期刊
JOURNAL OF HEPATOLOGY
卷 53, 期 6, 页码 1108-1116出版社
ELSEVIER
DOI: 10.1016/j.jhep.2010.05.034
关键词
Liver injury; Adiponectin; Rosiglitazone; Mitochondria; Uncoupling protein 2
资金
- Research Grants Council of Hong Kong [777908M]
- National Basic Research Program of China [2010CB945500 2011CB504004]
- University Grants Committee HKSAR [AoE/P-10-01]
- US National Institutes of Health [HL-51586]
Background & Aims The beneficial effects of rosiglitazone on non-alcoholic fatty liver disease (NAFLD) have been reported Rosiglitazone treatment stimulates the production of adiponectin an insulin-sensitizing adipokine with hepatoprotective functions The present study aims to investigate the hepatic actions of rosiglitazone in mice without adiponectin Methods NAFLD was induced in wild type and adiponectin knockout (AKO) mice by high-fat diet feeding After rosiglitazone treatment mice were subjected to evaluations on systemic insulin sensitivity lipid profiles hepatic steatosis and inflammation as well as the expression and activity of key molecules Involved in energy metabolism and mitochondrial functions Results Rosightazone treatment prevented hepatic inflammation and reduced the expression of pro-inflammatory cytokines in livers of wild type mice In contrast in livers of AKO mice the same treatment induced severe hepatomegaly and microvesicular hepatosteatosis and caused abnormal accumulation of fatty acyl CoA glycogen and their intermediate metabolites Compared to wild type littermates the anti-inflammatory and the mitochondria-stimulatory activity of rosiglitazone were largely attenuated in AKO mice Replenishment with either adiponectin or uncoupling protein 2 (UCP2) significantly reduced fatty acyl CoA accumulation and increased mitochondrial activities in livers of rosiglitazone-treated AKO mice In addition adiponectin but not UCP2 promoted the activation of glycogen synthase kinase 3beta (GSK3beta) a key molecule Involved in regulating glycogen homeostasis Conclusions Rosiglitazone elicits its protective functions against NAFLD largely through the induction of adiponectin which prevents mitochondria stresses by promoting GSK3beta activation and UCP2 upregulation two pathways coordinating the glucose and lipid metabolism in liver (C) 2010 European Association for the Study of the Liver Published by Elsevier B V All rights reserved
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