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Reduction of Elevated Serum Retinol Binding Protein in Obese Children by Lifestyle Intervention: Association with Subclinical Inflammation

Nemours Children’s Clinic (P.B., A.A., V.F., D.G.) and Mayo Clinic College of Medicine (P.B.), Jacksonville, Florida 32207; and Division of Endocrinology, Diabetes, and Metabolism (T.E.G., B.B.K.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215

Address all correspondence and requests for reprints to: Prabhakaran Balagopal, Ph.D., Nemours Children’s Clinic, 807 Children’s Way, Jacksonville, Florida 32207. E-mail: bbalagop{at}nemours.org.

Context: Retinol binding protein (RBP4), secreted primarily from the liver and adipose tissues, was recently proposed as a link between obesity and insulin resistance. The role of RBP4 in pediatric obesity, its relationship with subclinical inflammation, and its response to lifestyle changes are not elucidated.

Objective: The objective of the study was to determine in children: 1) the status of RBP4 levels in lean vs. obese; 2) the relationship between RBP4 levels and subclinical inflammation; and 3) the effect of lifestyle-only intervention on RBP4 levels.

Design, Setting, and Patients: Lean and obese children (n = 21) matched for age (>14 yr to < 18 yr) and maturity stage (Tanner IV) were studied at baseline and with lifestyle intervention in obese subjects only (n = 15).

Intervention: Patients received 3 months of randomized and controlled physical activity-based lifestyle intervention.

Main Outcome Measure: RBP4 levels in children before and after intervention and the relationship between RBP4 and subclinical inflammation were measured.

Results: Higher RBP4 levels were found in the obese group vs. lean group (P = 0.005). RBP4 correlated with not only indices of obesity and insulin resistance but also inflammatory factors (r = 0.63 and 0.64 for C-reactive protein and IL-6, respectively, P < 0.01). Intervention reduced RBP4 levels by approximately 30% (P = 0.001), and RBP4 reduction was correlated with the magnitude of decrease in inflammatory factors (P = 0.01).

Conclusion: Alterations in serum RBP4 occur at an early age in the clinical course of obesity and appear to correlate with subclinical inflammation. Lifestyle intervention almost entirely reversed the raised RBP4 levels in obese children. Future studies should determine whether elevation of RBP4 is a direct trigger for the insulin resistance and subclinical inflammation implicated in the premature development of cardiovascular disease and diabetes.

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