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Brain Immune Cells Control Food Intake and Obesity

Researchers have discovered that a type of brain immune cell, called microglia, controls food intake and obesity in mice, providing a novel therapeutic target to combat obesity and its associated health consequences. The research focused on the hypothalamus, a part of the brain governing hunger and other physiologic functions, and was conducted primarily in male mice. Scientists built on previous research showing the association between obesity and the accumulation of microglia in the hypothalamus of people and mice. It was not known, however, whether microglia-induced inflammation played a role in regulating food intake or rather was a consequence of excess food intake. To examine this question, researchers used a drug called PLX5622 to deplete microglia. They found that the drug had no effect on mice eating a standard, low-fat diet. They then compared two groups of mice that were on a high-fat diet. Although both groups gained more weight than mice fed the standard diet, drug-treated mice eating a high-fat diet ate less, gained less weight, and had lower body fat compared to untreated mice also eating a high-fat diet. These and other results suggested that microglia play a role in regulating food intake. To confirm this finding, the researchers performed the opposite experiment: using genetic techniques, they generated mice in which they could activate microglia and induce microglial inflammation. They found that mice with activated microglia were vulnerable to weight gain even on the standard diet, experiencing a rapid, 4-fold increase in the amount of weight gained compared to control mice on the same diet. Contributing to this weight gain, the experimental mice ate more food and had lower energy expenditure (calorie burning) compared to control mice, further suggesting that microglia directly regulate metabolism. Other experiments showed that, when exposed to a high-fat diet, microglia signal to immune cells found in the bone marrow and recruit them to the hypothalamus to participate in the inflammatory response. These results suggest that microglia are key regulators of food intake, calorie burning, and obesity in mice.

If found to play a similar role in women and men, microglia represent novel therapeutic targets for obesity and its associated health consequences. Further research into the detailed mechanisms by which these cells exert their effects—such as understanding how a high-fat diet promotes microglial inflammation in mice—could shed light on other targets and potential therapies.


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