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The phosphorylation status of insulin-like growth factor-binding protein-1 in prepubertal obese children
T Kamoda1, H Saitoh, S Nakahara
1Department of Pediatrics, University of Tsukuba, Tsukuba, Japan. tkamoda@md.tsukuba.ac.jp
Insights
Obese children have lower levels of insulin-like growth factor-binding protein 1 (IGFBP-1), both total and nonphosphorylated. Increased free IGF-I in obese children is linked to reduced total IGFBP-1, not altered IGFBP-1 phosphorylation.
Area of Science:
- Pediatric Endocrinology
- Metabolic Disorders
Background:
- Obesity in children is associated with altered growth factor signaling.
- Insulin-like growth factor-binding protein 1 (IGFBP-1) plays a role in regulating IGF-I bioavailability.
- The phosphorylation status of IGFBP-1 may influence its function.
Purpose of the Study:
- To investigate the effect of childhood obesity on total and nonphosphorylated IGFBP-1 levels.
- To examine the relationship between IGFBP-1 phosphorylation status and obesity.
- To explore the associations of insulin, total IGF-I, free IGF-I, and IGFBP-3 with IGFBP-1 status in obese children.
Main Methods:
- A comparative study involving 19 prepubertal obese children and 15 age-matched controls.
- Serum concentrations of total and nonphosphorylated IGFBP-1 were quantified using noncompetitive radioimmunoassays (RIAs).
- Serum levels of insulin, total IGF-I, free IGF-I, and IGFBP-3 were also measured.
Main Results:
- Obese children exhibited significantly lower serum levels of both total IGFBP-1 (48.7 ± 5.6 µg/L) and nonphosphorylated IGFBP-1 (11.1 ± 1.9 µg/L) compared to controls (86.7 ± 9.0 µg/L and 28.8 ± 6.2 µg/L, respectively).
- The ratio of nonphosphorylated to total IGFBP-1 did not significantly differ between obese and control groups.
- Circulating free IGF-I levels were significantly higher in obese children (P<0.05), while insulin, total IGF-I, and IGFBP-3 levels showed no significant differences.
Conclusions:
- Childhood obesity is characterized by reduced concentrations of total and nonphosphorylated IGFBP-1.
- The elevated free IGF-I observed in obese children is associated with lower total IGFBP-1 levels.
- Obesity-related changes in free IGF-I are independent of alterations in IGFBP-1 phosphorylation status.
Objective:
We measured the total and nonphosphorylated insulin-like growth factor-binding protein (IGFBP)-1 concentrations in obese children to determine the effect of obesity on the status of IGFBP-1 phosphorylation. We also measured the serum levels of insulin, total and free IGF-I, and IGFBP-3 to investigate their relationships to the IGFBP-1 phosphorylation status in obese subjects.
Subjects And Methods:
Nineteen prepubertal obese and 15 age-matched control children were included in the study. The serum levels of total and nonphosphorylated IGFBP-1 were determined by noncompetitive RIAs.
Results:
The serum levels of total and nonphosphorylated IGFBP-1 were significantly lower in the obese group (48.7+/-5.6 microgram/l, P<0.001 and 11.1+/-1.9 microgram/l, P<0.01 respectively) than in the controls (86.7+/-9.0 microgram/l and 28.8+/-6.2 microgram/l respectively). However, the ratio of nonphosphorylated IGFBP-1 to total IGFBP-1 did not differ significantly between the obese and control groups. The circulating free IGF-I level was significantly higher in the obese children than in the controls (P<0.05), while the serum levels of insulin, total IGF-I and IGFBP-3 were not significantly different between the two groups. A stepwise regression analysis of the combined group revealed that only the total IGFBP-1 level was an independent predictor of the free IGF-I concentration (P<0.001).
Conclusion:
The present study shows that both total and nonphosphorylated IGFBP-1 concentrations are decreased in obese children and the increased free IGF-I level in obese children is related to the reduced total IGFBP-1 level, but unrelated to the change in the IGFBP-1 phosphorylation status.