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Brain-derived neurotrophic factor haploinsufficiency linked to obesity
Brain-derived neurotrophic factor may play role in energy homeostasis.
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Among patients with the Wilms’ tumor, aniridia, genitourinary anomalies and mental retardation syndrome, brain-derived neurotrophic factor haploinsufficiency was associated with lower levels of serum brain-derived neurotrophic factor and with childhood-onset obesity, according to study findings.
Researchers from the National Institutes of Health in Bethesda, Md. examined the relationship between genotype and BMI in patients with the Wilms’ tumor, aniridia, genitourinary anomalies and mental retardation syndrome (n=33).
“This is a promising new lead in the search for biological pathways that contribute to obesity,” Duane Alexander, MD, director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, said in a press release. “This finding may eventually lead to the development of new drugs to regulate appetite in people who have not had success with other treatments.”
Missing gene linked to obesity
Deletions of chromosome 11p ranged from 1.0 megabase to 26.5 megabases, and 58% of the patients had heterozygous brain-derived neurotrophic factor (BDNF) deletions, according to the researchers. Throughout childhood, these patients had higher BMI z scores than patients with intact BDNF. When aged 8 to 10 years, the z score in patients with heterozygous BDNF deletions was 2.08 ± 0.45 vs. 0.88 ± 1.28 in patients without deletions (P=.03).
At age 10 years, all patients with heterozygous BDNF deletions were obese compared with 20% of patients without heterozygous BDNF deletions (P<.001), according to the researchers.
The critical region for childhood-obesity onset was located within 80 kilobases of exon 1 of BDNF; serum BDNF concentrations were 50% lower in patients with heterozygous BDNF deletions (P=.001), according to the researchers.
“Hyperleptinemia is a hallmark of almost all forms of obesity; thus, understanding the role of downstream mediators of leptin action such as BDNF holds promise for laying the groundwork for the development of new pharmaceutical approaches to the global obesity epidemic,” the researchers wrote.
“Further studies are needed to assess the potential therapeutic role of BDNF replacement in people in whom insufficient BDNF protein is produced and the potential contributions of more common allelic variants at the locus for susceptibility to obesity among people in the general population.”
N Engl J Med. 2008;359:918-927.