Researchers Identify Malfunctioning Satiety Signal in Mice Fed a High-fat Diet and Its Link to Dopamine in the Brain
A group of scientists has identified a chemical produced in the gut that regulates the sense of satiety, or fullness, in mice after dietary fat consumption by inducing dopamine release in the brain, a process that is disrupted after excessive high‑fat feeding. The feeling of satisfaction following ingestion of food is caused by a chemical in the brain called dopamine. A significant amount of dopamine is usually released by the brain after eating, resulting in a sense of gratification or reward. For unknown reasons, however, prolonged eating of a high-fat diet leads to desensitization of this signal, which is believed to contribute to overeating in order to compensate for a dampened feeling of satisfaction. Researchers studying this phenomenon in a mouse model identified a chemical produced by the gut in response to eating that can cause dopamine release in the brain. However, if the mice are fed high‑fat diets for several weeks, the levels of this chemical, called oleoylethanolamine (OEA), are reduced. When the group supplied OEA directly to the intestine, the mice reduced their fat intake and lost weight, supporting OEA’s role in promoting satiety. The scientists, interested in how OEA was signaling to the brain in these mice, found that OEA’s effects require a factor called PPARα. They also found that the signal generated by OEA and PPARα is probably transmitted through the vagus nerve, which carries signals between the intestines and the brain, because infusion of OEA directly into the stomach did not seem to affect mice that lacked functional vagus nerves. The scientists next enabled the mice to self‑administer fat directly to their stomachs, bypassing the mouth and therefore the ability to taste the incoming food. When mice on prolonged high‑fat diets were fed in this manner, they were less likely to keep self‑administering the fat than the mice on low‑fat diets, suggesting that the dopamine‑mediated reward response was impaired in the high‑fat fed mice. But when mice on the high‑fat diet were given OEA, they self‑administered more fat, suggesting that OEA restores the dopamine‑mediated reward signal associated with eating that had weakened in these mice. This study supports a model whereby a long‑term, high‑fat diet suppresses the production of OEA in the gut, resulting in a decrease in the production of dopamine in the brain and a dampening of the reward signals that usually accompany eating foods high in fat. This could mean that the desire to eat high‑fat foods is strongly affected by these chemical signals originating in the gut, which could point to new therapeutic options for suppressing appetite and treating obesity in people.