While nearly everyone is guilty of overeating from time to time, some people may be more genetically prone to excessive munching than others.
At least that's what Maribel Rios, assistant professor of neuroscience at the Tufts Sackler School for Biomedical Sciences, has found. She and her team of neuroscientists recently concluded that a certain gene, the brain derived neurotrophic factor (BDNF), is crucial for regulating satiety in mice.
BDNF encodes for a protein located within the brain and the periphery.
During a meal, the gut, stomach, liver and other organs secrete signals that bind to receptors in two regions of the brain: the hypothalamus and the dorsal vagal complex. This binding triggers other molecular and cellular events, which result in a behavioral output, like the desire to stop eating.
According to Rios' research, BDNF in the brain plays an important role in the processing of these signals arising from the periphery.
The protein is not only present during human development, but also during adulthood, according to Rios.
"Because it's highly conserved among species, including mammals, the implication is that it's pretty important," Rios said.
While BDNF facilitates many of the neuronal functions, Rios and her team decided to concentrate on one relationship above all others.
"In my lab, we try to focus on its relationship with appetite control and effective behavior," Rios said. "We already knew that if you get rid of BDNF during development you get an animal that is really obese. The reason that these animals are so obese is that they can't stop eating. We found that whereas female mutant mice were 200 percent heavier, mutant males had a 100 percent increase in body weight," Rios said.
Rios noted that this increase was quite striking.
"To me, the implication is that [BDNF] is a pivotal factor in appetite suppression - nature can't really compensate for this lack," she explained, explaining that other labs had come to similar conclusions.
But after some research, Rios and her Sackler team were faced with the question of whether a lack of BDNF in the brain during adulthood would lead to an over-consumption of food.
"In all of the mice which were obese, the expression of BDNF was terminated during a developmental period. Was this obesity due to a developmental brain abnormality or a lack of BDNF activity in the mature brain? These possibilities are not mutually exclusive," Rios said.
Rios hoped that the latter, a decrease in activity in the mature brain rather than a brain abnormality, would be the result.
"A malformed brain is not very easy to fix, but if BDNF signaled for satiety, if you can restore it, then obese individuals might have more control over how much they eat," she said.
The team tested this hypothesis.
"We were able to show that caloric signals, especially glucose, indeed increase levels of BDNF in the hypothalamus. This is consistent with it playing a part in meal termination," Rios said. "But the real proof was to get rid of the gene in an adult animal when development of the brain had been completed. We exclusively got rid of it in sub-regions of the hypothalamus called the ventromedial and dorsomedial hypothalamus."
These regions are particularly crucial for controlling body weight.
After Rios deleted BDNF through genetic manipulation, she noticed a drastic change.
"These animals showed excessive eating and became obese," she said.
According to Rios, the result occurred quickly, within days of depletion of BDNF at a maximal level.
"This was a really exciting finding. Effectively it makes the BDNF pathway a viable target to develop therapies to treat morbidly obese patients," Rios said.
Because the BDNF gene in mice and the BDNF gene in humans are related, the link between obesity and the gene could help in the development of future treatments for a large number of people.
