Serum paraoxonase 1 activity is paradoxically maintained in non-alcoholic fatty liver disease despite low HDL cholesterol.

Non-alcoholic fatty liver disease (NAFLD) is featured by low HDL cholesterol, but activity of the HDL-associated anti-oxidative enzyme paraoxonase-1 (PON-1) remains unclear. To determine the association of PON-1 with suspected NAFLD, we measured serum enzyme activity in 7,622 participants of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort. Fatty Liver Index (FLI)≥60, a proxy of NAFLD, was present in 2,083 participants (27.3%), and coincided with increased prevalence of type 2 diabetes mellitus (T2D), metabolic syndrome (MetS), (central) obesity, elevated triglycerides and low HDL cholesterol (all P<0.001). In men and women combined, serum PON-1 activity did not vary according to elevated FLI (P=0.98), whereas in men with elevated FLI PON-1 activity was increased (P=0.016). In multivariable linear regression analyses (adjusted for age, sex, T2D, MetS, alcohol use and smoking), PON-1 activity was unexpectedly associated with elevated FLI (β=0.083, P<0.001). In a sensitivity analysis (n=5,126), which excluded subjects with positive cardiovascular history, impaired estimated glomerular filtration rate, elevated urinary albumin excretion and drug use, PON-1 activity was also independently associated with elevated FLI (β=0.045, P=0.017). These results indicate that PON-1 is paradoxically maintained and may even be increased in NAFLD, despite inverse associations with metabolic disorders and low HDL cholesterol.