Decreased microsomal triglyceride transfer protein activity contributes to initiation of alcoholic liver steatosis in rats
| Autor: | Taizo Sugimoto, Shizuya Yamashita, Masato Ishigami, Yuji Matsuzawa, Kunio Matsumoto, Toshikazu Nakamura, Minoru Tahara, Ken-ichi Hirano, Naohiko Sakai |
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| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Carcinoma Hepatocellular Liquid diet Gene Expression Biology Microsomal triglyceride transfer protein Rats Sprague-Dawley chemistry.chemical_compound Internal medicine Phospholipid transfer protein Coenzyme A Ligases Tumor Cells Cultured medicine Animals Humans RNA Messenger Triglycerides Apolipoproteins B Ethanol Hepatology Triglyceride Hepatocyte Growth Factor Liver Neoplasms Fatty liver Central Nervous System Depressants medicine.disease Recombinant Proteins Rats Cholesterol Endocrinology Liver chemistry biology.protein Alcoholic fatty liver Steatosis Carrier Proteins Fatty Liver Alcoholic |
| Zdroj: | Journal of Hepatology. 36:157-162 |
| ISSN: | 0168-8278 |
| Popis: | To elucidate the role of microsomal triglyceride transfer protein (MTP) in the pathogenesis of alcoholic fatty liver, the effects of ethanol on MTP activity and gene expression were investigated.Male Sprague-Dawley rats fed an ethanol-containing liquid diet for 37 days, respectively, showed 2.9- and 4.9-fold increases in hepatic cholesterol and triglyceride content in comparison with rats fed an isocaloric ethanol-free diet (P0.01). Furthermore, a significant decrease in MTP activity and mRNA expression (by 27 and 58%, respectively) was observed after ethanol administration. Intravenous injection of human recombinant hepatocyte growth factor (hrHGF) on each of the last 7 days markedly suppressed ethanol-induced lipid accumulation in the liver. This inhibition of fatty change by hrHGF was accompanied by recovery of MTP activity and gene expression. No inhibitory effect of hrHGF on ethanol-induced acyl-CoA synthetase activation was observed. Experiments using human hepatoma-derived HepG2 cells indicated a direct positive effect of hrHGF on MTP gene expression as well as apolipoprotein B secretion.These results suggest that reduced MTP activity is crucial to development of alcoholic fatty liver, while promotion of MTP activity by HGF might serve as a therapeutic measure against alcoholic liver steatosis. |
| Databáze: | OpenAIRE |
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