The study identifies a new factor that offers a potential strategy for treating obesity

Reviewed by Emily Henderson, B.Sc.November 17, 2020

Obesity is a serious global health problem and a risk factor for diseases such as type II diabetes, heart disease and fatty liver disease. A central element in the development of obesity is adipose tissue, which includes adipose cells (the so-called adipocytes, which are specialized for storing fat) and macrophages (scavenger cells of the immune system, which are typically associated with the destruction of microbes).

Together with researchers from Poland, Germany, Australia and Austria, a team of scientists from MedUni Vienna has now discovered the signaling pathways responsible for the development of a valuable type of adipose tissue macrophage (ATM) in obesity, which prevents lipotoxicity. . Lipotoxicity is the process by which fat molecules are deposited in non-adipose tissues. This study has now been published in the main journal Metabolism of nature.

In this study, researchers, including some from CeMM (Research Center for Molecular Medicine of the Austrian Academy of Sciences) and the University of Graz, specifically investigated the PI3K signaling pathway. This is an important metabolic regulator, as it regulates the accumulation of fat and plays an important role in the cellular reaction to the hormone insulin. In obesity, decreased insulin action or insulin resistance leads to type II diabetes, which is linked to high blood glucose levels.

Gernot Schabbauer from the Institute of Vascular Biology and Thrombosis Research at the Center for Physiology and Pharmacology of MedUni Vienna and senior author of the study has been studying the PI3K signaling pathway in immune cells for several years: “The key role of PI3K in metabolic processes is proven but its role in adipose tissue macrophages was unclear until now. “Julia Brunner, lead co-author of the study, adds:” ATMs are like Dr. Jekyll and Mr. Hyde – in obesity they can be good We hypothesized that an active PI3K signaling pathway could tip the scales in favor of “good.”

Using techniques such as multicolor flow cytometry, lipidomics, cellular respiration tests and several animal models, the scientists found that sustained activity of the PI3K signaling pathway can tip the balance within macrophages for the better: this produces in particular specialized TMJs, which are characterized by an increased number of MARCO scavenger receptors (receptor for macrophages with collagen structure) on their surface.

We have found that these ATMs expressing MARCO are professional lipid scavengers. These cells absorb fat in a MARCO-dependent manner and break it down, thus preventing it from finding its way into the bloodstream. “

Andrea Vogel, co-lead author of the study and PhD candidate in immunology at MedUni Vienna

Omar Sharif, senior co-author of the study, adds: “Metabolic syndrome and lipotoxicity are characteristic features of obesity. Our work indicates that higher lipid intake and improved energy metabolism of TMJs help maintain systemic metabolic health. . This can have -to-reach impacts for a range of metabolic diseases. “

Subsequent studies will now be conducted to establish whether PI3K signaling can also have a lasting influence on the TMJ population in humans as well. “Although moderate PI3K inhibition has already been discussed as a therapeutic strategy for the treatment of metabolic diseases, our data indicate potential unexpected side effects. These could include altered blood lipid levels, caused by the reduced fat uptake of TMJs.” says Schabbauer.