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Choline's role in maintaining liver function: new evidence for epigenetic mechanisms

Mehedint, Mihai G.; Zeisel, Steven H.

Current Opinion in Clinical Nutrition & Metabolic Care: May 2013 - Volume 16 - Issue 3 - p 339–345
doi: 10.1097/MCO.0b013e3283600d46
PAEDIATRICS: Edited by Berthold Koletzko and Raanan Shamir

Purpose of review: Humans eating diets low in choline develop fatty liver and liver damage. Rodents fed choline–methionine-deficient diets not only develop fatty liver, but also progress to develop fibrosis and hepatocarcinoma. This review focuses on the role of choline in liver function, with special emphasis on the epigenetic mechanisms of action.

Recent findings: Dietary intake of methyl donors like choline influences the methylation of DNA and histones, thereby altering the epigenetic regulation of gene expression. The liver is the major organ within which methylation reactions occur, and many of the hepatic genes involved in pathways for the development of fatty liver, hepatic fibrosis, and hepatocarcinomas are epigenetically regulated.

Summary: Dietary intake of choline varies over a three-fold range and many humans have genetic polymorphisms that increase their demand for choline. Choline is an important methyl donor needed for the generation of S-adenosylmethionine. Dietary choline intake is an important modifier of epigenetic marks on DNA and histones, and thereby modulates the gene expression in many of the pathways involved in liver function and dysfunction.

Nutrition Research Institute at Kannapolis, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

Correspondence to Steven H. Zeisel, MD, PhD, UNC-Chapel Hill Nutrition Research Institute, Department of Nutrition, UNC Gillings Global School of Public Health and School of Medicine, 500 Laureate Way, Kannapolis, NC 28081, USA. Tel: +1 704 250 5003; fax: +1 704 250 5001; e-mail: steven_zeisel@unc.edu

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