Localized Inflammation In The Brain Linked To Overeating, Obesity

A new study led by researchers from the University of California-San Francisco and University of Washington Medical Center revealed that a local inflammation in the region of the brain known as mediobasal hypothalamus (MBH) could trigger overeating and weight gain.

The study, published in the journal Cell Metabolism, showed that eating a fat-rich diet could cause the brain-resident immune cells called microglia to expand in number. The increase in microglia then triggers a local inflammation within the MBH. As a result, an individual may tend to eat more food, burn fewer calories and gain more weight.

For the study, the researchers conducted series of an experiment on animal models. For four weeks, a group of mice was fed with a fast food-like diet rich in fat. It has been known that eating fat-rich diet could increase the number of microglia in the MBH, triggering a local inflammation. Compared to the group of mice under a healthier low-fat diet, the mice fed with fat-rich diet consume more food and burn fewer calories, which resulted in a substantial weight gain.

To determine if the increased number of microglia is responsible for overeating and obesity, the researchers gave the mice on a fatty diet an experimental drug called PLX5622. The drug depleted the number of microglia in the MBH of the mice. Interestingly, these mice ate 15 percent less and gained 20 percent less weight than untreated mice on the same diet. In another experiment, the researchers' genetically engineered mice to prevent microglia from activating inflammatory responses. These genetically engineered mice were also put on a high-fat diet. The researchers observed that these mice ate 15 percent less and gained 40 percent less weight.

"From these experiments we can confidently say that the inflammatory activation of microglia is not only necessary for high-fat diets to induce obesity, but also sufficient on its own to drive the hypothalamus to alter its regulation of energy balance, leading to excess weight gain," said Joshua Thaler, MD, PhD, associate professor of medicine at the UW Medicine Diabetes Institute and senior co-author of the study in a press release. 

The experiments suggest that the local inflammation caused by microglia could be responsible for the animals' overeating and weight gain. To confirm this, the researchers gave a certain drug to a mice fed with healthy, low-fat diet. The drug could activate the inflammatory response of microglia, causing the mice to eat 33 percent more food and expend 12 percent less energy. This led to a 400 percent increased in weight gain compared to the untreated mice on the same healthy diet.