Overexpression of AMPKalpha1 Ameliorates Fatty Liver in Hyperlipidemic Diabetic Rats.
5'-AMP-activated protein kinase (AMPK) is a heterotrimeric complex consisting of a catalytic (alpha) and two regulatory (beta and gamma) subunits. Two isoforms are known for catalytic subunit (alpha1, alpha2) and are encoded by different genes. To assess the metabolic effects of AMPKalpha1, we examined the effects of overexpression of adenoviral-mediated AMPKalpha1 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.AMPKalpha1. 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 AMPKalpha1 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 AMPKalpha1 markedly improved hepatic steatosis and it may have effective role for improving hepatic lipid metabolism in hyperlipidemic state.
Seo
Eunhui
E
Department of Pharmacology, Medical Sciences Research Center, Dong-A University College of Medicine, Busan 602-714, Korea.
Park
Eun-Jin
EJ
Joe
Yeonsoo
Y
Kang
Soojeong
S
Kim
Mi-Sun
MS
Hong
Sook-Hee
SH
Park
Mi-Kyoung
MK
Kim
Duk Kyu
DK
Koh
Hyongjong
H
Lee
Hye-Jeong
HJ