Researchers have known for some time that diets high in fat tend to be a major causative factor for obesity and the alarming increase in the prevalence of type 2 diabetes. They have also long suspected, and have in recent years found evidence to support those suspicions, that one of the triggers that cause both type 2 diabetes and obesity is inflammation and its weakening effect on the body’s immune system. But what causes the inflammation?
A new study conducted by scientists from The Methodist Hospital and the Methodist Diabetes & Metabolism Institute, and published in the journal Cell Metabolism, may help to answer that question. Our own fat cells cause the inflammation, in response to high-calorie, high-fat diets.
What you eat turns around and eats you
The human body’s ability to overreact to certain foods and substances has long been known. For example, most people have no problem eating peanuts, but for a small percentage of the population exposure even to the smell of peanuts or peanut oil can cause a life-threatening allergic reaction. Similarly, most of us can get stung by a bee and experience little more than a local swelling around the bite and some itching and discomfort, but others can be plunged into anaphylactic shock and within seconds experience difficulty breathing and even death.
The findings of the Cell Metabolism study seem to indicate that a similar phenomenon may happen in the fat cells of our own bodies. Exposed to a high-calorie, high-fat diet, they begin to produce a group of proteins called major histocompatibility complex II, or MHCII. These proteins are part of an immune response, designed to trigger the body’s immune system and help it to fight off bacteria and viruses. When the MHCII response is triggered in obese mice, their fat cells start producing false distress signals, as if they were under attack by pathogens. This causes the fat cells to go slightly crazy and overreact, which causes inflammation.
This was news to the researchers. Although inflammation in fat cells has long been known, and associated with both the development of obesity and type 2 diabetes, it has been assumed that something else triggered the inflammation. Co-author of the study, Willa Hsueh says, “We did not know fat cells could instigate the inflammatory response. That’s because for a very long time we thought these cells did little else besides store and release energy. But what we have learned is that adipocytes [fat cells] don’t just rely on local resident immune cells for protection – they play a very active role in their own defense. And that’s not always a good thing.”
Identifying the source of fat cell inflammation could help to treat obesity
The “good news” about this discovery is that it may be a clue that someday leads researchers to finding a way to treat obesity. By pinpointing MHCII as a cause of inflammation, scientists may also have found a new target for the development of drugs that could block the MHCII response, and thus allow doctors to alleviate some of the dire health consequences of obesity.
One question that the researchers had to deal with in their findings was whether this inflammation reaction on the part of the body’s own fat cells could have a useful purpose. Study co-author Christopher Lyon says, “The expression of MHCII in adipocytes does not seem to be helpful to the body. It is not at all clear what the advantage would be, given all the negative long-term consequences of fat tissue inflammation in people who are obese, including insulin resistance and, eventually, full diabetes. This just appears to be a runaway immune response to a modern high calorie diet.” Hsueh adds, “The bottom line is, you’re feeding and feeding these fat cells and they’re turning around and biting you back. They’re doing the thing they’re supposed to do – storing energy – but reacting negatively to too much of it.”
These study results are preliminary, and the researchers were able to demonstrate this MHCII response in the fat cells of male mice and in fat cells obtained via biopsy from female humans. Much follow-up research must be done to determine whether the same inflammation occurs in female mice and in male humans, and more importantly, to find ways to block it. The next step is to discover the actual antigens involved in the fat cells’ inflammatory response to high-fat diets and weight gain. If that can be done, perhaps we can develop treatments that can teach these fat cells not to overreact, and thus not to produce a reaction that causes even more weight gain.