Plasma lecithin:cholesterol acyltransferase and phospholipid transfer protein activity independently associate with nonalcoholic fatty liver disease

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent condition which contributes to atherogenic apolipoprotein B dyslipoproteinemias. Lecithin:cholesterol acyltransferase (LCAT) and phospholipid transfer protein (PLTP) are both synthesized by the liver and are important in lipid metabolism. Here, we interrogated the impact of NAFLD on plasma LCAT and PLTP activities. METHODS: Plasma LCAT activity (exogenous substrate assay) and PLTP activity (phospholipid vesicles-HDL assay) were determined in 348 subjects (279 men; 81 subjects with type 2 diabetes (T2DM); 123 with metabolic syndrome (MetS)). A Fatty Liver Index (FLI) ≥60 was used as a proxy of NAFLD. Insulin resistance was determined by homoeostasis model assessment (HOMA-IR). RESULTS: A total of 147 participants had an FLI ≥60 coinciding with T2DM and MetS (P < 0.001 for each). Plasma LCAT activity and PLTP activity were on average 12% and 5% higher, respectively, in subjects with an FLI ≥ 60 (P < 0.001 for each). In age- and sex-adjusted partial linear regression analysis, LCAT activity and PLTP activity were positively related to various obesity measures and HOMA-IR (P < 0.001 for each). In multivariable linear regression analyses adjusted for age and sex, LCAT activity was associated with an FLI ≥ 60 independent of T2DM and MetS, the waist/hip ratio, or HOMA-IR (β = 0.307 to 0.366, P < 0001 for all models). PLTP activity was also associated with an FLI ≥ 60 independent of these variables (β = 0.151 to 0223, P = 0.013 to 0.001). CONCLUSION: NAFLD, as inferred from an FLI≥60, confers higher plasma LCAT and to a lesser extent PLTP activity, even when taking account of T2DM, MetS, central obesity and insulin resistance.