A new study in mice investigating a brain region that controls the animals' impulses to "feed or flee" may have implications for obesity and anxiety in humans, according to its authors.

We know that both too much and too little food can be bad for us. Too little? Stunted growth. Too much? Obesity. The latter can also open the door to diabetes, cardiovascular disease, and cancer.

Studies show that the brain mechanisms that are involved in feeling hungry are highly complex.

For instance, it seems that the nerve signals telling us when it is acceptable to eat are also fired from the same neurons that tell us when to run from danger.

This finding has led scientists to consider whether investigating this mechanism further might provide clues to new treatment targets for obesity or psychiatric conditions that are linked to anxiety.

The researchers behind the new study—from Imperial College London in the United Kingdom—set out to examine this brain mechanism, particularly in regard to a region of the brain called the ventromedial hypothalamus (VMH), which has been a subject of interest in obesity research for a long time.

'Control switch' for feed-or-flee mechanism

In their study—which has now been published in the journal Cell Reports—the researchers used mice with neurons that had been genetically modified to be stimulated by a laser light.

This modification allows scientists to toggle brain regions "off" and "on" by focusing the laser on the required area. When they did this to the VMH, they discovered that a group of cells called SF1 act as a "control switch" for the feed-or-flee mechanism.

SF1 cells are normally very active when mice are anxious—such as when they explore a new environment—but the researchers found that SF1 activity "dampens down" when the mice approach food.

The researchers say that SF1 effectively switches the activity of the VMH from defensive behavior to "need to feed" when the animals discover food. But when the animals' guards were dropped while feeding, the VMH switched back to defensive after eating.

Further investigation showed that the researchers could manipulate SF1 activity in the mice. By making the mice more stressed, they found that they could switch the VMH back to defensive mode, which prevented the mice from being hungry.

When the team administered drugs to the mice to increase activity in their SF1 neurons, the animals were less likely to want food and stored less fat. Dampening down SF1 activity made the mice feel less anxious, but it also made them eat more and put on more weight.

"We have shown for first time," says study co-author Dominic Withers, of Imperial College London's Institute of Clinical Sciences, "that activity in this small population of brain cells acutely changes food intake. That hadn't been shown before."

Eating disorders and stress in humans

Withers and team believe that their findings could be relevant for studies of eating disorders and stress in human subjects.

"There's a long-standing recognition," he says, "that things like obesity are associated with altered anxiety states and altered emotions and depression, so it is a bit of a chicken and egg as to which came first."

Withers believes that small-molecule drugs targeting the SF1 neurons or other relevant "fine control mechanisms" in the brain may have greater potential than some existing treatments.

These are less precise in targeting and therefore have a greater risk of creating unintended adverse effects.

"At the moment we're only in the foothills of discovering how the brain works, particularly the appetite regulatory circuits. But when you start combining these new tools in the lab, we're really moving into a revolution in brain science."

Dominic Withers