Fat Cells Under Attack: How a high calorie diet leads to diabetes and disease
Researchers from the Methodist Hospital System have discovered how fat cells thwart the immune system to lead to diabetes and other chronic diseases. Eating a high calorie diet makes adipocytes (fat cells) behave like they’re under attack from pathogens like viruses or bacteria, causing widespread inflammation that triggers an immune system response and disease.
The researchers found high calorie diets can make fat cells believe they are infected. The scientists say until now they thought fat cells were used to store and release energy. It turns out high calorie diets causes a release of proteins known as major histocompatibility complex II (MHCII) that are normally released to fend off infection.
But the researchers aren’t sure what purpose that serves.
A major component of MHCII is the T-cell that mediates our immune response. Investigators for the current study say in obese mice and humans, fat cells are sending out ‘false distress signals’ that agitates the immune system to promote inflammation. Lead study investigator and Methodist Diabetes & Metabolism Institute Director Willa Hsueh, M.D. said in a press release said researchers didn’t know fat cells could do that.
"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”, Hsueh said in a press release.
“This just appears to be a runaway immune response to a modern high calorie diet” The researchers adds, Feeding fat cells with more calories leads to a vicious cycle, but when we eat more calories fat cells are “…turning around and biting you back.”
The finding, published in the journal Cell Metabolism, gives new insights into why obesity leads to diabetes, cancer and other chronic illnesses because it thwarts the immune system.
For the study, researchers looked at cells from overfed obese mice and biopsied fat cells from obese humans, finding a complexity of events that take place, starting with excess nutrients.
The researchers say when we eat what we don’t use for energy it triggers release of leptin – the so-called hunger hormone. Leptin then triggers specialized CD4-T cells to produce interferon gamma. The T-cells then release MHC II that causes fat cells to become inflamed.
Hsueh and her colleagues found that overfed mice lacking MHCII had less inflammation.
Interferon gamma that releases CD4-T cells makes inflammation even worse by causing M2 macrophages to turn into a different kind of pro-inflammatory cell known as M1. Macrophages are a type of white blood cell that fights infection.
RNA microanalysis of fat biopsied tissues allowed the researchers to see which genes were increased in overweight people. They found high expression of most MHCII complex and MHCII antigen processing genes that correlated in what they found in mice after two weeks of being fed a high fat diet.
Lead author Tuo Deng, Ph.D. said until now “…no one knew the signals that start inflammation.
Now that the researchers know what triggers inflammation that can lead to diabetes and other diseases, they hope to find a way to block the process.
Image credit: Bing