Association of PAF and its metabolic enzymes with GGT and the Fatty Liver Index in healthy volunteers.

BACKGROUND Platelet-activating factor (PAF) is a lipid inflammatory mediator implicated in liver disease. Its main biosynthetic enzymes are cytidine diphosphate (CDP)-choline:1-alkyl-2-acetyl-sn-glycerol-cholinephosphotransferase (PAF-CPT) and acetyl-coenzyme A: lyso-PAF-acetyltransferases (Lyso-PAF-AT), while PAF acetylhydrolase (PAF-AH) and lipoprotein-associated phospholipase A2 (Lp-PLA2) degrade PAF. OBJECTIVE To explore the relation of PAF metabolism with liver diseases and non-alcoholic fatty liver disease, as reflected by the fatty liver index (FLI). METHODS In 106 healthy volunteers, PAF concentration, the activity of its metabolic enzymes, and gamma-glutamyl transferase (GGT) were measured in whole blood, leukocytes, and serum, respectively, and the FLI was calculated. Partial correlations and linear regression models were used. RESULTS In males, serum GGT activity was positively correlated with abdominal fat (as assessed by analysis of a manually defined region of interest in dual-energy X-ray absorptiometry), triacylglycerols, bound-PAF, and Lp-PLA2, while the FLI was positively correlated with Lp-PLA2 activity. In females, serum GGT activity was negatively associated with high-density lipoprotein cholesterol (HDL-C) (age-adjusted correlations, all p<0.05). Lp-PLA2 was a significant determinant of serum GGT activity in males after controlling for age, low-density lipoprotein cholesterol (LDL-C), and abdominal fat. The addition of bound-PAF in the model significantly increased the explained variance of serum GGT activity (total variance explanation 30%). CONCLUSION Bound-PAF and Lp-PLA2 activity predicted serum GGT activity, while Lp-PLA2 was also related to FLI. Our findings shed light on the metabolic pathways linking Lp-PLA2 to other atherosclerosis and/or oxidative markers, such as HDL-C, LDL-C, GGT, and FLI, and underline the important role of PAF.