Obesity is a serious problem worldwide and is a risk factor for diseases such as type II diabetes, heart disease, and fatty liver disease. The main element in the development of obesity is fatty tissue, which contains fat cells (called adipocytes, specialized in storing fat) and macrophages (cleansing cells of the immune system, usually associated with the destruction of microbes).
Along with researchers from Poland, Germany, Australia and Austria, a team of Viennese scientists at MedUni have now discovered valuable fatty tissue macrophage (ATM) signaling pathways in obesity that prevent lipotoxicity. Lipotoxicity is the process of fat molecules accumulating in non-adipose tissue. This research has been published in the journal above Nature’s Metabolism.
In this study, researchers studied, among others, CeMM (Research Center for Molecular Medicine of the Austrian Academy of Sciences) and some of the University of Graz, specifically the PI3K signaling pathway. This is a major metabolic regulator because it regulates fat storage and plays an important role in the cellular response to the hormone insulin. In obesity, reduced insulin action or insulin resistance can lead to type II diabetes, which is associated with high blood glucose levels.
Gernot Schabbauer of the Vienna Institute of Vascular Biology and Thrombosis Research at the MedUni Vienna Center for Physiology and Pharmacology and lead author of the study has spent several years studying the pathway of PI3K signaling in immune cells: “PI3K has been shown to play a key role in metabolic processes. in macrophages. “Julia Brunner, author of the study, added:” ATMs are like Dr. Jekyll and Dr. Hyde; in obesity, they can be good or bad. An active PI3K signaling pathway might balance “good.”
Using techniques such as multi-color flow cytometry, lipidomics, cellular respiration testing, and some animal models, scientists have found that sustainable activity of the PI3K signaling pathway can improve macrophage balance: especially when specialized ATMs are created. MARCO (receptor for macrophages with a collagen structure) on the surface of predatory receptors.
We found that these ATMs that indicate MARCO are professional lipid cleaners. These cells absorb and break down fats according to MARCO, thus preventing them from entering the bloodstream. “
Andrea Vogel, lead author of the research and PhD student in immunology at MedUni Vienna
Omar Sharif, author of the study, added: “Metabolic syndrome and lipotoxicity are hallmarks of obesity. Our work indicates that increased lipid consumption and improved energy metabolism in ATMs help maintain systemic metabolic health. -Creating the impacts of some metabolic diseases.”
Subsequent research will be conducted to determine whether PI3K signaling may also have a lasting effect on human ATMs. “Although moderate inhibition of PI3K has been discussed as a therapeutic strategy to treat metabolic diseases, our data show unexpected side effects. These may lead to changes in blood lipid levels, resulting in reduced fat absorption at ATMs,” says Schabbauer. .
Vienna Medical University
Brunner, JS, et al. (2020) The PI3K pathway maintains metabolic health by taking MARCO-dependent lipids through macrophages in adipose tissue. Nature’s Metabolism. doi.org/10.1038/s42255-020-00311-5.