Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
Liver Int. 2019 Oct;39(10):1895-1905. doi: 10.1111/liv.14174. Epub 2019 Jul 8.
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.
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/m , 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.
Liver PC content was lower in those with NASH (P = 1.8 x 10 ) 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 (r = -0.047, P = 0.557). Serum PC and serum cholesterol levels correlated strongly (r = 0.866, P = 7.1 x 10 ), while liver PC content did not correlate with serum cholesterol (r = 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 ) and correlated with liver PC content (r = 0.265, P = 0.001).
Decreased liver PC content in individuals with the NASH is independent of PEMT V175M genotype and could be partly linked to decreased GNMT expression.
肝脏磷脂酰胆碱（PC）代谢的改变与非酒精性脂肪性肝病（NAFLD）的发病机制有关。尽管参与合成 PC 的磷酸乙醇胺 N-甲基转移酶（PEMT）酶的遗传变异与疾病有关，但将 PC 代谢与非酒精性脂肪性肝炎（NASH）发病机制联系起来的功能机制仍不清楚。
使用质子磁共振（NMR）光谱法测量了 169 名肥胖个体（年龄 46.6±10 岁，平均±SD，BMI 43.3±6kg/m ，男性 53 名，女性 116 名）的血清 PC 水平和肝脏 PC 含量，并对 NAFLD 进行组织学评估；其中 106 人具有明显的肝脏表型。所有受试者均进行 PEMT rs7946 基因分型，并分析 PEMT 和甘氨酸 N-甲基转移酶（GNMT）的肝脏 mRNA 表达。
NASH 患者的肝 PC 含量较低（P=1.8×10 ），而 NASH 患者与正常肝患者的血清 PC 水平无差异（P=0.591）。有趣的是，血清和肝脏 PC 之间没有相关性（r=0.047，P=0.557）。血清 PC 和血清胆固醇水平之间具有很强的相关性（r=0.866，P=7.1×10 ），而肝 PC 含量与血清胆固醇无相关性（r=0.065，P=0.413）。PEMT V175M 基因型或 PEMT 表达均不能解释肝 PC 含量与 NASH 之间的关联。相反，NASH 患者的肝 GNMT mRNA 表达降低（P=3.8×10 ），与肝 PC 含量相关（r=0.265，P=0.001）。
NASH 患者肝 PC 含量降低与 PEMT V175M 基因型无关，可能部分与 GNMT 表达降低有关。
