A study, reported in Cell Metabolism, found that obese mice with mutated machrophages didn’t develop insulin resistance.
Researchers at the University of California, San Diego School of Medicine say that inflammation provoked by macrophages leads to insulin resistance and type 2 diabetes.
In recent years, it has been theorized that chronic, low-grade tissue inflammation related to obesity contributes to insulin resistance.
The investigators transplanted bone marrow from a global JNK1 knockout mouse into a normal mouse that had been irradiated to kill off its endogenous bone marrow. This resulted in a chimeric mouse in which all tissues were normal except the bone marrow, which is where macrophages originate. JNK1 is a key component of the inflammatory pathway in the macrophage. As a control, the scientists used normal, wild-type mice as well as mice lacking JNK1 in all cell types. These control mice were also subjected to irradiation and bone marrow transfer.
The mice were all fed a high-fat diet. The chimeric mice, lacking JNK1 in bone marrow-derived cells, became obese. They showed, however, an absence of insulin resistance. The chimeric mice also developed fatty livers, which leads to liver inflammation and hepatic insulin resistance but not inflammation.
The findings will be published in the November 7 issue of Cell Metabolism.
