Yale scientists may have figured out the reason you keep gaining weight

A particularly intense bout of stress often triggers or exacerbates additional symptoms. It varies from person to person; some may get a stomach ache when they’re stressed, others become depressed or anxious after a stressful encounter, and many say stress worsens pre-existing conditions like diabetes, arthritis, asthma, and other inflammatory diseases.

Puzzlingly, when we’re feeling stressed our bodies release two main hormones (cortisol & adrenaline) that work to decrease inflammation. Therein lies the paradox. If our bodies release anti-inflammatory hormones when stressed, why does stress cause so many side effects and seemingly worsen inflammation in the body?

Scientists have long been mystified by this question, but a new study from Yale University finally has an answer. Researchers performed a “fat check” on brown fat cells, and discovered when someone is feeling stressed out their brown fat releases an immune system activating protein that significantly ramps up inflammation.

So, when we’re stressed, our brown fat becomes stressed out as well, activating the immune system and increasing inflammation throughout the body.

“In the clinic, we have all seen super-stressful events that make the inflammatory disease worse, and that never made sense to us,” says corresponding study author Dr. Andrew Wang, assistant professor of internal medicine and immunobiology, in a university release.

Brown fat, for reference, is quite different from traditional white fat. Brown fat heats the body in cold environments and isn’t associated with obesity or excess weight at all. In fact, brown fat is typically considered “good fat.”

More specifically, the study’s authors discovered that brown fat cells release the protein interleukin-6 (IL-6) in response to stress. Not only does this protein trigger bodily inflammation, but it’s also been linked in the past to a host of other ailments like cancer, obesity, anxiety, depression, diabetes, and various other autoimmune diseases.

Suffice to say, there’s ample evidence that this protein is indeed the culprit researchers have long sought.

What was the genesis of this discovery? Researchers first took note of IL-6 after drawing blood from a group of lab mice. As you can probably imagine, having blood drawn is a pretty stressful experience for a mouse. So, when their blood samples showed elevated levels of IL-6, researchers had a hunch they were on to something.

Now, IL-6 has long been known to be released by the body in the event of infections; the protein activates the immune system in response to a threat. Subsequent experiments with those lab mice, however, revealed that the protein is also released in response to stress, worsening bodily inflammation in the stressed-out rodents.

When the team at Yale pinpointed exactly where the IL-6 was being secreted from in the mice, they noted it was originating from brown fat cells. This was confirmed when signals from the rodents’ brains to brown fat cells were blocked. When that happened, stressful events no longer caused increased inflammation among the mice.

“This was a completely unexpected finding,” says Hua Qing, a postdoctoral associate at Yale School of Medicine.

All of these findings provide some big answers, but also raise more questions. Why is IL-6 released in response to stress in the first place? Surely not just to ramp up inflammation, as that makes no sense. With this in mind, the study’s authors theorized that IL-6 must play some kind of role in the body’s “fight or flight” response.

Sure enough, they found that IL-6 also helps the body produce more glucose in anticipation of a threat. Moreover, brown fat cells appear to release IL-6 well after the body has already produced more cortisol and adrenaline. This pattern, according to the research team, offers up a possible explanation as to how stress can increase inflammation despite the release of immune-suppressing hormones.

Next, the rodents’ ability to produce IL-6 was blocked. When this was done, the mice didn’t experience nearly as much inflammation when stressed and even appeared less on edge during stressful situations.

Regarding the connection between stress and mental health disorders like depression and anxiety, the study’s authors also believe IL-6 is involved. Many people suffering from depression report a lack of appetite and sex drive. Those same symptoms are synonymous with various infectious diseases like the flu. But, when a person is sick with the flu and has no appetite, that isn’t caused by the flu itself but by the body’s immune reaction, which is triggered by IL-6.

“There is ever-growing literature on the role of IL-6 outside of immunity. Our work is exciting because it contributes to shortening that gap of knowledge,” concludes Reina Desrouleaux, a graduate student in biology and biomedical science in Wang’s lab.

The full study can be found here, published in Cell.