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Männistö, V, Kaminska, D, Kärjä, V, et al. Total liver phosphatidylcholine content associates with non‐alcoholic steatohepatitis and glycine N‐methyltransferase expression. Liver Int. 2019; 39: 1895– 1905. https://doi.org/10.1111/liv.14174

Total liver phosphatidylcholine content associates with non-alcoholic steatohepatitis and glycine N-methyltransferase expression

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Author: Männistö, Ville1; Kaminska, Dorota2; Kärjä, Vesa3;
Organizations: 1Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
2Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
3Department of Pathology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
4NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
5LC‐MS Metabolomics Center, Biocenter Kuopio, Kuopio, Finland
6Systems Epidemiology, Baker Heart and Diabetes Institute, Melbourne, Vic., Australia
7Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland
8Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK
9Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
10Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, The Alfred Hospital, Monash University, Melbourne, Vic., Australia
11Clinical Nutrition and Obesity Center, Kuopio University Hospital, Kuopio, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.8 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2019111943209
Language: English
Published: John Wiley & Sons, 2019
Publish Date: 2020-06-14
Description:

Abstract

Background & Aims: Alterations in liver phosphatidylcholine (PC) metabolism have been implicated in the pathogenesis of non‐alcoholic fatty liver disease (NAFLD). Although genetic variation in the phosphatidylethanolamine N‐methyltransferase (PEMT) enzyme synthesizing PC has been associated with disease, the functional mechanism linking PC metabolism to the pathogenesis of non‐alcoholic steatohepatitis (NASH) remains unclear.

Methods: Serum PC levels and liver PC contents were measured using proton nuclear magnetic resonance (NMR) spectroscopy in 169 obese individuals [age 46.6 ± 10 (mean ± SD) years, BMI 43.3 ± 6 kg/m2, 53 men and 116 women] with histological assessment of NAFLD; 106 of these had a distinct liver phenotype. All subjects were genotyped for PEMT rs7946 and liver mRNA expression of PEMT and glycine N‐methyltransferase (GNMT) was analysed.

Results: Liver PC content was lower in those with NASH (P = 1.8 x 10−6) while serum PC levels did not differ between individuals with NASH and normal liver (P = 0.591). Interestingly, serum and liver PC did not correlate (rs = −0.047, P = 0.557). Serum PC and serum cholesterol levels correlated strongly (rs = 0.866, P = 7.1 x 10−49), while liver PC content did not correlate with serum cholesterol (rs = 0.065, P = 0.413). Neither PEMT V175M genotype nor PEMT expression explained the association between liver PC content and NASH. Instead, liver GNMT mRNA expression was decreased in those with NASH (P = 3.8 x 10−4) and correlated with liver PC content (rs = 0.265, P = 0.001).

Conclusions: Decreased liver PC content in individuals with the NASH is independent of PEMT V175M genotype and could be partly linked to decreased GNMT expression.

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Series: Liver international
ISSN: 1478-3223
ISSN-E: 1478-3231
ISSN-L: 1478-3223
Volume: 39
Issue: 10
Pages: 1895 - 1905
DOI: 10.1111/liv.14174
OADOI: https://oadoi.org/10.1111/liv.14174
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
Subjects:
Glycine N-methyltransferase
Non-alcoholic fatty liver disease
Nonalcoholic steatohepatitis
Phosphatidylcholine
Phosphatidylethanolamine N-methyltransferase
Proton magnetic resonance spectroscopy
Article
Funding: Kuopio Obesity Surgery Study (PI JPI) was supported by the Finnish Diabetes Research Foundation, Kuopio University Hospital Project grant (NUDROBE), the Academy of Finland grant (Contract no. 120,979;138,006), the Finnish Cultural Foundation and the University of Eastern Finland Spearhead Funding. MAK is supported by a Senior Research Fellowship from the National Health and Medical Research Council (NHMRC) of Australia (APP1158958). He also works in a unit that is supported by the University of Bristol and UK Medical Research Council (MC_UU_12013/1). The Baker Institute is supported in part by the Victorian Government's Operational Infrastructure Support Program. VM was supported by the grant from the North Savo Regional Fund.
Copyright information: © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. This is the peer reviewed version of the following article: Männistö, V, Kaminska, D, Kärjä, V, et al. Total liver phosphatidylcholine content associates with non‐alcoholic steatohepatitis and glycine N‐methyltransferase expression. Liver Int. 2019; 39: 1895– 1905. https://doi.org/10.1111/liv.14174, which has been published in final form at https://doi.org/10.1111/liv.14174. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.