Total liver phosphatidylcholine content associates with non-alcoholic steatohepatitis and glycine N-methyltransferase expression.
Liver Int
; 39(10): 1895-1905, 2019 10.
Article
en En
| MEDLINE
| ID: mdl-31199045
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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Fosfatidilcolinas
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Glicina N-Metiltransferasa
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Fosfatidiletanolamina N-Metiltransferasa
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Enfermedad del Hígado Graso no Alcohólico
Tipo de estudio:
Risk_factors_studies
Límite:
Adult
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Liver Int
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Finlandia