Researchers identify genetic cause of inflammation-related tissue damage that causes type 2 diabetes

Inflammation caused by obesity is one of the leading causes of type 2 diabetes. However, it may be possible to limit inflammation in overweight individuals through gene therapies, according to researchers from Case Western Reserve University.

The team reported in the Journal of Clinical Investigation finding a specific genetic factor that causes obesity-related inflammation. They believe that it may be possible to develop medications that target this process and prevent inflammation from ever taking place. This could limit the burden of chronic diseases, which is continuing to grow at a rapid rate.

Macrophages, which are disease-fighting cells in the immune system, play an important role in healing. However, they can also irritate tissue of the body, causing inflammation. This, in turn, damages the tissue, making it resistant to the effects of insulin. Type 2 diabetes is the last step in this process.



However, the researchers observed that the gene KLF4 dictates how strongly macrophages will respond in the body. This gene is turned on or off by environmental factors such as a high-fat diet, the team found. This explains why obesity triggers an inflammatory response.



In testing on laboratory mice, the researchers showed that animals bred to be deficient in KLF4 were more likely to develop symptoms of type 2 diabetes, particularly when they were fed a high-fat diet. They gained 15 percent more weight than genetically normal mice and developed severe glucose tolerance problems.

The team is currently working to see if they can manipulate levels of KLF4 in animals. If they are able to do so, it could open the door to a range of treatments for type 2 diabetes and other inflammation-related disease like cancer and heart disease. This could represent a major advancement in the prevention of these conditions.

"Would you be able to lose weight, would diabetes go away, would inflammation go away? Possibly," said Mukesh K. Jain, MD, the lead researcher of the study. "We have a shot at a novel treatment for obesity and its complications, such as diabetes, heart disease and cancer."
 
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