A new Yale study may help scientists develop novel treatments for obesity.
Researchers at the Yale School of Medicine have identified a chemical messenger in the gut that links chronically high-fat diets to patterns of brain activity that encourage obesity. The finding not only provides researchers with a new target for modulating how the body processes the mental rewards from food, but also has treatment implications for other substance abuse disorders. The study was published in the journal Science on Aug. 16.
“We discovered that there is this specific molecular messenger in the intestine that seems to be responsible for the alteration in brain reward function that we usually observe in obese individuals,” said Yale senior author and professor of psychiatry Ivan de Araujo.
Past research has established that chronically fatty diets lead both to suppressed levels of dopamine activity in the reward center of the brain and reduced synthesis of an appetite-suppressing lipid messenger called OEA. Reduced dopamine function makes a given experience, like consuming food, less subjectively rewarding, and individuals compensate for the deficiency by seeking more of the reward — such as eating additional food.
To probe the link between the reduced dopamine and OEA activity, de Araujo and his team administered OEA to mice on high-fat diets. These mice given OEA saw restored dopamine responses to food and increased likelihood of eating a less fatty diet.
The study presents researchers with multiple targets for treating obesity, said Scripps Research Institute neuroscience professor Paul Kenny. While he is skeptical that directly administering OEA to humans will be an effective treatment because a very large amount of the lipid would be needed to restore dopamine function, Kenny said future therapies could target some of the known pathways that communicate changes in OEA to the dopamine systems in the brain.
“I think it is fascinating that the gut can have such a large role on the brain,” Kenny said. “From a philosophical perspective, I think that’s very, very interesting — that you can have something like the gut telling the brain how to act and not the other way around.”
The dopamine pathways blunted in obesity are similarly pathological in other impulsivity disorders like drug addictions, said Yale School of Medicine professor of psychiatry Dana Small. Many pharmacological treatments for impulsivity disorders target the brain and have negative side effects, and Small said the study will help researchers develop therapies that modulate the same brain systems indirectly and without the side effects. She added that it is “really exciting” that the detrimental neural adaptation that occurs with high fat feeding seems to be reversible.
While the study’s testing of mice is a “screamingly obvious shortcoming” for its human implications, Kenny said mice and humans share physiologically similar feeding behaviors. De Araujo said he now plans to apply the research from mice to gut-brain interactions in humans.
“I am confident that these findings will have some relevance to the human condition,” Kenny said.
According to the Centers for Disease Control and Prevention, approximately one in three American adults are currently obese.