Cholesterol efflux capacity is impaired in subjects with an elevated Fatty Liver Index, a proxy of non-alcoholic fatty liver disease

• Published in: Atherosclerosis Vol. 277; pp. 21 - 27
• Main Authors: van den Berg, Eline H., Gruppen, Eke G., Ebtehaj, Sanam, Bakker, Stephan J.L., Tietge, Uwe J.F., Dullaart, Robin P.F.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.10.2018
• Subjects: Aged; Atherosclerosis - blood; Atherosclerosis - epidemiology; Biomarkers - blood; Blood Glucose - metabolism; C-Reactive Protein - metabolism; Cholesterol - blood; Cholesterol efflux capacity; Cholesterol, HDL - blood; Cross-Sectional Studies; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - epidemiology; Fatty Liver Index; Female; Foam Cells - metabolism; HDL cholesterol; hsCRP; Humans; Inflammation - blood; Inflammation - epidemiology; Inflammation Mediators - blood; Male; Metabolic syndrome; Metabolic Syndrome - blood; Metabolic Syndrome - diagnosis; Metabolic Syndrome - epidemiology; Middle Aged; Netherlands - epidemiology; Non-alcoholic fatty liver disease; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - diagnosis; Non-alcoholic Fatty Liver Disease - epidemiology; Prevalence; Risk Factors; THP-1 Cells; Type 2 diabetes mellitus; Netherlands; FLI; NAFLD; SR-BI; ALT; Type 2 diabetes mellitus; Metabolic syndrome; apoB; Fatty Liver Index; HDL; LDL; NCEP-ATP III; ATP-binding cassette transporter; BMI; CEC; dpm; eGFR; PBS; AST; Cholesterol efflux capacity; T2D; NASH; HDL cholesterol; CVD; MetS; ApoA-I; GGT; hsCRP; UAE; Non-alcoholic fatty liver disease; PREVEND; RPMI
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2018.07.028

Non-alcoholic fatty liver disease (NAFLD) parallels the obesity epidemic and associates with components of the metabolic syndrome (MetS). Cholesterol efflux capacity (CEC) represents a key metric of high density lipoprotein (HDL) function which may predict atherosclerotic cardiovascular disease (CVD). Here we assessed the relationship of CEC with NAFLD. CEC was determined from THP-1 macrophage foam cells towards apolipoprotein B-depleted plasma among 639 subjects (454 men; 36 subjects with type 2 diabetes mellitus (T2D); 226 with MetS), participating in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. A Fatty Liver Index (FLI) ≥ 60 was used as a proxy of NAFLD. 372 participants had a FLI ≥60, which coincided with an increased prevalence of T2D and MetS (p = 0.009 and p < 0.001), as well as with central obesity, higher systolic blood pressure, glucose, total cholesterol, triglycerides and high sensitivity C-reactive protein (hsCRP), and decreased HDL cholesterol (p < 0.001 for each). In multivariable linear regression analyses, CEC was inversely associated with an elevated FLI, when taking account of clinical covariates (fully adjusted model: β = −0.091, p = 0.043), and alternatively when taking account of systolic blood pressure, waist/hip ratio, glucose, HDL cholesterol, triglycerides and hsCRP (fully adjusted model: β = −0.103, p = 0.034). Impaired CEC is associated with NAFLD, as inferred from a FLI≥60, even when taking account of lower HDL cholesterol and enhanced low-grade chronic inflammation. Reduced CEC could contribute to accelerated CVD in NAFLD patients. •NAFLD is associated with elevations in apoB lipoproteins and low HDL-C.•Cholesterol efflux capacity (CEC) was measured in 639 subjects with suspected NAFLD.•CEC was impaired in subjects with suspected NAFLD, i.e. a Fatty Liver Index (FLI) ≥60.•CEC remained inversely associated with an elevated FLI independent of HDL-C.•NAFLD may contribute to impaired HDL function, even when taking account of HDL-C.