Brain-Derived Neurotrophic Factor and Obesity in the WAGR Syndrome

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. . . .