Serum retinol binding protein 4 is associated with visceral fat in human with nonalcoholic fatty liver disease without known diabetes: a cross-sectional study

Background: High serum Retinol Binding Protein 4 (RBP4) levels were associated with insulin-resistant states in humans. To determine which fat compartments are associated with elevated RBP4 levels in humans, we measured serum RBP4 and hepatic fat content (HFC), visceral (VFA) and subcutaneous abdominal fat area (SFA) in 106 subjects with non-alcoholic fatty liver disease (NAFLD) without known diabetes. Methods: 106 patients with NAFLD (M/F: 61/45, aged 47.44 +/- 14.16 years) were enrolled. Subjects with known diabetes, chronic virus hepatitis, and those with alcohol consumption >= 30 g/d in man and >= 20 g/d in woman were excluded. Anthropometrics and laboratory tests, including lipid profile, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (gamma-GT) were conducted. HFC, VFA and SFA were determined by CT scan. Serum RBP4 was detected by an enzyme immunoassay kit and validated by quantitative Western blotting. Results: Circulating RBP4 was negatively associated with high-density lipoprotein cholesterol (HDL-c) (r = -0.392, p < 0.001), but positively with waist-to-hip ratio (WHR) (r = 0.343, p = 0.001), triglyceride (r = 0.330, p = 0.002), VFA (r = 0.298, p = 0.027), systolic blood pressure (r = 0.247, p = 0.020), diastolic blood pressure (r = 0.241, p = 0.023), gamma-GT (r = 0.239, p = 0.034), waist circumference (r = 0.218, p = 0.040). Differently, serum RBP4 levels were not associated with HFC (r = 0.199, p = 0.071), SFA, age, BMI, total cholesterol, low-density lipoprotein cholesterol (LDL-c), ALT or AST (all p > 0.05). Multiple linear regression analysis revealed that RBP4 correlated independently with VFA (Standard beta = 0.357, p = 0.019) and HDL-c (Standard beta = -0.345, p = 0.023) in all subjects, HDL-c (Standard beta = -0.315, p = 0.040) in men, VFA/SFA in women (Standard beta = 0.471, p = 0.049), not with HFC. However, serum RBP4 was positively correlated with HFC when HFC below 6.34% (r = 0.574, p = 0.001). Conclusions: RBP4 could be a marker of abdominal obesity, however, the role of RBP4 in the pathogenesis of NAFLD is not sufficiently elucidated.