Overexpression of AMPKalpha1 Ameliorates Fatty Liver in Hyperlipidemic Diabetic Rats.
10.4196/kjpp.2009.13.6.449
- Author:
Eunhui SEO
1
;
Eun Jin PARK
;
Yeonsoo JOE
;
Soojeong KANG
;
Mi Sun KIM
;
Sook Hee HONG
;
Mi Kyoung PARK
;
Duk Kyu KIM
;
Hyongjong KOH
;
Hye Jeong LEE
Author Information
1. Department of Pharmacology, Medical Sciences Research Center, Dong-A University College of Medicine, Busan 602-714, Korea. hjlee@dau.ac.kr
- Publication Type:Original Article
- Keywords:
AMP-activated protein kinase (AMPK);
AMPKalpha1 catalytic subunit;
Adenovirus;
Type 2 diabetes;
OLETF;
Fatty liver
- MeSH:
Acetyl Coenzyme A;
Adenoviridae;
AMP-Activated Protein Kinases;
Animals;
Blood Glucose;
Catalytic Domain;
Fatty Liver;
Gene Expression;
Glucose;
Hyperglycemia;
Hyperlipidemias;
Lipid Metabolism;
Liver;
Models, Animal;
Phosphorylation;
Plasma;
Protein Isoforms;
Rats;
Real-Time Polymerase Chain Reaction
- From:The Korean Journal of Physiology and Pharmacology
2009;13(6):449-454
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
