Retinol-Binding Protein 4 and Lipocalin-2 in Childhood and Adolescent Obesity: When Children Are Not Just “Small Adults”

Abstract Background: Although there is much evidence regarding the physiologic and pathogenic roles of the newly described adipokines retinol-binding protein 4 (RBP4) and lipocalin-2 as potential promoters of insulin resistance in obese adults, relatively little information exists regarding their roles in obese children. Methods: We investigated the circulating concentrations of RBP4 and lipocalin-2 in 80 obese girls (ages 9– 15 years) and their relationships with high-sensitivity C-reactive protein (hs-CRP) and the adipokines leptin and adiponectin. We divided participants by their body mass index standard deviation scores (BMI SDSs) into 4 groups of 20 girls each: overweight [mean BMI SDS (SD), 1.8 (0.4)], obese [2.2 (0.4)], morbidly obese [3.6 (0.4)], and lean controls [−0.11 (0.4)]. We measured plasma-soluble RBP4, the RBP4-binding protein transthyretin, lipocalin-2, hs-CRP, leptin, and adiponectin and calculated the homeostatic assessment model (HOMA) index from fasting glucose and insulin concentrations. Results: Unexpectedly, plasma RBP4 and lipocalin-2 concentrations were correlated negatively with BMI SDS values (P = 0.005, and P < 0.03, respectively). These results were different from those of adults and were not correlated with the HOMA index. In contrast, hs-CRP and leptin concentrations were positively correlated with BMI SDS values (P < 0.0001, and P < 0.00001, respectively), as expected, whereas the adiponectin concentration was negatively correlated (P = 0.008). Conclusions: Although the correlations of leptin, adiponectin, and hs-CRP concentrations with BMI in children are similar to those of adults, the correlations of RBP4 and lipocalin-2 with BMI in children are the inverse of those observed in adults. Thus, although systemic inflammation and mild insulin resistance are present in childhood obesity, RBP4 and lipocalin-2 concentrations are not increased in children as they are in obese adults with long-standing severe insulin resistance and type 2 diabetes.