Reduction of Elevated Serum Retinol Binding Protein in Obese Children by Lifestyle Intervention: Association with Subclinical Inflammation
Prabhakaran Balagopal,
Timothy E. Graham,
Barbara B. Kahn,
Astride Altomare,
Vicky Funanage and
Donald George
Nemours Childrens 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 Childrens Clinic, 807 Childrens Way, Jacksonville, Florida 32207. E-mail: bbalagop{at}nemours.org.
Context: Retinol binding protein (RBP4), secreted primarilyfrom the liver and adipose tissues, was recently proposed asa link between obesity and insulin resistance. The role of RBP4in 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 relationshipbetween RBP4 levels and subclinical inflammation; and 3) theeffect 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 interventionin obese subjects only (n = 15).
Intervention: Patients received 3 months of randomized and controlledphysical activity-based lifestyle intervention.
Main Outcome Measure: RBP4 levels in children before and afterintervention and the relationship between RBP4 and subclinicalinflammation were measured.
Results: Higher RBP4 levels were found in the obese group vs.lean group (P = 0.005). RBP4 correlated with not only indicesof 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 approximately30% (P = 0.001), and RBP4 reduction was correlated with themagnitude of decrease in inflammatory factors (P = 0.01).
Conclusion: Alterations in serum RBP4 occur at an early agein the clinical course of obesity and appear to correlate withsubclinical inflammation. Lifestyle intervention almost entirelyreversed the raised RBP4 levels in obese children. Future studiesshould determine whether elevation of RBP4 is a direct triggerfor the insulin resistance and subclinical inflammation implicatedin the premature development of cardiovascular disease and diabetes.
This article has been cited by other articles:
C. L. Roth and T. Reinehr Roles of Gastrointestinal and Adipose Tissue Peptides in Childhood Obesity and Changes After Weight Loss Due to Lifestyle Intervention
Arch Pediatr Adolesc Med,
February 1, 2010;
164(2):
131 - 138.
[Abstract][Full Text][PDF]
D.-C. Manolescu, A. Sima, and P. V. Bhat All-trans Retinoic Acid Lowers Serum Retinol-Binding Protein 4 Concentrations and Increases Insulin Sensitivity in Diabetic Mice
J. Nutr.,
February 1, 2010;
140(2):
311 - 316.
[Abstract][Full Text][PDF]
P. Szodoray, I. F. Horvath, G. Papp, S. Barath, E. Gyimesi, L. Csathy, J. Kappelmayer, S. Sipka, A. K. Duttaroy, B. Nakken, et al. The immunoregulatory role of vitamins A, D and E in patients with primary Sjogren's syndrome
Rheumatology,
February 1, 2010;
49(2):
211 - 217.
[Abstract][Full Text][PDF]
M. Jourdan, A. Jaleel, H. Karakelides, G. C. Ford, B. B. Kahn, and K. S. Nair Impact of Type 1 Diabetes and Insulin Treatment on Plasma Levels and Fractional Synthesis Rate of Retinol-Binding Protein 4
J. Clin. Endocrinol. Metab.,
December 1, 2009;
94(12):
5125 - 5130.
[Abstract][Full Text][PDF]
Z. Yu, X. Ye, J. Wang, Q. Qi, O. H. Franco, K. L. Rennie, A. Pan, H. Li, Y. Liu, F. B. Hu, et al. Associations of Physical Activity With Inflammatory Factors, Adipocytokines, and Metabolic Syndrome in Middle-Aged and Older Chinese People
Circulation,
June 16, 2009;
119(23):
2969 - 2977.
[Abstract][Full Text][PDF]
E. Ingelsson and L. Lind Circulating Retinol-Binding Protein 4 and Subclinical Cardiovascular Disease in the Elderly
Diabetes Care,
April 1, 2009;
32(4):
733 - 735.
[Abstract][Full Text][PDF]
H. Wu, L. Wei, Y. Bao, J. Lu, P. Huang, Y. Liu, W. Jia, and K. Xiang Fenofibrate reduces serum retinol-binding protein-4 by suppressing its expression in adipose tissue
Am J Physiol Endocrinol Metab,
April 1, 2009;
296(4):
E628 - E634.
[Abstract][Full Text][PDF]
A. O. Chavez, D. K. Coletta, S. Kamath, D. T. Cromack, A. Monroy, F. Folli, R. A. DeFronzo, and D. Tripathy Retinol-binding protein 4 is associated with impaired glucose tolerance but not with whole body or hepatic insulin resistance in Mexican Americans
Am J Physiol Endocrinol Metab,
April 1, 2009;
296(4):
E758 - E764.
[Abstract][Full Text][PDF]
A. Motani, Z. Wang, M. Conn, K. Siegler, Y. Zhang, Q. Liu, S. Johnstone, H. Xu, S. Thibault, Y. Wang, et al. Identification and Characterization of a Non-retinoid Ligand for Retinol-binding Protein 4 Which Lowers Serum Retinol-binding Protein 4 Levels in Vivo
J. Biol. Chem.,
March 20, 2009;
284(12):
7673 - 7680.
[Abstract][Full Text][PDF]
Z. Mallat, T. Simon, J. Benessiano, K. Clement, S. Taleb, N. J. Wareham, R. Luben, K.-T. Khaw, A. Tedgui, and S. M. Boekholdt Retinol-Binding Protein 4 and Prediction of Incident Coronary Events in Healthy Men and Women
J. Clin. Endocrinol. Metab.,
January 1, 2009;
94(1):
255 - 260.
[Abstract][Full Text][PDF]
R. Ribel-Madsen, M. Friedrichsen, A. Vaag, and P. Poulsen Retinol-Binding Protein 4 in Twins: Regulatory Mechanisms and Impact of Circulating and Tissue Expression Levels on Insulin Secretion and Action
Diabetes,
January 1, 2009;
58(1):
54 - 60.
[Abstract][Full Text][PDF]
N. Stefan, K. Kantartzis, and H.-U. Haring Causes and Metabolic Consequences of Fatty Liver
Endocr. Rev.,
December 1, 2008;
29(7):
939 - 960.
[Abstract][Full Text][PDF]
J. P. Mills, H. C. Furr, and S. A. Tanumihardjo Retinol to Retinol-Binding Protein (RBP) Is Low in Obese Adults due to Elevated apo-RBP
Exp Biol Med,
October 1, 2008;
233(10):
1255 - 1261.
[Abstract][Full Text][PDF]
S. H. Choi, S. H. Kwak, B.-S. Youn, S. Lim, Y. J. Park, H. Lee, N. Lee, Y. M. Cho, H. K. Lee, Y.-B. Kim, et al. High Plasma Retinol Binding Protein-4 and Low Plasma Adiponectin Concentrations Are Associated with Severity of Glucose Intolerance in Women with Previous Gestational Diabetes Mellitus
J. Clin. Endocrinol. Metab.,
August 1, 2008;
93(8):
3142 - 3148.
[Abstract][Full Text][PDF]
T. M. Barber, M. Hazell, C. Christodoulides, S. J. Golding, C. Alvey, K. Burling, A. Vidal-Puig, N. P. Groome, J. A. H. Wass, S. Franks, et al. Serum Levels of Retinol-Binding Protein 4 and Adiponectin in Women with Polycystic Ovary Syndrome: Associations with Visceral Fat But No Evidence for Fat Mass-Independent Effects on Pathogenesis in This Condition
J. Clin. Endocrinol. Metab.,
July 1, 2008;
93(7):
2859 - 2865.
[Abstract][Full Text][PDF]
C. Kanaka-Gantenbein, A. Margeli, P. Pervanidou, S. Sakka, G. Mastorakos, G. P. Chrousos, and I. Papassotiriou Retinol-Binding Protein 4 and Lipocalin-2 in Childhood and Adolescent Obesity: When Children Are Not Just "Small Adults"
Clin. Chem.,
July 1, 2008;
54(7):
1176 - 1182.
[Abstract][Full Text][PDF]
T. Reinehr, B. Stoffel-Wagner, and C. L. Roth Retinol-Binding Protein 4 and Its Relation to Insulin Resistance in Obese Children before and after Weight Loss
J. Clin. Endocrinol. Metab.,
June 1, 2008;
93(6):
2287 - 2293.
[Abstract][Full Text][PDF]
S. de Ferranti and D. Mozaffarian The Perfect Storm: Obesity, Adipocyte Dysfunction, and Metabolic Consequences
Clin. Chem.,
June 1, 2008;
54(6):
945 - 955.
[Abstract][Full Text][PDF]
M. Mohlig, M. O Weickert, E. Ghadamgahi, A. M Arafat, J. Spranger, A. F H Pfeiffer, and C. Schofl Retinol-binding protein 4 is associated with insulin resistance, but appears unsuited for metabolic screening in women with polycystic ovary syndrome.
Eur. J. Endocrinol.,
April 1, 2008;
158(4):
517 - 523.
[Abstract][Full Text][PDF]
N. Mody, T. E. Graham, Y. Tsuji, Q. Yang, and B. B. Kahn Decreased clearance of serum retinol-binding protein and elevated levels of transthyretin in insulin-resistant ob/ob mice
Am J Physiol Endocrinol Metab,
April 1, 2008;
294(4):
E785 - E793.
[Abstract][Full Text][PDF]
Q. Qi, Z. Yu, X. Ye, F. Zhao, P. Huang, F. B. Hu, O. H. Franco, J. Wang, H. Li, Y. Liu, et al. Elevated Retinol-Binding Protein 4 Levels Are Associated with Metabolic Syndrome in Chinese People
J. Clin. Endocrinol. Metab.,
December 1, 2007;
92(12):
4827 - 4834.
[Abstract][Full Text][PDF]
I. Aeberli, R. Biebinger, R. Lehmann, D. l'Allemand, G. A. Spinas, and M. B. Zimmermann Serum Retinol-Binding Protein 4 Concentration and Its Ratio to Serum Retinol Are Associated with Obesity and Metabolic Syndrome Components in Children
J. Clin. Endocrinol. Metab.,
November 1, 2007;
92(11):
4359 - 4365.
[Abstract][Full Text][PDF]
M. Ziegelmeier, A. Bachmann, J. Seeger, U. Lossner, J. Kratzsch, M. Bluher, M. Stumvoll, and M. Fasshauer Serum Levels of Adipokine Retinol-Binding Protein-4 in Relation to Renal Function
Diabetes Care,
October 1, 2007;
30(10):
2588 - 2592.
[Abstract][Full Text][PDF]