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Original Article Rosiglitazone Activates AMPK and Improves Non-Alcoholic Fatty Liver Disease in OLETF Rats.
Eun Hee Cho, Ki Up Lee
Diabetes & Metabolism Journal 2008;32(2):141-148
DOI: https://doi.org/10.4093/kdj.2008.32.2.141
Published online: April 1, 2008
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Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Korea.

BACKGROUND
Insulin resistance is very common in patients with nonalcoholic fatty liver disease (NAFLD). Glitazones improve insulin sensitivity by acting as a selective agonist of the peroxisome proliferators -activated receptor gamma (PPAR gamma), and were shown to activate AMP-activated protein kinase (AMPK) in skeletal muscle and the liver. Glitazones were also shown to reduce hepatic lipogenesis. The aim of this study was to investigate whether the protective mechanism of rosiglitazone on NAFLD is associated with AMPK activation. METHODS: Twelve OLETF rats were divided into 2 groups (control, treatment, n = 6 each). LETO rats served as controls. At 35 weeks of age, treatment group received rosiglitazone 4 mg/kg daily for 3 days. Fasting plasma glucose, insulin, free fatty acid, lactate and triglycerides were measured. Liver tissues from each group were processed for histological and hepatic triglyceride content analysis and western blotting. RESULTS: Fasting plasma glucose, insulin and triglycerides levels were significantly lower in treatment group than in control group. Histologic examination disclosed decreased hepatic steatosis in treatment group. Hepatic triglyceride content was also decreased in treatment group. Sterol regulatory binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) expression were increased and AMPK phosphorylation was reduced in OLETF rats compared with LETO rats, and these changes were reversed by rosiglitazone treatment. CONCLUSION: Rosiglitazone reduced hepatic steatosis in OLETF rats, and activated AMPK in the liver. These results suggest the role of AMPK activation in the protective action of rosiglitazone on NAFLD.

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    Rosiglitazone Activates AMPK and Improves Non-Alcoholic Fatty Liver Disease in OLETF Rats.
    Korean Diabetes J. 2008;32(2):141-148.   Published online April 1, 2008
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