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Putting the brakes on overeating

Restoring a chemical in the gut sends a message to mouse brains to stop overeating

By
2:47pm, September 4, 2013

When people eat high-fat foods, the gut sends a signal to the brain. The brain responds by releasing dopamine, a pleasure chemical. But too much fat causes this connection to backfire. Scientists recently uncovered why and a way to fix the problem in mice. Credit: National Cancer Institute

Eating right can be a big challenge — especially with delicious, high-calorie foods all around. When those calories come from foods high in fat, the gut will reward the diner with a message to the brain that triggers feelings of pleasure. But eating lots of fatty foods can cause this pleasure-signaling pathway to fail. People with this problem tend to respond by eating more to make up for that loss, some research suggests. As a result, they are more likely to become obese. Scientists working with mice now think they’ve figured out why this gut-brain communication breaks down — and how to fix it.

The pleasurable feelings from food are tied to a substance in the brain called dopamine. Too much fat can decrease the dopamine released after eating. In a new study, Ivan de Araujo of Yale University and his coworkers discovered the impaired dopamine signal and what causes it: A fatty diet reduces the body’s production of a chemical called oleoylethanolamine (OH lee ohl eth an OHL ah meen). When the researchers injected this chemical into the guts of mice that had been fed lots of fat, the animals once again received pleasure from eating. And they stopped overeating. De Araujo’s team reported its findings in the August 16 issue of the journal Science.

Although mice and people are vastly different, the new study suggests the strategy to restore the connection is worth investigating for people.

Indeed, the potential for it to help people is “huge,” Paul Kenny told Science News. He's a neuroscientist at the Scripps Research Institute in Juniper, Fla., and did not take part in the new study. Neuroscientists study the function of nerve cells in the brain and other parts of the body.

Food isn't the only thing that can trigger dopamine’s release. Illegal drugs such as cocaine or methamphetamine also can trigger a dopamine “dump” — or release — in the brain.

For the new study, de Araujo’s team performed several experiments on mice. But beforehand, the scientists fed one group of mice a high-fat diet for about three months. Another group of mice got low-fat chow for the same amount of time. All mice were healthy and ate normal diets before the study. But by the end of the three-month period, mice getting high-fat foods were now obese. They had eaten too much.

Now the new experiments began. In one, the scientists confirmed that a high-fat diet sabotaged the brain’s dopamine response. They injected fat directly into the stomachs of the mice. Dopamine levels surged after the injections, but only in mice that had been eating a low-fat diet. The now-obese mice didn't get this pleasure response.

In a second experiment, the researchers measured gut levels of oleoylethanolamine. Previous studies had suggested the chemical helps send a “stop eating” signal to the brain right after a meal and that mice that eat too much fat don’t make enough of it. As expected, more of the chemical showed up in the guts of mice that had been eating a low-fat diet than in the guts of animals that had pigged out for months on high-fat food.

The scientists next wanted to know what would happen if they injected the chemical directly into the guts of a different group of the mice fed a high-fat diet. And their third experiment showed this made a big difference: Dopamine levels in obese mice once again surged after a fat injection in the gut. They ate less and lost weight. The chemical injection seemed to repair the broken gut-brain communication.

The scientists don't know if the same method would help people. But they're planning tests to find out.

Kenny, from the Scripps Research Institute, told Science News that the added chemical appears to offer real potential to help people. Drugs that modify chemicals in the brain often cause severe side effects, like mood changes. But since this chemical is natural and works in the gut — not in the brain — it shouldn’t cause those unwanted changes.

“Maybe it will address obesity and maybe it won't,” Kenny said, “but I think it's a wonderful place to start.”

Power Words

dopamine A neurotransmitter, this chemical helps transmit signals in the brain.

nervous system The network of nerve cells and fibers that transmits signals between parts of the body.

neuroscience Science that deals with the structure or function of the brain and other parts of the nervous system. Researchers who work in this field are called neuroscientists.

neurotransmitter A chemical substance that is released at the end of a nerve fiber. It transfers an electrical signal to another nerve, to a muscle cell or to some other structure.

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