Arendt Bianca M, Ma David W L, Simons Brigitte, Noureldin Seham A, Therapondos George, Guindi Maha, Sherman Morris, Allard Johane P
a Department of Medicine, University Health Network, Toronto, ON M5G 2C4, Canada.
Appl Physiol Nutr Metab. 2013 Mar;38(3):334-40. doi: 10.1139/apnm-2012-0261. Epub 2012 Oct 15.
Nonalcoholic fatty liver disease (NAFLD) is associated with altered hepatic lipid composition. Animal studies suggest that the hepatic ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) contributes to steatogenesis and inflammation. This ratio may be influenced by dysregulation of the PE N-methyltransferase (PEMT) pathway or by a low-choline diet. Alterations in the liver may also influence lipid composition in circulation such as in erythrocytes, which therefore may have utility as a biomarker of hepatic disease. Currently, no study has assessed both liver and erythrocyte PC/PE ratios in NAFLD. The aim of this study was to compare the PC/PE ratio in the liver and erythrocytes of patients with simple steatosis (SS) or nonalcoholic steatohepatitis (NASH) with that of healthy controls. PC and PE were measured by mass spectrometry in 28 patients with biopsy-proven NAFLD (14 SS, 14 NASH) and 9 healthy living liver donors as controls. The hepatic PC/PE ratio was lower in SS patients (median [range]) (1.23 [0.27-3.40]) and NASH patients (1.29 [0.77-3.22]) compared with controls (3.14 [2.20-3.73]); both p < 0.001) but it was not different between SS and NASH. PC was lower and PE higher in the liver of SS patients compared with controls, whereas in NASH patients only PE was higher. The PC/PE ratio in erythrocytes was also lower in SS and NASH patients compared with controls because of lower PC in both patient groups. PE in erythrocytes was not different among the groups. In conclusion, NAFLD patients have a lower PC/PE ratio in the liver and erythrocytes than do healthy controls, which may play a role in the pathogenesis. The underlying mechanisms require further investigation.
非酒精性脂肪性肝病(NAFLD)与肝脏脂质成分改变有关。动物研究表明,磷脂酰胆碱(PC)与磷脂酰乙醇胺(PE)的肝脏比例会促进脂肪生成和炎症。该比例可能受PE N-甲基转移酶(PEMT)途径失调或低胆碱饮食的影响。肝脏的改变也可能影响循环中的脂质成分,如红细胞中的脂质成分,因此红细胞可能作为肝病的生物标志物。目前,尚无研究评估NAFLD患者肝脏和红细胞中的PC/PE比例。本研究的目的是比较单纯性脂肪变性(SS)或非酒精性脂肪性肝炎(NASH)患者与健康对照者肝脏和红细胞中的PC/PE比例。采用质谱法测量了28例经活检证实为NAFLD的患者(14例SS,14例NASH)和9例健康活体肝脏供体(作为对照)的PC和PE。与对照组(3.14 [2.20 - 3.73])相比,SS患者(中位数[范围])(1.23 [0.27 - 3.40])和NASH患者(1.29 [0.77 - 3.22])的肝脏PC/PE比例较低(两者p < 0.001),但SS和NASH之间无差异。与对照组相比,SS患者肝脏中的PC较低而PE较高,而在NASH患者中只有PE较高。由于两组患者的PC均较低,SS和NASH患者红细胞中的PC/PE比例也低于对照组。各组红细胞中的PE无差异。总之,NAFLD患者肝脏和红细胞中的PC/PE比例低于健康对照者,这可能在发病机制中起作用。其潜在机制需要进一步研究。