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Acylated and unacylated ghrelin levels in normal weight and obese children: Influence of puberty and relationship with insulin, leptin and adiponectin levels

Background: Ghrelin circulates in blood as acylated (AG) and unacylated (UAG) ghrelin. The physiological role of the two forms is poorly understood, in particular in childhood. Aim of the study was to evaluate the AG and UAG levels in obese and normal weight (NW) children, pre-pubertal and pubertal, and their relationship with insulin, leptin and adiponectin levels. Subjects and methods: A population-based study in which AG, UAG, leptin, adiponectin, glucose, insulin, testosterone or estradiol levels, insulinemic indexes were evaluated in 82 NW and 58 obese (OB) children. Results: Both ghrelin forms in NW were higher (AG, p<0.02; UAG, p<0.0001) than in OB subjects, with similar ratio AG/UAG. While no differences were observed for gender, puberty AG (p<0.01) and UAG (p<0.0001) levels were higher in pre-pubertal than pubertal NW and OB subjects. Adiponectin levels in NW subjects were higher (p<0.001), while leptin and insulin levels were lower (p<0.0001) than in OB subjects. NW children showed homeostasis model assessment (HOMA) and HOMAβ indices lower than OB children (p<0.0001) with a higher a quantitative insulin sensitivity check index (p<0.0001). AG and UAG levels correlated to each other (p<0.0001), each showing a negative correlation to age, height, weight and body mass index. Both forms, but more strongly UAG, correlated with adiponectin, leptin, and insulin. Conclusions: OB children show lower levels of both AG and UAG when compared to NW subjects, with lower levels during puberty. These results demonstrate a peculiar strong relationship between UAG levels and metabolic parameters in the pediatric population, suggesting a role for UAG in metabolic functions.