Obesity Surgery

, Volume 20, Issue 9, pp 1258–1264 | Cite as

Association of Retinol-Binding Protein-4 (RBP4) with Lipid Parameters in Obese Women

  • Montserrat BrochEmail author
  • José Manuel Gómez
  • Ma Teresa Auguet
  • Nuria Vilarrasa
  • Rosa Pastor
  • Iñaki Elio
  • Montserrat Olona
  • Antonio García-España
  • Cristóbal Richart
Clinical Research



Although the adipokine retinol-binding protein-4 (RBP4) has been implicated in the development of obesity-related insulin resistance, its role in human obesity is still unclear. Our objectives were to find out the effect on RBP4 systemic levels of a weight loss induced by gastric bypass surgery and to analyze RBP4 relationships with insulin resistance, parameters of body composition, lipid metabolism, and inflammation.


Sixty-three obese women were analyzed before and 12 months after surgery of systemic concentrations of RBP4, fasting glucose, insulin, lipid profile molecules, and inflammation-related proteins (C-reactive protein, tumor necrosis factor-alpha receptors 1 and 2, interleukin-18, and adiponectin), and waist and hip circumference measurements, body mass index calculation, and insulin resistance index by homeostasis model assessment were also made.


We found that RBP4 levels were lower after weight reduction by gastric bypass surgery (p < 0.0001). We found RBP4 associated with triglycerides before (β = 0.37, p = 0.02) and after surgery (β = 0.59, p < 0.0001) and negatively with weight loss after surgery (β = −0.37, p = 0.003). When expressed as a percentage of change, the decrease of RBP4 was related to the reduction in the levels of triglycerides and with the increase in HDL-cholesterol (β = 0.73, p = 0.02 and β = 0.62, p = 0.04, respectively). Others parameters analyzed, including inflammatory markers, were not related to RBP4.


This study shows that, in obese women and after a substantial weight loss due to bariatric surgery, RBP4 was related to weight status and lipid parameters rather than to insulin sensitivity or inflammatory markers.


Obesity Gastric bypass surgery Weight reduction Adipokines Triglycerides HDL-cholesterol Insulin resistance 



We thank all the women who participated in the study. This work was supported by research grants SAF2005-00413 and SAF2008-02278 (both to C.R.) from the Spanish Ministry of Science and Innovation (co-financed by FEDER) and by the “Fundación Biociencia”.

Conflict of interest statement

All the authors declare that they have no commercial conflicts of interest.


  1. 1.
    Jensen MD. Role of body fat distribution and the metabolic complications of obesity. J Clin Endocrinol Metab. 2008;93:S57–63.CrossRefPubMedGoogle Scholar
  2. 2.
    Rasouli N, Kern PA. Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab. 2008;93:S64–73.CrossRefPubMedGoogle Scholar
  3. 3.
    Kloting N, Graham TE, Berndt J, et al. Serum retinol-binding protein is more highly expressed in visceral than in subcutaneous adipose tissue and is a marker of intra-abdominal fat mass. Cell Metabolism. 2007;6:79–87.CrossRefPubMedGoogle Scholar
  4. 4.
    Yang Q, Graham TE, Mody N, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature. 2005;436:356–62.CrossRefPubMedGoogle Scholar
  5. 5.
    Takashima N, Tomoike H, Iwai N. Retinol-binding protein 4 and insulin resistance. N Engl J Med. 2006;355:1392–5.CrossRefPubMedGoogle Scholar
  6. 6.
    Stefan N, Hennige AM, Staiger H, et al. High circulating retinol-binding protein 4 is associated with elevated liver fat but not with total, subcutaneous, visceral, or intramyocellular fat in humans. Diabetes Care. 2007;30:1173–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Broch M, Vendrell J, Ricart W, et al. Circulating retinol-binding protein-4, insulin sensitivity, insulin secretion, and insulin disposition index in obese and non-obese subjects. Diabetes Care. 2007;30:1802–6.CrossRefPubMedGoogle Scholar
  8. 8.
    Von Eynatten M, Lepper PM, Liu D, et al. Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease. Diabetologia. 2007;50:1930–7.CrossRefGoogle Scholar
  9. 9.
    Qi Q, Yu Z, Ye X, et al. Elevated retinol-binding protein 4 levels are associated with metabolic syndrome in Chinese people. J Clin Endocrinol Metab. 2007;92:4827–34.CrossRefPubMedGoogle Scholar
  10. 10.
    Haider DG, Schindler K, Prager G, et al. Serum retinol-binding protein-4 is reduced after weight loss in morbidly obese subjects. J Clin Endocrin Metab. 2007;92:1168–71.CrossRefGoogle Scholar
  11. 11.
    Gomez-Ambrosi J, Rodriguez A, Catalán V, et al. Serum retinol-binding protein 4 is not increased in obesity or obesity-associated type 2 diabetes mellitus, but is reduced after relevant reductions in body fat following gastric bypass. Clin Endocrinol. 2008;69:208–15.CrossRefGoogle Scholar
  12. 12.
    Balagopal P, Graham TE, Kahn BB, et al. Reduction of elevated serum retinol binding protein (RBP4) in obese children by lifestyle intervention: association with sub-clinical inflammation. J Clin Endocrinol Metab. 2007;92:1971–4.CrossRefPubMedGoogle Scholar
  13. 13.
    Vitkota M, Klimcakova E, Kovacikova M, et al. Plasma levels and adipose tissue messenger ribonucleic acid expression of retinol-binding protein 4 are reduced during calorie restriction in obese subjects but are not related to diet-induced changes in insulin sensitivity. J Clin Endocrinol Metab. 2007;92:2330–5.CrossRefGoogle Scholar
  14. 14.
    Ng TW, Watts GF, Barret PH, et al. Effect of weight loss on LDL and HDL kinetics in the metabolic syndrome. Diabetes Care. 2007;30:2945–50.CrossRefPubMedGoogle Scholar
  15. 15.
    Lee JW, Lee HR, Shim JY, et al. Abdominal visceral fat reduction is associated with favorable changes of retinol binding protein-4 in nondiabetic subjects. Endocr J. 2008;55:811–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Reinehr T, Stoffel-Wagner B, Roth CL. Retinol-binding protein 4 and its relation to insulin resistance in obese children before and after weight loss. J Clin Endocrinol Metab. 2008;93:2287–93.CrossRefPubMedGoogle Scholar
  17. 17.
    Janke J, Engeli S, Boschmann M, et al. Retinol-binding protein in human obesity. Diabetes. 2006;55:2805–10.CrossRefPubMedGoogle Scholar
  18. 18.
    Yang RZ, Lee MJ, Hu H. Retinol binding protein 4: serum concentrations, adipose secretion, and its relationship to obesity. Diabetes. 2006;55:87A. Abstract.Google Scholar
  19. 19.
    Capella RF, Capella JF. Reducing early technical complications in gastric by-pass surgery. Obes Surg. 1997;7:149–57.CrossRefPubMedGoogle Scholar
  20. 20.
    Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabetic Med. 1998;15:539–53.CrossRefPubMedGoogle Scholar
  21. 21.
    Friedewald WT, Levi RI, Fredrickson DS. Estimation of the concentration of low density lipoprotein cholesterol in plasma without use of the ultracentrifuge. Clin Chem. 1972;18:499–502.PubMedGoogle Scholar
  22. 22.
    Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Fernández-Real JM, Molina A, Broch M, et al. Tumor necrosis factor system activity is associated with insulin resistance and dyslipemia in myotonic dystrophy. Diabetes. 1999;48:1108–12.CrossRefPubMedGoogle Scholar
  24. 24.
    Ross R, Janiszewski PM. Is weight loss the optimal target for obesity-related cardiovascular disease risk reduction? Can J Cardiol. 2008;24:25D–31D.PubMedGoogle Scholar
  25. 25.
    Cho YM, Youn BS, Lee H, et al. Plasma retinol-binding protein-4 concentrations are elevated in human subjects with impaired glucose tolerance and type 2 diabetes. Diabetes Care. 2006;29:2457–61.CrossRefPubMedGoogle Scholar
  26. 26.
    Gavi S, Stuart LM, Kelly P, et al. Retinol-binding protein 4 is associated with insulin resistance and body fat distribution in nonobese subjects without type 2 diabetes. J Clin Endocrinol Metab. 2007;92:1886–90.CrossRefPubMedGoogle Scholar
  27. 27.
    Giannessi D, Maltinti M, Del Ry S. Adiponectin circulating levels: a new emerging biomarker of cardiovascular risk. Pharmacol Res. 2007;56:459–67.CrossRefPubMedGoogle Scholar
  28. 28.
    Ghraham TE, Wason CJ, Blüher M, et al. Shortcomings in methodology complicate measurements of serum retinol binding protein (RBP4) in insulin-resistant human subjects. Diabetologia. 2007;50:814–23.CrossRefGoogle Scholar
  29. 29.
    Antuna-Puente B, Faraj M, Karelis AD, et al. HOMA or QUICKI: is it useful to test the reproducibility of formulas? Diabetes Metab. 2008;34:294–6.CrossRefPubMedGoogle Scholar
  30. 30.
    Munkhtulga L, Nakayama K, Utsumi N, et al. Identification of a 409 regulatory SNP in the retinol binding protein 4 gene associated with type 2 diabetes in Mongolia. Hum Genet. 2007;120:879–88.CrossRefPubMedGoogle Scholar
  31. 31.
    Craig RL, Chu WS, Elbein SC. Retinol binding protein 4 as a candidate gene for type 2 diabetes and prediabetic intermediate traits. Mol Genet Metab. 2007;90:338–44.CrossRefPubMedGoogle Scholar
  32. 32.
    Kovacs P, Geyer M, Berndt J, et al. Effects of genetic variation in the human retinol binding protein-4 gene (RBP4) on insulin resistance and fat depot-specific mRNA expression. Diabetes. 2007;56:3095–100.CrossRefPubMedGoogle Scholar
  33. 33.
    van Hoek M, Dehghan A, Zillikens MC, et al. An RBP4 promoter polymorphism increases risk of type 2 diabetes. Diabetologia. 2008;51:1423–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Ribel-Madsen R, Friedrichsen M, Vaag A, et al. Retinol-binding protein 4 in twins: regulatory mechanisms and impact of circulating and tissue expression levels on insulin secretion and action. Diabetes. 2009;58:54–60.CrossRefPubMedGoogle Scholar
  35. 35.
    Gerber LE, Erdman JW. Retinoic acid and hipertriglyceridemia. Ann N Y Acad Sci. 1981;359:391–2.CrossRefPubMedGoogle Scholar
  36. 36.
    Thuren T. Hepatic lipase and HDL metabolism. Curr Opin Lipidol. 2000;11:277–83.CrossRefPubMedGoogle Scholar
  37. 37.
    Shea JL, Loredo-Osti CL, Sun G. Association of RBP4 gene variants and serum HDL cholesterol levels in the Newfoundland population. Obesity. 2009;5:398–403.Google Scholar
  38. 38.
    Wu Y, Li H, Loos RJ, et al. RBP4 variants are significantly associated with plasma RBP4 levels and hypertriglyceridemia risk in Chinese Hans. J Lipid Res. 2009;50:1479–86.CrossRefPubMedGoogle Scholar
  39. 39.
    Broch M, Auguet MT, Ramírez R, et al. Parallel downregulation of retinol-binding protein-4 and adiponectin expression in subcutaneous adipose tissue of non-morbidly obese subjects. Eur J Endocrinol. 2009;161:87–94.CrossRefPubMedGoogle Scholar
  40. 40.
    Soprano DR, Soprano KJ, Goodman DS. Retinol-binding protein messenger RNA levels in the liver and in extrahepatic tissues of the rat. J Lipid Res. 1986;27:166–71.PubMedGoogle Scholar
  41. 41.
    Blaner WS. Retinol-binding protein: the serum transport protein for vitamin A. Endocr Rev. 1989;10:308–16.CrossRefPubMedGoogle Scholar
  42. 42.
    Suhara A, Kato M, Kanai M. Ultrastructural localization of plasma retinol-binding protein in rat liver. J Lipid Res. 1990;31:1669–81.PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2010

Authors and Affiliations

  • Montserrat Broch
    • 1
    • 6
    • 7
    Email author
  • José Manuel Gómez
    • 2
  • Ma Teresa Auguet
    • 1
    • 3
    • 6
  • Nuria Vilarrasa
    • 2
  • Rosa Pastor
    • 4
  • Iñaki Elio
    • 2
  • Montserrat Olona
    • 5
  • Antonio García-España
    • 6
  • Cristóbal Richart
    • 1
    • 3
    • 6
  1. 1.CIBER (CB06/03) Fisiopatologia de la Obesidad y NutriciónInstituto de Salud Carlos IIIMadridSpain
  2. 2.Endocrinology and Diabetes UnitHospital Universitari de BellvitgeBarcelonaSpain
  3. 3.Internal MedicineHospital Universitari de Tarragona Joan XXIIITarragonaSpain
  4. 4.Hormonal LaboratoryHospital Universitari de Tarragona Joan XXIIITarragonaSpain
  5. 5.Epidemiology and StatisticsHospital Universitari de Tarragona Joan XXIIITarragonaSpain
  6. 6.Institut d’Investigació Sanitaria Pere VirgiliUniversitat Rovira i VirgiliTarragonaSpain
  7. 7.Research UnitHospital Universitari de Tarragona Joan XXIIITarragonaSpain

Personalised recommendations