, Volume 43, Issue 3, pp 603–610 | Cite as

Changes in ghrelin and asymmetrical dimethylarginine in obese Mexican adolescents after six-month lifestyle intervention

  • Fengyang Huang
  • Blanca Estela del-Río-Navarro
  • José Alfredo Pérez Ontiveros
  • Eliseo Ruiz-Bedolla
  • Efraín Navarro-Olivos
  • Santiago Villafaña
  • Guadalupe Bravo
  • Enrique Hong
Original Article


The aim of this study was to evaluate the effect of a six-month lifestyle intervention on ghrelin and asymmetrical dimethylarginine (ADMA) in obese Mexican adolescents. A total of 65 obese Mexican adolescents aged 10–16 years completed a six-month lifestyle intervention. Anthropometric and biochemical parameters were assessed at baseline and at six months. Twenty normal-weight adolescents were also evaluated at baseline. Insulin resistance (IR) was determined by the homeostasis model assessment of IR (HOMA-IR). Ghrelin and ADMA were determined by enzyme-linked immunosorbent assay. Obese adolescents presented significantly higher triglycerides, cholesterol, glucose, insulin, HOMA-IR, and ADMA levels, while ghrelin was significantly lower. The lifestyle intervention led to a significant improvement in HOMA-IR, ghrelin, and ADMA in the whole studied obese subjects. ADMA and ghrelin levels were associated with BMI and IR components. According to the value of HOMA-IR, the obese subjects were divided into subjects with or without IR, no difference in ghrelin and ADMA was observed in these two subgroups. After intervention, the obese with IR showed increased ghrelin and decreased ADMA, while the obese without IR only showed improvement in ghrelin. The multiple linear regression analysis revealed that the changes of systolic blood pressure were the only predictor for the changes of ghrelin in the obese with IR. Our study demonstrated the increase of ADMA and the decrease of ghrelin in obese adolescents. Lifestyle intervention improved insulin resistance, decreased ADMA, and increased ghrelin in obese subjects with IR although no significant weight loss was observed.


Ghrelin Asymmetrical dimethylarginine Obese adolescents Lifestyle intervention 



We thank Emma Guadalupe Gazcón Morales, Daniel Chavez Vazquez, and Sergio Arturo Mavil Cortes for help with blood sample collection and laboratory measures. This work was supported by Grants (HIM/2007/008 and HIM/2008/007) from Hospital Infantíl de México Federico Gómez.

Conflict of interest

The authors report no conflicts of interest.


  1. 1.
    A.J. Van der Lely, M. Tschop, M.L. Heiman, E. Ghigo, Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr. Rev. 25, 426–457 (2004)PubMedCrossRefGoogle Scholar
  2. 2.
    M. Kojima, H. Hosoda, Y. Date, M. Nakazato, H. Matsuo, K. Kangawa, Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402, 656–660 (1999)PubMedCrossRefGoogle Scholar
  3. 3.
    P. Wiedmer, R. Nogueiras, F. Broglio, D. D’Alessio, M.H. Tschop, Ghrelin, obesity and diabetes. Nat. Clin. Pract. Endocrinol. Metab. 3, 705–712 (2007)PubMedCrossRefGoogle Scholar
  4. 4.
    M. Tschöp, C. Weyer, P.A. Tataranni, V. Devanarayan, E. Ravussin, M.L. Heiman, Circulating ghrelin levels are decreased in human obesity. Diabetes 50, 707–709 (2001)PubMedCrossRefGoogle Scholar
  5. 5.
    A. Ikezaki, H. Hosoda, K. Ito, S. Iwama, N. Miura, H. Matsuoka, C. Kondo, M. Kojima, K. Kangawa, S. Sugihara, Fasting plasma ghrelin levels are negatively correlated with insulin resistance and PAI-1, but not with leptin, in obese children and adolescents. Diabetes 51, 3408–3411 (2002)PubMedCrossRefGoogle Scholar
  6. 6.
    T. Shiiya, M. Nakazato, M. Mizuta, Y. Date, M.S. Mondal, M. Tanaka, S. Nozoe, H. Hosoda, K. Kangawa, S. Matsukura, Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J. Clin. Endocrinol. Metab. 87, 240–244 (2002)PubMedCrossRefGoogle Scholar
  7. 7.
    R.S. Ahima, Ghrelin—a new player in glucose homeostasis? Cell Metab. 3, 301–302 (2006)PubMedCrossRefGoogle Scholar
  8. 8.
    S. Bellone, N. Castellino, F. Broglio, A. Rapa, D. Vivenza, G. Radetti, J. Bellone, C. Gottero, E. Ghigo, G. Bona, Ghrelin secretion in childhood is refractory to the inhibiting effect of feeding. J. Clin. Endocrinol. Metab. 89, 1662–1665 (2004)PubMedCrossRefGoogle Scholar
  9. 9.
    K.M. Choi, J. Lee, K.W. Lee, J.A. Seo, J.H. Oh, S.G. Kim, D.S. Choi, S.H. Baik, The associations between plasma adiponectin, ghrelin levels, and cardiovascular risk factors. Eur. J. Endocrinol. 150, 715–718 (2004)PubMedCrossRefGoogle Scholar
  10. 10.
    L. Soriano-Guillen, V. Barrios, A. Campos-Barros, J. Argente, Ghrelin levels in obesity and anorexia nervosa: effect of weight reduction or recuperation. J. Pediatr. 144, 36–42 (2004)PubMedCrossRefGoogle Scholar
  11. 11.
    T. Reinehr, C.L. Roth, U. Alexy, M. Kersting, W. Kiess, W. Andler, Ghrelin levels before and after reduction of overweight due to a low fat high carbohydrate diet in obese children and adolescents. Int. J. Obes. 29, 362–368 (2005)CrossRefGoogle Scholar
  12. 12.
    D.G. Haider, K. Schindler, G. Prager, A. Bohdjalian, A. Luger, M. Wolzt, B. Ludvik, Serum retinol-binding protein-4 is reduced after weight loss in morbidly obese subjects. J. Clin. Endocrinol. Metab. 92, 1168–1171 (2007)PubMedCrossRefGoogle Scholar
  13. 13.
    D.E. Cummings, D.S. Weigle, R.S. Frayo, P.A. Breen, M.K. Ma, E.P. Dellinger, J.Q. Purnell, Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N. Engl. J. Med. 346, 1623–1630 (2002)PubMedCrossRefGoogle Scholar
  14. 14.
    T. Reinehr, G. de Sousa, L.R. Christian, Obestatin and ghrelin levels in obese children and adolescents before and after reduction of overweight. Clin. Endocrinol. 68, 304–310 (2008)Google Scholar
  15. 15.
    J.M. Garcia, D. Iyer, W.C.S. Posten, M. Marcelli, R. Reeves, J. Foreyt, A. Balasubramanyam, Rise of plasma ghrelin with weight loss is not sustained during weight maintenance. Obesity 14, 1716–1723 (2006)PubMedCrossRefGoogle Scholar
  16. 16.
    D.S. Weigle, D.E. Cummings, P.D. Newby, P.A. Breen, R.S. Frayo, C.C. Matthys, H.S. Callahan, J. Purnell, Roles of leptin and ghrelin in the loss of body weight caused by a low fat, high carbohydrate diet. J. Clin. Endocrinol. Metab. 88, 1577–1586 (2003)PubMedCrossRefGoogle Scholar
  17. 17.
    R.H. Böger, S.M. Bode-Böger, A. Szuba, P.S. Tsao, J.R. Chan, O. Tangphao, T.F. Blaschke, J.P. Cooke, Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation 98, 1842–1847 (1998)PubMedCrossRefGoogle Scholar
  18. 18.
    H. Matsuoka, S. Itoh, M. Kimoto, K. Kohno, O. Tamai, Y. Wada, H. Yasukawa, G. Iwami, S. Okuda, T. Imaizumi, Asymmetrical dimethylarginine, an endogenous nitric oxide synthase inhibitor, in experimental hypertension. Hypertension 29, 242–247 (1997)PubMedCrossRefGoogle Scholar
  19. 19.
    R.H. Böger, S.M. Bode-Böger, W. Thiele, W. Junker, K. Alexander, J.C. Frolich, Biochemical evidence for impaired nitric oxide synthesis in patients with peripheral arterial occlusive disease. Circulation 95, 2068–2074 (1997)PubMedCrossRefGoogle Scholar
  20. 20.
    F. Abbasi, T. Asagmi, J.P. Cooke, C. Lamendola, T. McLaughlin, G.M. Reaven, M. Stuehlinger, P.S. Tsao, Plasma concentrations of asymmetric dimethylarginine are increased in patients with type 2 diabetes mellitus. Am. J. Cardiol. 88, 1201–1203 (2001)PubMedCrossRefGoogle Scholar
  21. 21.
    C.D. Goonasekera, D.D. Rees, P. Woolar, Nitric oxide synthase inhibitors and hypertension in children and adolescents. J. Hypertens. 15, 901–909 (1997)PubMedCrossRefGoogle Scholar
  22. 22.
    C.D. Goonasekera, V. Shah, D.D. Rees, M.J. Dillon, Nitric oxide activity in childhood hypertension. Arch. Dis. Child. 77, 11–16 (1997)PubMedCrossRefGoogle Scholar
  23. 23.
    N. Nagaya, M. Kojima, M. Uematsu, Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am. J. Physiol. Regul. Integr. Comp. Physiol. 280, R1483–R1487 (2001)PubMedGoogle Scholar
  24. 24.
    R.J. Kuczmarski, C.L. Ogden, L.M. Grummer-Strawn, K.M. Flegal, S.S. Guo, R. Wei, Z. Mei, L.R. Curtin, A.F. Roche, C.L. Johnson, CDC growth charts: United States. Adv. Data 314, 1–28 (2000)PubMedGoogle Scholar
  25. 25.
    B. García-Cuartero, C. García-Lacalle, C. Jiménez-Lobo, A. González-Vergaz, C. Calvo-Rey, M.J. Alcázar-Villar, E. Díaz-Martínez, Indice HOMA y QUICKI, insulina y peptido C en ninos sanos. Puntos de corte de riesgo cardiovascular. An. Pediatr. (Barc) 66, 481–490 (2007)CrossRefGoogle Scholar
  26. 26.
    R.K. Golley, A.M. Magarey, L.A. Baur, K.S. Steinbeck, L.A. Daniels, Twelve-month effectiveness of a parent-family-focused weight-management program for prepubertal children: a randomized controlled trial. Pediatrics 119, 517–525 (2007)PubMedCrossRefGoogle Scholar
  27. 27.
    F.Y. Huang, B. Del-Río-Navarro, G. Toussaint Martínez de Castro, S. Torres-Alcántara, J.J.J. Siera-Monge, J.A. Pérez-Ontiveros, E. Navarro-Olivos, M. Figueroa-Barron, A. Reyes-Lopéz, S. Villafaña, E. Hong, Weight loss induced by 6-month lifestyle intervention improves early endothelial activation and fibrinolysis in obese adolescents. Child Care Health. Dev. 37, 377–384 (2011)PubMedCrossRefGoogle Scholar
  28. 28.
    C. Pedrosa, B.M.P.M. Oliveira, I. Albuquerque, C. Simões-Pereira, M.D. Vaz-de-Almeida, F. Correia, Metabolic syndrome, adipokines and ghrelin in overweight and obese schoolchildren: results of a 1-year lifestyle intervention programme. Eur. J. Pediatr. 170, 483–492 (2011)PubMedCrossRefGoogle Scholar
  29. 29.
    M.P. Bahíllo-Curieses, F. Hermoso-López, M.J. Martínez-Sopena, P. Cobreros-García, P. García-Saseta, M. Tríguez-García, J.M. Marugán-Miguelsanz, Prevalence of insulin resistance and impaired glucose tolerance in a sample of obese Spanish children and adolescents. Endocrine 41, 289–295 (2012)PubMedCrossRefGoogle Scholar
  30. 30.
    C. Gazzaruso, S. Giordanetti, A. La Manna, M. Celsa, E. De Amici, C. Turpini, A. Catona, P. Fratino, Weight loss after Swedish Adjustable Gastric Banding: relationships to insulin resistance and metabolic syndrome. Obes. Surg. 12, 841–845 (2002)PubMedCrossRefGoogle Scholar
  31. 31.
    L. Velázquez-López, E. González-Figueroa, P. Medina-Bravo, I. Pineda-del Aguila, L. Ávila-Jiménez, R. Ramos-Hernández, M. Klunder-Klunder, J. Escobedo-de la Peña, Low calorie and carbohydrate diet: to improve the cardiovascular risk indicators in overweight or obese adults with prediabetes. Endocrine (2012). doi: 10.1007/s12020-012-9775-z PubMedGoogle Scholar
  32. 32.
    P. Balagopal, S.S. Gidding, L.M. Buckloh, H.N. Yarandi, J.E. Sylvester, D.E. George, V.L. Funanage, Changes in circulating satiety hormones in obese children: a randomized controlled physical activity-based intervention study. Obesity 18, 1747–1753 (2010)PubMedCrossRefGoogle Scholar
  33. 33.
    R. Kelishadi, M. Hashemipour, N. Mohammadifard, H. Alikhassy, K. Adeli, Short- and long-term relationships of serum ghrelin with changes in body composition and the metabolic syndrome in prepubescent obese children following two different weight loss programmes. Clin. Endocrinol. 69, 721–729 (2008)CrossRefGoogle Scholar
  34. 34.
    A.C. Ellis, P. Chandler-Laney, K. Casazza, L.L. Goree, B.A. Gower, Effects of habitual diet on ethnic differences in serum total ghrelin. Endocrine (2012). doi: 10.1007/s12020-012-9667-2 PubMedGoogle Scholar
  35. 35.
    H.J. Leidy, J.K. Gardner, B.R. Frye, M.L. Snook, M.K. Schuchert, E.L. Richard, N.I. Williams, Circulating ghrelin is sensitive to changes in body weight during a diet and exercise program in normal-weight young women. J. Clin. Endocrinol. Metab. 89, 2659–2664 (2004)PubMedCrossRefGoogle Scholar
  36. 36.
    F. Bacha, S.A. Arslanian, Ghrelin suppression in overweight children: a manifestation of insulin resistance? J. Clin. Endocrinol. Metab. 90, 2725–2730 (2005)PubMedCrossRefGoogle Scholar
  37. 37.
    T. McLaughlin, F. Abbasi, C. Lamendola, R.S. Frayo, D.E. Cummings, Plasma ghrelin concentrations are decreased in insulin-resistant obese adults relative to equally obese insulin-sensitive controls. J. Clin. Endocrinol. Metab. 89, 1630–1635 (2004)PubMedCrossRefGoogle Scholar
  38. 38.
    R. Barazzoni, M. Zanetti, C. Ferreira, Relationships between desacylated and acylated ghrelin and insulin sensitivity in the metabolic syndrome. J. Clin. Endocrinol. Metab. 92, 3935–3940 (2007)PubMedCrossRefGoogle Scholar
  39. 39.
    H.J. Kim, S. Lee, T.W. Kim, Effects of exercise-induced weight loss on acylated and unacylated ghrelin in overweight children. Clin. Endocrinol. (Oxf) 68, 416–422 (2008)Google Scholar
  40. 40.
    H.-J. Gruber, C. Mayer, A. Meinitzer, G. Almer, R. Horejsi, R. Möller, S. Pilz, W. März, R. Gasser, M. Truschnig-Wilders, H. Mangge, Asymmetric dimethylarginine (ADMA) is tightly correlated with growth in juveniles without correlations to obesity related disorders. Exp. Clin. Endocrinol. Diabetes 116, 520–524 (2008)PubMedCrossRefGoogle Scholar
  41. 41.
    G. Rudofsky, E. Roeder, T. Merle, M. Hildebrand, P.P. Nawroth, C. Wolfrum, Weight loss improves endothelial function independently of ADMA reduction in severe obesity. Horm. Metab. Res. 43, 343–348 (2011)PubMedCrossRefGoogle Scholar
  42. 42.
    K. Krzyzanowska, F. Mittermayer, H.-P. Kopp, M. Wolzt, G. Schernthaner, Weight loss reduces circulating asymmetrical dimethylarginine concentrations in morbidly obese women. J. Clin. Endocrinol. Metab. 89, 6277–6281 (2004)PubMedCrossRefGoogle Scholar
  43. 43.
    T. McLaughlin, M. Stühlinger, C. Lamendola, F. Abbasi, J. Bialek, G.M. Reaven, P.S. Tsao, Plasma asymmetric dimethylarginine concentrations are elevated in obese insulin-resistant women and fall with weight loss. J. Clin. Endocrinol. Metab. 91, 1896–1900 (2006)PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Fengyang Huang
    • 1
  • Blanca Estela del-Río-Navarro
    • 2
  • José Alfredo Pérez Ontiveros
    • 1
  • Eliseo Ruiz-Bedolla
    • 3
  • Efraín Navarro-Olivos
    • 4
  • Santiago Villafaña
    • 5
  • Guadalupe Bravo
    • 6
  • Enrique Hong
    • 6
  1. 1.Department of Pharmacology and ToxicologyHospital Infántil de México Federico Gómez (HIMFG)Mexico CityMexico
  2. 2.Department of AllergyHospital Infántil de México Federico Gómez (HIMFG)Mexico CityMexico
  3. 3.Laboratory CenterHospital Infántil de México Federico Gómez (HIMFG)Mexico CityMexico
  4. 4.Department of Environmental HealthInstituto Nacional de Salud PúblicaCuernavacaMexico
  5. 5.Superior School of MedicineNational Polytechnic InstituteMexico CityMexico
  6. 6.Department of PharmacobiologyCentro de Investigación de Estudio Avanzados del Instituto Politécnico NacionalMexico CityMexico

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