Brain Chemical May Play Part in Obesity Puzzle

With an estimated 67 million obese and an additional 75 million overweight adults, it is clear America has an obesity health crisis on its hands. Experts predict that, if the current trend continues, two in every five adults and one in every four children in the U.S. will be obese by 2015. So what can we do about this growing epidemic? It's not just a matter of reminding people of the importance of a proper diet and exercise. Research has found that certain characteristics, such as genetic and physiological factors, impact an individual's risk for gaining and maintaining weight, and therefore may affect overweight and obesity issues. Studies of mice have determined that animals missing a working copy of the BDNF gene were prone to excessive eating and obesity, but the importance hadn't been proven in human beings-until now.

In an effort to understand the role genetic factors play in obesity, researchers at the National Institutes of Health looked at a group of 33 people who had a rare genetic condition called WAGR (pronounced wagger) syndrome, which is an acronym for its symptoms: Wilms' tumor (of the kidneys), aniridia (absence of the iris), genital and urinary tract abnormalities, and mental retardation. Some people with WAGR lack a gene for the brain chemical BDNF—brain-derived neurotrophic factor—which animal studies have suggested may help control appetite and weight. Low levels of the chemical have also been linked to long-term memory loss and difficulty sensing pain.

Of the 33 study participants, 19 (58 percent) had deletions of all or a major portion of one copy of the gene for BDNF and had correspondingly low blood levels the chemical. All 19 of these participants were obese by age 10 and had a strong tendency to overeat. On the other hand, the participants with two working copies of the BDNF gene were no more likely to develop obesity in childhood than the general population and did not report high levels of overeating. "This is a promising new lead in the search for biological pathways that contribute to obesity," Dr. Duane Alexander, director of the U.S. National Institute of Health's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), said in an institute 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."

The senior author of the study, Jack A.Yanovski, M.D., Ph.D., of NICHD's Unit on Growth and Obesity, explained that BDNF is believed to work in combination with other substances that regulate appetite and body weight, primarily leptin, a hormone secreted by fat cells that triggers the release of BDNF in the hypothalamus. Leptin was discovered in 1994 and was found to not only control food intake, but also to impact other functions that are affected by energy balance which could relate to obesity. Research has shown that overweight individuals have high concentrations of leptin in the blood, indicating that they do not respond to leptin by reducing food intake. "We're looking at a small part of what is really a large and complex puzzle," Dr. Yanovski told Reuters Health in a telephone interview. "We guess there are probably about 300 genes that affect body weight in some form or another."

In an accompanying article, Philippe Froguel, M.D., Ph.D., and Alexandra Blakemore, Ph.D., of Imperial College London, wrote that even in this early stage of obesity genetics, the implications for risk projection and patient care are heartening. Although unwise lifestyle choices fuel the current obesity epidemic, they said, some individuals carry "environmental sensitivity" genetic variants that make them particularly susceptible to weight gain when exposed to the current Western lifestyle. They concluded that additional obesity genes expressed in the central nervous system should be revealed soon, opening new avenues for prevention and clinical care.

The findings are published in the August 28 issue of the New England Journal of Medicine.