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Review
. 2016 Jan 15;7(1):5-13.
doi: 10.3945/an.114.007955. Print 2016 Jan.

Choline, Its Potential Role in Nonalcoholic Fatty Liver Disease, and the Case for Human and Bacterial Genes

Jill L Sherriff  1 , Therese A O'Sullivan  2 , Catherine Properzi  2 , Josephine-Lee Oddo  2 , Leon A Adams  3
Affiliations
Review

Choline, Its Potential Role in Nonalcoholic Fatty Liver Disease, and the Case for Human and Bacterial Genes

Jill L Sherriff et al. Adv Nutr. .

Abstract

Our understanding of the impact of poor hepatic choline/phosphatidylcholine availability in promoting the steatosis characteristic of human nonalcoholic fatty liver disease (NAFLD) has recently advanced and possibly relates to phosphatidylcholine/phosphatidylethanolamine concentrations in various, membranes as well as cholesterol dysregulation. A role for choline/phosphatidylcholine availability in the progression of NAFLD to liver injury and serious hepatic consequences in some individuals requires further elucidation. There are many reasons for poor choline/phosphatidylcholine availability in the liver, including low intake, estrogen status, and genetic polymorphisms affecting, in particular, the pathway for hepatic de novo phosphatidylcholine synthesis. In addition to free choline, phosphatidylcholine has been identified as a substrate for trimethylamine production by certain intestinal bacteria, thereby reducing host choline bioavailability and providing an additional link to the increased risk of cardiovascular disease faced by those with NAFLD. Thus human choline requirements are highly individualized and biomarkers of choline status derived from metabolomics studies are required to predict those at risk of NAFLD induced by choline deficiency and to provide a basis for human intervention trials.

Keywords: NAFLD; choline; liver diseases; microbiome; nonalcoholic steatosis; phosphatidylcholine.

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Conflict of interest statement

Author disclosures: JL Sherriff, TA O’Sullivan, C Properzi, J-L Oddo, and LA Adams, no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Choline metabolism, including the BHMT gene for betaine–homocysteine S-methyltransferase, the CHDH gene for choline dehydrogenase, the MTHFD1 gene for methylenetetrahydrofolate dehydrogenase 1, and the PEMT gene for phosphatidylethanolamine N-methyltransferase. B12, vitamin B-12; BHMT, betaine-homocysteine S-methyltransferase; CHDH, choline dehydrogenase; MTHFD1, methylenetetrahydrofolate dehydrogenase 1; PEMT, phosphatidylethanolamine N-methyltransferase; THF, tetrahydrofolate. Reproduced with permission from reference .
FIGURE 2
FIGURE 2
Uptake, anabolism, catabolism, and secretion of PC in the liver. LysoPC, lysophosphatidylcholine; MDR2, multiple drug–resistant protein 2; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PEMT, phosphatidylethanolamine N-methyltransferase; PS, phosphatidylserine; SM, sphingomyelin. Reproduced with permission from reference .
FIGURE 3
FIGURE 3
Two pathways generate phosphatidylcholine in the liver: the choline pathway and the phosphatidylethanolamine N-methylase pathway. AdoHcy, adenosylhomocysteine; AdoMet, S-adenosylmethionine; DG, diacylglycerol; PPi, pyrophosphate. Reproduced with permission from reference .
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