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KMID : 0811720090130060449
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Korean Journal of Physiology & Pharmacology
2009 Volume.13 No. 6 p.449 ~ p.454
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Overexpression of AMPKα1 Ameliorates Fatty Liver in Hyperlipidemic Diabetic Rats
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Seo Eun-Hui
Park Mi-Kyoung
Lee Hye-Jeong
Hong Sook-Hee
Kim Duk-Kyu
Park Eun-Jin
Joe Yeon-Soo
Kang Soo-Jeong
Kim Mi-Sun
Koh Hyong-Jong
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Abstract
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5’-AMP-activated protein kinase (AMPK) is a heterotrimeric complex consisting of a catalytic (?) and two regulatory (? and ?) subunits. Two isoforms are known for catalytic subunit (?1, ?2) and are encoded by different genes. To assess the metabolic effects of AMPK?1, we examined the effects of overexpression of adenoviral-mediated AMPK?1 in hyperlipidemic type 2 diabetic rats. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an established animal model of type 2 diabetes that exhibits chronic and slowly progressive hyperglycemia and hyperlipidemia. Thirty five-week-old overt type 2 diabetic rats (n=10) were administered intravenously with Ad.AMPK?1. AMPK activity was measured by phosphorylation of acetyl CoA carboxlyase (ACC). To investigate the changes of gene expression related glucose and lipid metabolism, quantitative real-time PCR was performed with liver tissues. Overexpression of AMPK?1 showed that blood glucose concentration was decreased but that glucose tolerance was not completely recovered on 7th day after treatment. Plasma triglyceride concentration was decreased slightly, and hepatic triglyceride content was markedly reduced by decreasing expression of hepatic lipogenic genes. Overexpression of AMPK?1 markedly improved hepatic steatosis and it may have effective role for improving hepatic lipid metabolism in hyperlipidemic state.
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KEYWORD
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AMP-activated protein kinase (AMPK), AMPKα1 catalytic subunit, Adenovirus, Type 2 diabetes, OLETF, Fatty liver
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