Retinol binding protein 4 (RBP4) is primarily associated with adipose tissue mass in children

Objective. Retinol binding protein 4 (RBP4) is a novel adipocytokine that may link obesity and insulin resistance. We aimed to discriminate between primary and secondary associations of RBP4 with obesity and related disease. Design. We applied clinical and experimental approaches to investigate the association of RBP4 levels with normal development, obesity, metabolic and cardiovascular parameters in 68 lean and 61 obese children. Results. RBP4 significantly increased with age and pubertal development in healthy lean children. Obese children had significantly higher RBP4 levels compared with lean controls (30.5 +/- 1.4 vs. 26.3 +/- 1.1 mg/L, P < 0.05) and there was a clear association with BMI independent of age (r = 0.33, P < 0.0001). RBP4 levels correlated significantly with parameters of lipid and glucose metabolism, as well as cardiovascular parameters in univariate analyses. Multiple regression analyses confirmed the strong association of RBP4 with BMI z-score and age, while the association with most metabolic and cardiovascular parameters was abolished. To assess whether the association of RBP4 with obesity may be attributable to adipogenesis, we evaluated RBP4 expression and secretion during adipocyte differentiation using the human SGBS cell line. In preadipocytes, RBP4 mRNA expression was nearly undetectable but increased during differentiation up to approximately 1600-fold (P < 0.05). Likewise, RBP4 secretion was restricted to mature adipocytes, further indicating that RBP4 is strongly related to differentiation of adipocytes. Conclusion. RBP4 is a marker of adipose tissue mass and obesity already evident in children. The association of RBP4 with metabolic and cardiovascular sequelae of obesity appears to be secondary to the underlying relationship wtih body fat.