Abstract
Previous studies conducted in adult obese patients have shown that glucocorticoid receptor and corticosteroid-binding globulin gene polymorphisms influence cortisol-driven obesity and metabolic parameters. We investigated the impact of these polymorphisms in prepubertal obese children that were thoroughly examined for hypothalamic–pituitary–adrenal axis activity and for metabolic and obesity parameters. Obese children carrier of the allele G of the BclI polymorphism within glucocorticoid receptor gene tend to present a higher percentage of fat mass as well as a decreased cortisol suppression after low-dose dexamethasone as found in adult studies. Additionally, these allele G carriers show a strong correlation between truncal fat mass distribution and cortisol response to a standardized lunch, whereas this correlation is weak in allele C carriers. No differences were found for obesity or metabolic parameters between genotypes at the corticosteroid-binding globulin locus. However, allele 90 carriers present increased 24-h free urinary cortisol. Overall, this study provides new data showing the influence of glucocorticoid receptor and corticosteroid-binding globulin genes in obesity and/or cortisol action in prepubertal obese children.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Barat P, Duclos M, Gatta B, Roger P, Mormède P, Moisan MP (2005) Corticosteroid binding globulin gene polymorphism influences cortisol driven fat distribution in obese women. Obesity Res 13:1485–1490
Barat P, Gayard-Cros M, Andrew R, Corcuff JB, Jouret B, Barthe N, Perez P, Germain C, Tauber M, Walker BR, Mormede P, Duclos M (2007) Truncal distribution of fat mass, metabolic profile and hypothalamic-pituitary adrenal axis activity in prepubertal obese children. J Pediatr 150(5):535–539
Bujalska IJ, Kumar S, Stewart PM (1997) Does central obesity reflect “Cushing’s disease of the omentum”? Lancet 349(9060):1210–1213
Cole TJ, Bellizzi MC, Flegal KM, Dietz WH (2000) Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 320(7244):1240–1243
Duclos M, Gatta B, Corcuff JB, Rashedi M, Pehourcq F, Roger P (2001) Fat distribution in obese women is associated with subtle alterations of the hypothalamic-pituitary-adrenal axis activity and sensitivity to glucocorticoids. Clin Endocrinol (Oxf) 55(4):447–454
Ferguson MA, Gutin B, Owens S, Litaker M, Tracy RP, Allison J (1998) Fat distribution and hemostatic measures in obese children. Am J Clin Nutr 67(6):1136–1140
Gower BA, Nagy TR, Goran MI (1999) Visceral fat, insulin sensitivity, and lipids in prepubertal children. Diabetes 48(8):1515–1521
Higgins PB, Gower BA, Hunter GR, Goran MI (2001) Defining health-related obesity in prepubertal children. Obes Res 9(4):233–240
Jessop DS, Dallman MF, Fleming D, Lightman SL (2001) Resistance to glucocorticoid feedback in obesity. J Clin Endocrinol Metab 86(9):4109–4114
Manenschijn L, van den Akker EL, Lamberts SW, van Rossum EF (2009) Clinical features associated with glucocorticoid receptor polymorphisms. An overview. Ann N Y Acad Sci 1179:179–198
Marshall WA, Tanner JM (1969) Variations in pattern of pubertal changes in girls. Arch Dis Child 44(235):291–303
Marshall WA, Tanner JM (1970) Variations in the pattern of pubertal changes in boys. Arch Dis Child 45(239):13–23
Moisan MP (2010) Genotype-phenotype associations in understanding the role of corticosteroid-binding globulin in health and disease animal models. Mol Cell Endocrinol 316(1):35–41
Pasquali R, Anconetani B, Chattat R, Biscotti M, Spinucci G, Casimirri F, Morselli-Labate AM (1996) Hypothalamic-pituitary-adrenal axis activity and its relationship to the autonomic nervous system in women with visceral and subcutaneous obesity: effects of the corticotropin-releasing factor/arginine-vasopressin test and of stress. Metabolism 45(3):351–356
Richard E, Fernandez-Real JM, Lopez-Bermejo A, Ricart W, Déchaud H, Pugeat M, Moisan MP (2009) Corticosteroid binding globulin and glucocorticoid receptor genotypes influence body composition in a male population. Int J Genet Mol Biol 1(4):59–63
Rosmond R, Chagnon YC, Holm G, Chagnon M, Perusse L, Lindell K, Carlsson B, Bouchard C, Björntorp P (2000) A glucocorticoid receptor gene marker is associated with abdominal obesity, leptin, and dysregulation of the hypothalamic-pituitary-adrenal axis. Obes Res 8(3):211–218
Rosmond R, Dallman MF, Bjorntorp P (1998) Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities. J Clin Endocrinol Metab 83(6):1853–1859
Seckl JR, Walker BR (2001) Minireview: 11beta-hydroxysteroid dehydrogenase type 1- a tissue-specific amplifier of glucocorticoid action. Endocrinology 142(4):1371–1376
Stevens A, Ray DW, Zeggini E, John S, Richards HL, Griffiths CE, Donn R (2004) Glucocorticoid sensitivity is determined by a specific glucocorticoid receptor haplotype. J Clin Endocrinol Metab 89(2):892–897
Acknowledgments
We thank Ruth Andrew for measuring urine glucocorticoid metabolites. This work was supported by the Centre Hospitalier Universitaire of Bordeaux (CHU de Bordeaux, France) and INRA.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Barat, P., Corcuff, JB., Tauber, M. et al. Associations of glucocorticoid receptor and corticosteroid-binding globulin gene polymorphisms on fat mass and fat mass distribution in prepubertal obese children. J Physiol Biochem 68, 645–650 (2012). https://doi.org/10.1007/s13105-012-0176-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13105-012-0176-9