Could repurposing a depression drug help burn belly fat?

Reduce Fat
Unraveling the immune system's role in metabolism could lead to new ways of fighting belly fat.

As most people who are trying to lose weight can testify, the older you get, the harder it is to burn that ever-growing roll of belly fat. Even if you increase your daily exercise, belly fat will continue to accumulate as you age. Scientists at Yale believe they’ve found an immune connection to this problem—and a possible solution in an existing class of depression drugs.

A team of scientists at Yale, the University of Tennessee Health Science Center and the University of Bonn zeroed in on macrophages, immune cells that are primarily engaged in fighting infections. They discovered a new type of macrophage in the nerves that are inside belly fat. As these macrophages age, they become inflamed, which hampers the chemical messaging involved in fat metabolism.

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The researchers took fat tissue from young and old mice, isolated the immune cells and then sequenced them. When they lowered an inflammation-associated receptor called NLRP3 in the cells, they discovered that chemical messaging returned to the levels that would normally be found in younger mice, which in turn induced fat burning.

"The key finding is that the immune cells talk to the nervous system to control metabolism," said Vishwa Deep Dixit, Yale professor of comparative medicine and immunobiology, in a press release.

The research team then tried blocking an enzyme called monoamine oxidase-A or MAOA in the older mice. MAOA is known to become more prevalent in macrophages as they age. Inhibiting the enzyme also restored fat metabolism to rates normally seen in younger animals. The research was published in the journal Nature.

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MAOI inhibition (or MAOAi) was the mechanism of action for the first major class of antidepressants, which included drugs like isocarboxazid and phenelzine. These drugs are rarely used now, however, because they can cause side effects like high blood pressure. While it is possible that MAOIs could be repurposed to treat obesity in older people, more research would need to be done to test their safety and prove that they can have a positive impact on belly fat, Dixit said.

In the fight against obesity, researchers have become increasingly focused on the role of the immune system in burning fat. Earlier this year, a group of European researchers described how immune cells called eosinophils are greatly diminished in obesity, endangering the health of blood vessels and raising the risk of high blood pressure. And scientists at Sanford Burnham Prebys Medical Discovery Institute are studying the role of natriuretic peptides in signaling that helps turn harmful white fat into healthy brown fat.

The Yale-led team is planning further experiments to shed light on how immune cells interact with nerves to influence health and disease. They hope to learn whether controlling inflammation in immune cells produces enough of an improvement in metabolism to not just burn belly fat, but also to improve the overall aging process.