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MEDICAL RESEARCH :
MEDICAL: CONDITIONS: OBESITY :
MEDICAL: GENETICS:
NIH Researchers Link Single Gene Variation to Obesity
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NIH Researchers Link Single Gene Variation to Obesity
Variation in the BDNF gene may affect brains regulation of appetite,
study suggests.
U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH
NIH News
Eunice Kennedy Shriver
National Institute of Child Health and Human Development
http://www.nichd.nih.gov/
Embargoed for Release:
Thursday, October 29, 2015, 12:00 p.m. EDT
http://www.nih.gov/news-events/news-releases/
nih-researchers-link-single-gene-variation-obesity
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A single variation in the gene for brain-derived neurotropic factor (BDNF)
may influence obesity in children and adults, according to a new study
funded by the National Institutes of Health. The study suggests that a
less common version of the BDNF gene may predispose people to obesity by
producing lower levels of BDNF protein, a regulator of appetite, in the
brain. The authors propose that boosting BDNF protein levels may offer a
therapeutic strategy for people with the genetic variation, which tends to
occur more frequently in African Americans and Hispanics, than in
non-Hispanic Caucasians. The study is published in the journal Cell
Reports.
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Obesity in children and adults is a serious issue in the United States,
contributing to health conditions such as heart disease, stroke and type 2
diabetes. Importantly, genetic factors can predispose a person to obesity,
as well as influence the effectiveness of weight-loss strategies. The body
relies on cells to process and store energy, and changes in genes that
regulate these functions can cause an imbalance that leads to excessive
energy storage and weight gain.
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The BDNF gene has previously been linked to obesity, and scientists have
been working for several years to understand how changes in this
particular gene may predispose people to obesity, said Jack A. Yanovski,
M.D., Ph.D., one of the study authors and an investigator at NIHs Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD). This study explains how a single genetic change in BDNF
influences obesity and may affect BDNF protein levels. Finding people with
specific causes of obesity may allow us to evaluate effective,
more-personalized treatments.
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The BDNF protein plays several roles in the brain and nervous system and,
at high levels, the protein can stimulate the feeling of fullness. The
study team, led by Joan C. Han, M.D., a former NICHD investigator now at
the University of Tennessee Health Science Center, first analyzed the BDNF
gene for naturally occurring genetic changes that alter levels of BDNF
production. After analyzing brain tissue samples, the researchers
identified an area of the gene where a single change reduced BDNF levels
in the hypothalamus, a key area that controls eating and body weight.
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The genetic change the researchers identified was not a rare mutation, but
rather a variation that occurs in the general population. Every person has
two copies, or alleles, of each gene, inheriting one copy from each
parent. Alleles can vary at any location across the gene. In their study,
the researchers referred to the common allele as T, and the less common
allele, which produces less BDNF protein, as C.
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Using this information, the researchers studied the BDNF gene in four
groups of people, more than 31,000 males and females, enrolled in clinical
research studies, including PAGE (link is external), HANDLS and Viva La
Familia. They compared a persons BDNF gene combination CC, CT or TT to
factors that define obesity, such as body mass index (BMI) and percentage
of body fat. In African American adults, the team found that the C allele
was associated with higher BMI and body fat percentage in those with CT or
CC types. In a group of healthy children of many races, the researchers
found that CC types had higher BMI scores and percentage of body fat when
compared to CT or TT types, who were similar to each other. Finally, in a
group of Hispanic children, the researchers found that the C allele (CT,
CC types) was associated with a higher BMI score. Overall, the study
suggests that the C allele of the BDNF gene may be linked to obesity in
people.
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To understand why the C allele has an effect on obesity, the study team
carefully examined the genetic area that differs between C and T alleles.
They discovered that the area of interest interacts with a protein called
hnRNP D0B. In laboratory experiments, the team found that hnRNP D0B had
trouble interacting with the C allele, resulting in less BDNF production.
Lower BDNF levels may contribute to obesity in people with the C allele.
If these findings are supported by additional studies, boosting BDNF
levels may prove beneficial, said Dr. Han.
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The study was funded by NICHD and other NIH institutes, including the
National Institute of Mental Health, National Institute of Allergy and
Infectious Diseases, National Institute on Aging, the National Institute
on Minority Health and Health Disparities, the National Institute of
Diabetes and Digestive and Kidney Diseases, and the National Human Genome
Research Institute.
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About the Eunice Kennedy Shriver National Institute of Child Health and
Human Development (NICHD):
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
Institutes website at
http://www.nichd.nih.gov
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About the National Institutes of Health (NIH):
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. NIH is the primary federal agency conducting and supporting
basic, clinical, and translational medical research, and is investigating
the causes, treatments, and cures for both common and rare diseases. For
more information about NIH and its programs,
visit
http://www.nih.gov
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