Brain-Derived Neurotrophic Factor and Obesity in the WAGR Syndrome

• Published in: The New England journal of medicine Vol. 359; no. 9; pp. 918 - 927
• Main Authors: Han, Joan C, Liu, Qing-Rong, Jones, MaryPat, Levinn, Rebecca L, Menzie, Carolyn M, Jefferson-George, Kyra S, Adler-Wailes, Diane C, Sanford, Ethan L, Lacbawan, Felicitas L, Uhl, George R, Rennert, Owen M, Yanovski, Jack A
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 28.08.2008
• Subjects: Adolescent; Adult; Biological and medical sciences; Body Mass Index; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - blood; Brain-Derived Neurotrophic Factor - genetics; Child; Child, Preschool; Children & youth; Chromosome Mapping; Chromosomes, Human, Pair 11; Consent; Energy Metabolism - genetics; Female; Gene Deletion; General aspects; Genotype; Haplotypes; Homeostasis; Homeostasis - genetics; Humans; Hyperphagia - etiology; Hypotheses; Male; Medical sciences; Metabolic diseases; Microsatellite Repeats; Nucleic Acid Hybridization; Obesity; Obesity - genetics; Oligonucleotide Array Sequence Analysis; Pain Measurement; Studies; Surveys and Questionnaires; WAGR Syndrome - blood; WAGR Syndrome - complications; WAGR Syndrome - genetics; Medicine; Obesity; Brain derived neurotrophic factor; Nutritional status; Nutrition disorder
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa0801119

This study examined genotype and body-mass index in patients with the Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome. The related genes WT1 and PAX6 are on chromosome 11p13, centromeric to brain-derived neurotrophic factor ( BDNF ), an important gene in energy homeostasis. BDNF haploinsufficiency was linked to childhood-onset obesity and reduced levels of serum BDNF, suggesting a role of BDNF in energy homeostasis. Brain-derived neurotrophic factor ( BDNF ) haploinsufficiency was linked to childhood-onset obesity and reduced levels of serum BDNF, suggesting a role of BDNF in energy homeostasis. Studies in animal models suggest that brain-derived neurotrophic factor (BDNF) plays a key role in energy homeostasis. 1 – 6 BDNF is believed to act primarily within the ventromedial hypothalamus to regulate energy intake 1 , 2 downstream of the leptin–proopiomelanocortin signaling pathway. 3 , 5 In mice, genetic BDNF haploinsufficiency leads to obesity. 7 – 10 Mice that are heterozygous for inactivated BDNF have a 50% reduction in hypothalamic expression of BDNF, and they have hyperphagia and obesity, which are reversed by intracerebroventricular infusions of BDNF. 8 – 10 Although studies in animals provide support for a role of BDNF in energy homeostasis, data in humans are relatively limited. . . .