August 29, 2008
Low BDNF Causes Appetite And Obesity

A study on humans with a genetic disorder confirms animal studies: low brain derived neurotrophic factor (BDNF) causes unusually strong appetites and obesity.

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 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."

Not all adults with WAGR syndome have the BDNF deletion. Those with WAGR without the deletion do not have a higher rate of obesity.

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.

Leptin, a known appetite regulator, might work by controlling release of BDNF by the hypothalamus. Perhaps BDNF injections could suppress appetite in obese people.

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.

If the BDNF release by the hypothalamus then reaches the rest of the brain by the bloodstream that opens up the possibility of injecting BDNF into the bloodstream as a treatment to reduce appetite. Injection has obvious downsides such as that you have to do it in the first place. Diabetics already carry this burden. Poking a needle into yourself one or more times a day is a painful and potentially dangerous chore and need to store the BDNF in a refrigerator are all downsides. Plus, the injection regime would tend to cause larger and less frequent bursts of blood BDNF than natural hypothalamus release. What we need: embeddable reservoirs that would gradually release the BDNF. Another possibility: Use gene therapy to convert some cells in the body into BDNF producers.

As the cost of genetic testing and other biological testing comes down the rate of discoveries such as this one will only go faster and faster until most of the biological mechanisms in the human body are understood. With these discoveries will come a big shrinkage of our perceived ability to act with free will. So many genes will be found to have variants that influence behavior that a growing portion of all that we do will be attributed at least partially to genetic causes.

Share |      Randall Parker, 2008 August 29 06:55 AM  Brain Appetite

James Bowery said at August 29, 2008 2:34 PM:

So, sedentary lifestyle contributes to obesity directly through low calorie consumption, but it also does so indirectly by lowering BDNF.

And, of course, cognitive decline is related not only to lowered BDNF, but to brain circulatory problems caused by obesity.

It might be good for some brain power to be put into the problem of increasing the habitual level of exercise before the brain power disappears due to a lack of exercise.

Annie Swann said at March 15, 2009 1:18 PM:

My niece was one of the participants in this study. Although she is missing BDNF, obesity and the pattern of overeating did not start until AFTER early onset menopause. However, the lack of exercise in many cases is due to the other illnesses associated with this rare disease, low muscle tone, Achilles tendon issues, poor renal function to name a few. Suggest you study further the diagnoses involved in these young people before you decide they choose not to exercise.

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