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Low levels of brain chemical may lead to obesity, NIH study of rare disorder shows
August 28, 2008A 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 obesity.
"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 people.
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 of overeating.
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 individuals.
NIH/National Institute of Child Health and Human Development
"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 people.
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 of overeating.
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 individuals.
NIH/National Institute of Child Health and Human Development
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The current health care debate in the United States is complicated. Trade-offs between heath care expenditures, lifestyle choices and life expectancy have been suggested but seldom clearly demonstrated.
New finding suggests prostate biopsy is not always necessary
Researchers at Wake Forest University School of Medicine and the University of Wisconsin-Madison have discovered that some elevated prostate-specific antigen (PSA) levels in men may be caused by a hormone normally occurring in the body, and are not necessarily a predictor of the need for a prostate biopsy.
Developmental delay could stem from nicotinic receptor deletion
The loss of a gene through deletion of genetic material on chromosome 15 is associated with significant abnormalities in learning and behavior, said a consortium of researchers led by Baylor College of Medicine (www.bcm.edu) in a report that appears online today in the journal Nature Genetics.
Indiana U. at APHA: Studies about health education for people with ID, stability balls at work
An Indiana University study involving adults with intellectual disabilities found that the adults increased their personal health knowledge after taking a semi-weekly class for four weeks.
Physical education key to improving health in low-income adolescents
School-based physical education plays a key role in curbing obesity and improving fitness among adolescents from low-income communities, according to a new study led by researchers at the University of California, San Francisco and UC Berkeley.
Energy gap useful tool for successful weight loss maintenance strategy
Americans continue to get heavier. Most weight control methods short of bariatric surgery are generally considered ineffective in preventing obesity or reducing weight.
TV bombards children with commercials for high-fat and high-sugar foods
Childhood obesity in the United States is reaching epidemic proportions. With more than one fourth of advertising on daytime and prime time television devoted to foods and beverages and continuing questions about the role television plays in obesity.
New scientific study indicates that eating quickly is associated with overeating
According to a new study accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM), eating a meal quickly, as compared to slowly, curtails the release of hormones in the gut that induce feelings of being full.
American Dietetic Association Releases Updated Position Paper Promoting and Supporting Breastfeeding
The American Dietetic Association has released an updated position paper on breastfeeding that details health benefits for both infants and mothers and encourages promotion of breastfeeding whenever possible.
Addressing obesity via the 'energy gap'
The November issue of the Journal of the American Dietetic Association features a commentary by James O. Hill, an honorary ADA member, professor of pediatrics and medicine and director of the Center for Human Nutrition at the University of Colorado-Denver.
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