Implications of gastrointestinal hormones in the pathogenesis of obesity in prepubertal children.

Background: There is a worsening high prevalence of global obesity. Special attention has been paid to the gut-endocrine system, represented by the regulators of appetite. In particular, it has been suggested that ghrelin ("hunger" peptide), and obestatin and glucagon-like peptide-1 (GLP-1) ("satiety" peptides) could play important roles in the pathogenesis of obesity. Objectives: The aims of this study were to compare fasting plasma ghrelin, obestatin, and GLP-1 levels between obese and nonobese prepubertal children, and to assess their relations with fatness indexes and insulin resistance (IR). Subjects and methods: Fifty-two prepubertal obese children and 22 controls were enrolled. Fasting levels of gastrointestinal hormones (ghrelin, obestatin, and GLP-1), glucose, and insulin were evaluated. IR was assessed using the homeostasis model assessment of IR (HOMA-IR) index. Analysis was performed by Mann-Whitney U-test, Kruskal-Wallis test, and Spearman's correlation. Results: Obese prepubertal children and normal-weight controls had similar age distribution. Obese children were more insulin resistant when compared to controls (HOMA-IR: p<0.01). GLP-1 levels were significantly lower in obese children than in controls (p<0.01). Obestatin was significantly higher in obese than normal-weight children (p<0.01), while ghrelin was not different. There was a negative correlation between GLP-1 and standard deviation score-body mass index (r=-0.36, p=0.009) and between GLP-1 and waist circumference (r=-0.45, p=0.001), while no association was observed with HOMA-IR. Conclusions: GLP-1 levels have been shown to be correlated with adiposity indexes, but not with HOMA-IR, suggesting that this hormone could play an important role in the early development of obesity.