Inflammation is one of the main reasons why people with diabetes experience heart attacks, strokes, kidney problems, and other, related complications. Now, in a surprise finding, researchers at Washington University School of Medicine in St. Louis have identified a possible trigger of chronic inflammation.
Too much fat in the diet promotes insulin resistance by spurring chronic inflammation. But the researchers discovered, in mice, that when certain immune cells can’t manufacture fat, the mice don’t develop diabetes and inflammation, even when consuming a high-fat diet.
The number of people with diabetes has quadrupled worldwide over the last 20 years, modest progress has been made in making it less likely for some people with diabetes to have heart attacks and strokes. However, those receiving optimal therapy are still much more likely to die from complications driven by chronic inflammation that is, at least in part, generated by these immune cells.
But by blocking the production of fat inside these cells, it may be possible to prevent inflammation in people with diabetes and even in other conditions, such as arthritis and cancer, in which chronic inflammation plays a role. This could have a profound impact on health.
The team made genetically altered mice that could not make the enzyme for fatty acid synthase (FAS) in immune cells called macrophages. Without the enzyme, it was impossible for the mice to synthesize fatty acids, a normal part of cell metabolism. They were surprised to find that the mice were protected from diet-induced diabetes. The mice did not develop the insulin resistance and diabetes that normally would have been induced by a high-fat diet.
Through a series of experiments in the animals and in cell cultures, the researchers found that if macrophages could not synthesize fat from within, the external membranes of those cells could not respond to fat from outside the cells. That prevented the cells from contributing to inflammation. But eliminating inflammation altogether is not the answer to preventing diabetic complications because inflammation is also vital for clearing infectious pathogens from the body and helps wounds heal.
An inhibitor of fatty acid synthase actually is now in clinical trials as a potential cancer treatment, and other drugs have been developed to inhibit fatty acid synthase in diabetes, too. One possibility that the work suggests is that altering the lipid content in the cell membrane may help block cancer metastases and complications of diabetes.
The researchers also plan to take a look at existing drug compounds that change the lipid composition in cells. Such medications failed in clinical trials, but they may have an effect on the membranes of macrophages and therefore may lower the risk of diabetes complications. d.
This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases; the National Heart, Lung, and Blood Institute; and the National Center for Research Resources of the National Institutes of Health (NIH)h.
SOURCE Washington University in St. Louis