HDL-Mediated Cholesterol Efflux and Plasma Loading Capacities Are Altered in Subjects with Metabolically- but Not Genetically Driven Non-Alcoholic Fatty Liver Disease (NAFLD).

. Non-alcoholic fatty liver disease (NAFLD) increases the risk of atherosclerosis but this risk may differ between metabolically- vs. genetically-driven NAFLD. High-density lipoprotein (HDL)-mediated cholesterol efflux (CEC) and plasma loading capacity (CLC) are key factors in atherogenesis. . To test whether CEC and CLC differ between metabolically- vs. genetically-determined NAFLD. : CEC and CLC were measured in 19 patients with metabolic NAFLD and wild-type genotype (Group M), 10 patients with genetic NAFLD carrying M148M genotype (Group G), and 10 controls wild-types and without NAFLD. CEC and CLC were measured ex vivo by isotopic and fluorimetric techniques using cellular models. : Compared with Group G, Group M showed reduced total CEC (-18.6%; < 0.001) as well as that mediated by cholesterol transporters (-25.3% ABCA1; -16.3% ABCG1; -14.8% aqueous diffusion; all < 0.04). No difference in CEC was found between Group G and controls. The presence of metabolic syndrome further impaired ABCG1-mediated CEC in Group M. Group M had higher plasma-induced CLC than Group G and controls ( < 0.001). : Metabolically-, but not genetically-, driven NAFLD associates with dysfunctional HDL-meditated CEC and abnormal CLC. These data suggest that the mechanisms of anti-atherogenic protection in metabolic NAFLD are impaired.