Ghrelin is a peptide produced principally in the stomach that increases appetite and participates in stimulation of growth hormone (GH) secretion. Obese children have low GH concentrations that increase after fasting. We hypothesized that an increase in ghrelin concentrations with fasting might participate in the subsequent increase in GH secretion. Subjects included 5 lean girls ages 9 to 14 years in stage I to III puberty who had body mass index standard deviation scores (BMI SDS) of -1.8 to -0.5 and delayed adolescence and/or short stature. Nine obese girls ages 6 to 11 with BMI SDS of 4.0 to 10.6 in stage I to III puberty were also studied. The lean girls and 7 of the obese girls were studied in the ad libitum fed state. Seven obese girls, including 5 studied in the fed state, were studied in the final 24 h of a 48 h fast consisting of 25% of calories estimated to be appropriate for ideal body weight. Blood was obtained every 15 min for 24 h beginning at 0800h and assayed for GH. Total ghrelin was determined in 8 samples consisting of an equal aliquot of each 15-min sample in a 3-hour period beginning at 0800h for 24 h. Lean girls had significantly greater ghrelin concentrations than did fed obese girls (0.41 ± 0.03 vs 1.6 ± 0.01 ng/mL, p < .0001), and fasting increased ghrelin concentrations in the obese children significantly (0.18 ± 0.01 ng/mL, p = .007), although the fasting ghrelin concentrations were still much lower than in the lean children (p = .0001). Diurnal variation of ghrelin concentrations, with greater concentrations from 0500 to 1100h, were seen in the lean subjects (p = .019), but this variation was not seen in either the fed or fasted subjects. Ghrelin concentrations in the fed state demonstrated a significant correlation with BMI SDS (r2 = .45, p = .005). We have shown previously that GH concentrations increase in these same obese girls by 1.6-fold between fed and fasting state (J Clin Endocrinol Metab 2002;87:1885), whereas the increase in ghrelin from fed to fasting state was 1.15-fold. In summary, as in adults, ghrelin concentrations are inversely correlated with BMI such that lean girls have significantly more ghrelin than obese girls. Lean girls have diurnal variation in ghrelin concentrations, with higher concentrations at night, but obese children do not. Unlike in adults, fasting in obese children produces an increase in ghrelin concentrations. Although the ghrelin increase with fasting is smaller than the fasting increase in GH and does not exhibit diurnal variation in obese children, these preliminary data support a potential role for ghrelin in the control of GH concentrations in children.
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