Eating shuts down nerve cells that counter obesity

Mouse study offers hints of orexin’s role in weight gain and narcolepsy

orexin in nerve cells

DIET AID  Nerve cells that produce a molecule called orexin (also known as hypocretin, pink) may counter obesity, a study of mice suggests. 

C.J. Guerin, PhD, MRC Toxicology Unit/Science Source

Fractions of a second after food hits the mouth, a specialized group of energizing nerve cells in mice shuts down. After the eating stops, the nerve cells spring back into action, scientists report August 18 in Current Biology.  This quick response to eating offers researchers new clues about how the brain drives appetite and may also provide insight into narcolepsy.

These nerve cells have intrigued scientists for years. They produce a molecule called orexin (also known as hypocretin), thought to have a role in appetite. But their bigger claim to fame came when scientists found that these cells were largely missing from the brains of people with narcolepsy.

People with narcolepsy are more likely to be overweight than other people, and this new study may help explain why, says neuroscientist Jerome Siegel of UCLA. These cells may have more subtle roles in regulating food intake in people without narcolepsy, he adds.

Results from earlier studies hinted that orexin-producing nerve cells are appetite stimulators. But the new results suggest the opposite. These cells actually work to keep extra weight off. “Orexin cells are a natural obesity defense mechanism,” says study coauthor Denis Burdakov of the Francis Crick Institute in London. “If they are lost, animals and humans gain weight.”

Mice were allowed to eat normally while researchers eavesdropped on the behavior of their orexin nerve cells.  Within milliseconds of eating, orexin nerve cells shut down and stopped sending signals. This cellular quieting was consistent across foods. Peanut butter, mouse chow, a strawberry milkshake and a calorie-free drink all prompted the same response. “Foods with different flavors and textures had a similar effect, implying that it is to do with the act of eating or drinking, rather than with what is being eaten,” Burdakov says. When the eating ended, the cells once again resumed their activity.

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When Burdakov and colleagues used a genetic technique to kill orexin nerve cells, mice ate more food than normal, behavior that led to weight gain, the team found. But a reduced-calorie diet slimmed these mice down.

The results suggest that giving orexin to people who lack it may reduce obesity. But that might not be a good idea. An overactive orexin system has been tied to stress and anxiety, Burdakov says. Orexin’s link to stress raises a different possibility —that anxiety can be reduced by curbing orexin nerve cell activity. “And our study suggests that the act of eating can do just that,” Burdakov says. “This provides a candidate explanation for why people turn to eating at times of anxiety.” 

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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