4.1 Review

Choline metabolism provides novel insights into nonalcoholic fatty liver disease and its progression

Journal

CURRENT OPINION IN GASTROENTEROLOGY
Volume 28, Issue 2, Pages 159-165

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOG.0b013e32834e7b4b

Keywords

choline; metabolomics; microbiome; nonalcoholic fatty liver disease; single-nucleotide polymorphisms

Funding

  1. National Institutes of Health [R01 DK55865, P30DK056350]
  2. Balchem

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Purpose of review Choline is an essential nutrient and the liver is a central organ responsible for choline metabolism. Hepatosteatosis and liver cell death occur when humans are deprived of choline. In the last few years, there have been significant advances in our understanding of the mechanisms that influence choline requirements in humans and in our understanding of choline's effects on liver function. These advances are useful in elucidating why nonalcoholic fatty liver disease (NAFLD) occurs and progresses sometimes to hepatocarcinogenesis. Recent findings Humans eating low-choline diets develop fatty liver and liver damage. This dietary requirement for choline is modulated by estrogen and by single-nucleotide polymorphisms in specific genes of choline and folate metabolism. The spectrum of choline's effects on liver range from steatosis to development of hepatocarcinomas, and several mechanisms for these effects have been identified. They include abnormal phospholipid synthesis, defects in lipoprotein secretion, oxidative damage caused by mitochondrial dysfunction, and endoplasmic reticulum stress. Furthermore, the hepatic steatosis phenotype can be characterized more fully via metabolomic signatures and is influenced by the gut microbiome. Importantly, the intricate connection between liver function, one-carbon metabolism, and energy metabolism is just beginning to be elucidated. Summary Choline influences liver function, and the dietary requirement for this nutrient varies depending on an individual's genotype and estrogen status. Understanding these individual differences is important for gastroenterologists seeking to understand why some individuals develop NAFLD and others do not, and why some patients tolerate total parenteral nutrition and others develop liver dysfunction.

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