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Horm Metab Res 2010; 42(11): 769-774
DOI: 10.1055/s-0030-1263122
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Dietary Folic Acid Activates AMPK and Improves Insulin Resistance and Hepatic Inflammation in Dietary Rodent Models of the Metabolic Syndrome

R. Buettner1 , I. Bettermann1 , C. Hechtl1 , E. Gäbele1 , C. Hellerbrand1 , J. Schölmerich1 , L. C. Bollheimer1
  • 1Department of Internal Medicine I, University Medical Center Regensburg, Regensburg, Germany
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Publication History

received 13.01.2010

accepted 22.07.2010

Publication Date:
27 August 2010 (online)

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Abstract

The AMP activated kinase plays an important role in metabolic control, and pharmacologic enhancement of AMPK activity is used to improve insulin resistance. We hypothesized that high dose of folic acid supplementation might improve insulin sensitivity and hepatic inflammation and examined this by a dietary intervention in (a) the high fat fed rat model of the metabolic syndrome, which shows sole hepatic steatosis as well as (b) in rats fed with a high cholesterol, high cholate diet inducing nonalcoholic steatohepatitis (NASH). Male Wistar rats were fed with folic acid supplemented (40 mg/kg) high fat diet [based on lard, fat content 25% (wt/wt)] or NASH inducing diet (containing 15% fat, 1.25% cholesterol, 0.5% sodium cholate). Metabolic profiling was performed by measuring the animals’ visceral fat pads, fasting plasma glucose, insulin, and adipokines as well as in vivo insulin tolerance tests. Hepatic steatosis and inflammation were analyzed semiquantitatively by histological analysis. Folic acid supplementation reduced visceral obesity and improved plasma adiponectin levels. In vivo insulin sensitivity was improved, and in HF-FA rats folic acid increased activation of hepatic AMPK. Further, folic acid supplementation improved hepatic inflammation in animals fed with NASH-inducing diet. Dietary folic acid improved parameters of insulin resistance and hepatic inflammation in rodent models. This might be due to an increased AMK activation.

Key words

folate - nonalcoholic steatohepatitis - insulin action

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Correspondence

R. BuettnerMD 

Department of Internal

Medicine I

University Medical Center

Regensburg

Franz-Josef-Strauss-Allee 11

93042 Regensburg

Germany

Phone: +49/941/9447 003

Fax: +49/941/9447 004

Email: roland.buettner@klinik.uni-regensburg.de

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