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Am J Physiol Gastrointest Liver Physiol 293: G894-G902, 2007. First published August 16, 2007; doi:10.1152/ajpgi.00133.2007
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LIVER AND BILIARY TRACT

Involvement of AMP-activated protein kinase in beneficial effects of betaine on high-sucrose diet-induced hepatic steatosis

Zhenyuan Song,1 Ion Deaciuc,1 Zhanxiang Zhou,1 Ming Song,1 Theresa Chen,2 Daniell Hill,1 and Craig J. McClain1,2,3

1Departments of Medicine, 2Pharmacology and Toxicology, University of Louisville, and 3Louisville VA Medical Center, Louisville, Kentucky

Submitted 22 March 2007 ; accepted in final form 13 August 2007

Although simple steatosis was originally thought to be a pathologically inert histological change, fat accumulation in the liver may play a critical role not only in disease initiation, but also in the progression to nonalcoholic steatohepatitis and cirrhosis. Therefore, prevention of fat accumulation in the liver may be an effective therapy for multiple stages of nonalcoholic fatty liver disease (NAFLD). Promising beneficial effects of betaine supplementation on human NAFLD have been reported in some pilot clinical studies; however, data related to betaine therapy in NAFLD are limited. In this study, we examined the effects of betaine on fat accumulation in the liver induced by high-sucrose diet and evaluated mechanisms by which betaine could attenuate or prevent hepatic steatosis in this model. Male C57BL/6 mice weighing 20 ± 0.5 g (means ± SE) were divided into four groups (8 mice per group) and started on one of four treatments: standard diet (SD), SD+betaine, high-sucrose diet (HS), and HS + betaine. Betaine was supplemented in the drinking water at a concentration of 1% (wt/vol) (anhydrous). Long-term feeding of high-sucrose diet to mice caused significant hepatic steatosis accompanied by markedly increased lipogenic activity. Betaine significantly attenuated hepatic steatosis in this animal model, and this change was associated with increased activation of hepatic AMP-activated protein kinase (AMPK) and attenuated lipogenic capability (enzyme activities and gene expression) in the liver. Our findings are the first to suggest that betaine might serve as a therapeutic tool to attenuate hepatic steatosis by targeting the hepatic AMPK system.

fatty liver; triglyceride; methionine; homocysteine; adiponectin



Address for reprint requests and other correspondence: Z. Song, The Liver Research Center, Dept. of Medicine, Univ. of Louisville Medical Center, Louisville, KY 40292 (e-mail: z0song02{at}louisville.edu)




This article has been cited by other articles:


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Therapeutic Advances in GastroenterologyHome page
S. Chitturi
Review: Treatment options for nonalcoholic fatty liver disease
Therapeutic Advances in Gastroenterology, November 1, 2008; 1(3): 173 - 189.
[Abstract] [PDF]




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