Researchers have discovered a neural circuit that sends critical signals to tell an animal when it is full and should stop eating. The discovery has relevance for the search for effective ways to treat eating disorders and obesity.

The neural circuits that control hunger are in part controlled by acetylcholine, a message-carrying chemical, or neurotransmitter, produced by a small group of cells in the brain, the new research reveals.  Scientists reported in the October 3 issue of the journal Nature that the release of acetylcholine in the brain suppresses appetite in mice, and that mice whose brains cannot produce acetylcholine eat excessively and gain weight.

The researchers say the receptors that brain cells use to recognize and respond to acetylcholine can also be activated by nicotine, suggesting that this brain circuit may also be involved in conveying nicotine’s appetite-suppressing effects. The finding also suggests that it may be possible to treat eating disorders and reduce obesity with drugs that manipulate acetylcholine signaling in the brain.

Many of the neurons that control hunger are clustered in a brain structure called the hypothalamus. Cells in the hypothalamus integrate signals about the body’s internal needs with sensory information to control a variety of bodily functions, including hunger, thirst, and body temperature. To maintain the body’s energy needs, neurons in the hypothalamus direct an animal to eat when energy stores are running low, and curb hunger when sufficient calories have been consumed.  

The research team was led by Benjamin R. Arenkiel, Ph.D., a NARSAD 2009 Young Investigator and 2014 Independent Investigator at Baylor College of Medicine. They explored beyond the hypothalamus and discovered that acetylcholine-producing neurons in the center of the brain also participate in hunger circuits. Their studies suggest that release of acetylcholine from these cells signals to cells in the hypothalamus and slows eating. When the researchers used genetic manipulation to eliminate acetylcholine-releasing cells from the brains of mice, the animals ate excessively and became obese. Artificially stimulating acetylcholine signaling, in contrast, caused mice to eat less usual.