Sex-related differences in the association of ghrelin levels with obesity in adolescents

Abstract Background: The utility of ghrelin as a biomarker may be different depending on gender. The aim of this study was to assess ghrelin levels in a population-based sample of adolescents, and to evaluate their association with obesity and obesity-related parameters depending on sex. Methods: The studied population included 601 randomly selected 14-to 16-year-old children. Anthropometrical data were measured and body mass index (BMI) and waist to hip ratio calculated. Body composition was assessed using an impedance body composition analyzer. Total serum ghrelin levels were determined using a multiplexed bead immunoassay. Serum leptin and adiponectin levels were determined by ELISA and insulin by RIA. Results: Ghrelin levels were significantly higher in girls than in boys. Serum ghrelin concentrations were significantly lower (p<0.01) in obese than in normal weight (NW) girls, but showed no differences by weight category in boys. Ghrelin showed a significant negative relationship with waist circumference (WC), waist to hip ratio and fat mass (p<0.05) in both genders, and with weight and BMI (p<0.01) in girls, and insulin (p<0.01) and HOMA (p<0.05) in boys. Ghrelin also correlated negatively with leptin levels in girls (p<0.01). Conclusions: Our study describes serum ghrelin levels in adolescents, showing a sexual dimorphism in ghrelin levels in these 14-to 16-year-old children, and a different association of ghrelin levels with obesity by gender that suggests a different appetite and energy expenditure control depending on sex at this age.

[1]  R. Kelishadi,et al.  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 , 2008, Clinical endocrinology.

[2]  E. Benjamin,et al.  Circulating ghrelin, leptin, and soluble leptin receptor concentrations and cardiometabolic risk factors in a community-based sample. , 2008, The Journal of clinical endocrinology and metabolism.

[3]  C. Zou,et al.  Factors associated with fasting plasma ghrelin levels in children and adolescents. , 2008, World journal of gastroenterology.

[4]  Setting Brazil Establishing a standard definition for child overweight and obesity worldwide: international survey. , 2008 .

[5]  Yuxiang Sun,et al.  Central and Peripheral Roles of Ghrelin on Glucose Homeostasis , 2007, Neuroendocrinology.

[6]  Y. Greenman,et al.  Ghrelin secretion is modulated in a nutrient‐ and gender‐specific manner , 2004, Clinical endocrinology.

[7]  M. Nakazato,et al.  Ghrelin is a growth-hormone-releasing acylated peptide from stomach , 1999, Nature.

[8]  J. Bunt,et al.  Cross-sectional and prospective relationships of fasting plasma ghrelin concentrations with anthropometric measures in pima Indian children. , 2003, The Journal of clinical endocrinology and metabolism.

[9]  M. Nakazato,et al.  Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. , 2002, The Journal of clinical endocrinology and metabolism.

[10]  V. Naganathan,et al.  Gender differences in plasma ghrelin and its relations to body composition and bone – an opposite‐sex twin study , 2007, Clinical endocrinology.

[11]  M. de Oya,et al.  Leptin and adiponectin levels in pubertal children: relationship with anthropometric variables and body composition , 2010, Clinical chemistry and laboratory medicine.

[12]  E. Gabazza,et al.  Circulating levels of active ghrelin is associated with abdominal adiposity, hyperinsulinemia and insulin resistance in patients with type 2 diabetes mellitus. , 2004, European journal of endocrinology.

[13]  D. Yeste Fernández,et al.  [Spanish cross-sectional growth study 2008. Part I: weight and height values in newborns of 26-42 weeks of gestational age]. , 2008, Anales de pediatria.

[14]  C. Richart,et al.  Distribution and determinants of adiponectin, resistin and ghrelin in a randomly selected healthy population , 2005, Clinical endocrinology.

[15]  E. Poggiogalle,et al.  Acylated and nonacylated ghrelin levels and their associations with insulin resistance in obese and normal weight children with metabolic syndrome. , 2009, European journal of endocrinology.

[16]  A. Luke,et al.  Impact of adiponectin and ghrelin on incident glucose intolerance and on weight change , 2009, Clinical endocrinology.

[17]  E. Ghigo,et al.  Oral glucose load inhibits circulating ghrelin levels to the same extent in normal and obese children , 2006, Clinical endocrinology.

[18]  A. Lezcano,et al.  Estudio transversal español de crecimiento 2008. Parte II: valores de talla, peso e índice de masa corporal desde el nacimiento a la talla adulta , 2008 .

[19]  J. López-Siguero,et al.  [Spanish cross-sectional growth study 2008. Part II. Height, weight and body mass index values from birth to adulthood]. , 2008, Anales de pediatria.

[20]  H. Kauma,et al.  Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes. , 2003, Diabetes.

[21]  M. Drent,et al.  The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review , 2007, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[22]  B. Fagerberg,et al.  Plasma ghrelin, body fat, insulin resistance, and smoking in clinically healthy men: the atherosclerosis and insulin resistance study. , 2003, Metabolism: clinical and experimental.

[23]  A. Whatmore,et al.  Ghrelin concentrations in healthy children and adolescents , 2003, Clinical endocrinology.

[24]  J. Purnell,et al.  Ghrelin levels correlate with insulin levels, insulin resistance, and high-density lipoprotein cholesterol, but not with gender, menopausal status, or cortisol levels in humans. , 2003, The Journal of clinical endocrinology and metabolism.

[25]  N. Zhang,et al.  Meta-Analysis of the Relationship Between Obestatin and Ghrelin Levels and the Ghrelin/Obestatin Ratio With Respect to Obesity , 2011, The American journal of the medical sciences.

[26]  T. Reinehr,et al.  Obestatin and ghrelin levels in obese children and adolescents before and after reduction of overweight , 2007, Clinical endocrinology.

[27]  E. Ravussin,et al.  Circulating ghrelin levels are decreased in human obesity. , 2001, Diabetes.

[28]  D. Farmakiotis,et al.  Ghrelin and leptin levels in obese adolescents. Relationship with body fat and insulin resistance. , 2007, Hormones.

[29]  K. Nanjo,et al.  Ghrelin inhibits insulin secretion through the AMPK–UCP2 pathway in β cells , 2010, FEBS letters.

[30]  A. J. van der Lely,et al.  Should we consider des-acyl ghrelin as a separate hormone and if so, what does it do? , 2014, Frontiers of hormone research.

[31]  W. Gulliver,et al.  Serum Acylated Ghrelin Is Negatively Correlated with the Insulin Resistance In the CODING study , 2012, PloS one.

[32]  J. Argente,et al.  Ghrelin levels from fetal life through early adulthood: relationship with endocrine and metabolic and anthropometric measures. , 2004, The Journal of pediatrics.