat