We all need some fat in our diets, but eating excess amounts of unhealthy fat has been linked to heart disease and obesity, which can cause poor health outcomes. Now scientists at Yale University have used a mouse model to show that a high-fat diet can also lead to changes in the hypothalamus, a region of the brain that helps control food intake and metabolism. Reporting in Cell Metabolism, researchers led by Neuroscience and Comparative Medicine Professor Sabrina Diano investigated the hypothalamic inflammation that a high-fat or high-carbohydrate diets can cause.
Their findings confirmed that hypothalamic inflammation can occur within three days of eating a high-fat diet, long before obesity starts in mice. "We were intrigued by the fact that these are very fast changes that occur even before the body weight changes, and we wanted to understand the underlying cellular mechanism," said Diano.
A mouse model that was fed a high-fat diet displayed changes in the microglial cells of the brain. Microglia are critical to the immune response in the central nervous system. They are able to not only release inflammatory molecules that respond to an invader, but they can also tamp that response down once the threat is resolved.
In this work, the scientists found that there was a quick increase in the levels of a protein called uncoupling protein 2 (UCP2) in animals fed a high-fat diet. When the researchers deleted UCP2 from microglia, their activation was reduced, suggesting the protein plays an important role in that activation. The microglia also had significantly smaller mitochondria. UCP2 helps control energy use in the mitochondria, which impacts the control of glucose levels and energy by the hypothalamus.
Mice that were fed a high-fat diet continued to eat more and get more obese. But animals that lacked UCP2 in their microglia ate less on a high-fat diet and stopped gaining weight.
Diets that are high in fat can affect our bodies, but we are starting to learn more about how they affect our brains. "There are specific brain mechanisms that get activated when we expose ourselves to specific [types] of foods. This is a mechanism that may be important from an evolutionary point of view. However, when food rich in fat and carbs is constantly available it is detrimental," noted Diano.
Diano is also studying how microglia relate to Alzheimer’s and other diseases that are linked to changes in microglia; a correlation has been established between these disorders and obesity.