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Serum Brain-Derived Neurotrophic Factor Concentrations in Lean and Overweight Children and Adolescents

Unit on Growth and Obesity, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-1103

Address all correspondence and requests for reprints to: Jack A. Yanovski, M.D., Ph.D., Unit on Growth and Obesity, National Institutes of Health, 10 Center Drive, Hatfield Clinical Research Center, Room 1-3330, MSC 1103, Bethesda, Maryland 20892-1103. E-mail: jy15i{at}nih.gov.

Context: Brain-derived neurotrophic factor (BDNF) and its receptor appear to be important components of the leptin-signaling cascade involved in energy homeostasis, and mice with BDNF or TrkB gene haploinsufficiency have excessive adiposity. Little is known about the relationship between adiposity and BDNF, particularly in children.

Objective: The objective of the study was to study the association of serum BDNF with measures of adiposity in children.

Design/Setting/Patients: BDNF was determined by a sandwich-type ELISA after an overnight fast in convenience sample of 328 subjects, aged 3–19 yr enriched for extreme obesity. In 43, BDNF was also measured before, and again 1 h after, consuming a high-energy content (787 kcal) milkshake.

Main Outcome Measures: Measures included associations between BDNF and measures of adiposity.

Results: There were no significant univariate associations between log BDNF and adiposity measured by body mass index (BMI), BMI-Z score, or fat mass. However, in an analysis of covariance accounting for age, sex, race, pubertal status, and platelet count, BDNF was lower in overweight children (mean ± SD, 39.8 ± 24.8 vs. 47.0 ± 25.4 ng/dl, P = 0.03); in multiple regression analyses with log BDNF as the dependent variable, BMI (P = 0.03), BMI-Z (P = 0.01), and body fat (P < 0.02) were all negatively associated with BDNF once age, pubertal status, and platelet count were included in the model. Ingestion of a meal did not significantly alter serum BDNF 1 h later (P = 0.26).

Conclusions: Serum BDNF is lower in extremely overweight children and adolescents than those of normal weight. It remains to be determined whether obese individuals with low serum BDNF for age and platelet count have mutations that alter BDNF function.

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