|Low Levels of Brain Chemical May Lead to
Obesity, NIH Study of Rare Disorder Shows
A brain chemical that plays a role in long term memory also appears
to be involved in regulating how much people eat and their likelihood
of becoming obese, according to a National Institutes of Health
study of a rare genetic condition.
Brain derived neurotrophic factor (BDNF) is, as its name implies,
produced in the brain. Studies of laboratory animals have suggested
it also helps control appetite and weight. The NIH study, appearing
in the August 28 New England Journal of Medicine, provides the
first strong evidence that BDNF is important for body weight in
human beings as well.
The NIH researchers studied children and adults with WAGR syndrome,
a rare genetic condition. The researchers found that some of the
people with this syndrome lack a gene for BDNF and have correspondingly
low blood levels of the substance. The people in this subgroup
also have unusually large appetites and a strong tendency towards
“This is a promising new lead in the search for biological pathways
that contribute to obesity,” said Duane Alexander, M.D., director
of the NIH’s Eunice Kennedy Shriver National Institute of Child
Health and Human Development. “This finding may eventually lead
to the development of new drugs to regulate appetite in people
who have not had success with other treatments.”
The study’s first author was Joan C. Han, M.D. and the senior
author was Jack A. Yanovski, M.D., Ph.D., both of NICHD’s Unit
on Growth and Obesity. Other authors of the study were from the
National Human Genome Research Institute and the National Institute
on Drug Abuse, also part of the NIH. Funding for the study was
provided by the NICHD and the NIH Office of Rare Diseases.
WAGR syndrome is an acronym for the complex of symptoms seen in
people who have the condition. These include Wilms tumor, a tumor
of the kidneys; aniridia, absence of the iris, in the eye; genital
and urinary tract abnormalities; and mental retardation. WAGR syndrome
occurs in one out of every 500,000 to 1 million persons.
People with WAGR syndrome lack genes that are grouped on chromosome
11. All people with WAGR syndrome lack two specific genes, called
WT1 and PAX6, but each person can also be missing other nearby
genes. For the most part, human chromosomes are arranged in pairs,
and the genetic deletions found in WAGR syndrome occur on only
one of the two copies of chromosome 11.
WT1 and PAX6 are located in the region of the chromosome that’s
near the gene for BDNF. For this reason, the NIH researchers examined
chromosome 11 from WAGR syndrome patients to learn if the gene
for BDNF was affected, explained Dr. Yanovski.
Studies of mice had determined that animals missing a working
copy of the BDNF gene were prone to excessive eating and obesity.
Studies in human beings, however, hadn’t proved that BDNF was important
In the current study, the NIH researchers conducted analyses of
chromosome 11 in 33 patients with WAGR syndrome. A total of 19
patients (58 percent) had deletions of all or a major proportion
of one copy of the gene for BDNF. By age 10, all of the 19 were
obese and were reported to have a strong tendency to overeat. Moreover,
all of the 19 had blood levels of BDNF that were roughly 50 percent
lower than those of patients who had two working copies of the
BDNF gene. The patients who had two working copies of the BDNF
gene were no more likely to develop childhood onset obesity than
the general population, and did not report unusually high levels
Dr. Yanovski explained that BDNF is believed to work in combination
with a variety of other substances that regulate appetite and body
weight. Chief among these is leptin, a hormone found to be involved
in signaling hunger. Dr. Yanovski added that release of BDNF in
the hypothalamus, a part of the brain involved in controlling eating,
is believed to be indirectly triggered by leptin. Studies of the
relationship between the two, and of BDNF’s action on tissues,
may lead to the development of new drugs to treat obesity in some
The NICHD sponsors research on development, before and after birth;
maternal, child, and family health; reproductive biology and population
issues; and medical rehabilitation. For more information, visit
the Institute’s Web site at http://www.nichd.nih.gov/.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and Centers
and is a component of the U.S. Department of Health and Human Services.
It is the primary federal agency for conducting and supporting basic,
clinical and translational medical research, and it investigates
the causes, treatments, and cures for both common and rare diseases.
For more information about NIH and its programs, visit www.nih.gov.