Elevated retinol binding protein 4 induces apolipoprotein B production and associates with hypertriglyceridemia

Abstract

Context and Objective: A high level of retinol binding protein 4 (RBP4) is reported to be associated with insulin resistance in humans. However, evidence from large-scale populations about the relationship between serum RBP4 and metabolic phenotypes is scarce. In the present study, we aimed to evaluate serum RBP4 distribution and its association with metabolic phenotypes among middle-aged and elderly Chinese. Design and Participants: Serum concentrations of RBP4 in a cross-sectional sample of 2780 Chinese population aged 50-70 years old in Guangzhou were measured by ELISA. Results: The mean of serum RBP4 concentration was 28.04 μg/mL for male and 37.76 μg/mL for female (P < .01), respectively. Circulating RBP4 was positively correlated with serum triglyceride and apolipoprotein B (apoB) concentrations. The odds ratio (OR) was substantially higher for hypertriglyceridemia (OR, 3.26; 95% confidence interval, 2.36-4.51) in the highest RBP4 quartile compared with those in the lowest quartile after multiple adjustment for confounders. Furthermore, serum RBP4 was significantly associated with fasting glucose, insulin levels, and homeostasis model assessment index-insulin resistance (HOMA-IR). Moreover, we showed that RBP4 enhanced microsomal triglyceride transfer protein (MTP) expression and activity via up-regulation of protein disulfide isomerase (PDI), suppressed low-density lipoprotein receptor (LDLR) expression, and impaired insulin-signaling pathway, leading to inductions in apoB secretion both in vitro and in vivo. Conclusions: Elevated circulating RBP4 concentrations were associated with higher risk of hyper-triglyceridemia by inducing the secretion of triglyceride-rich apoB-containing lipoproteins.