In this sub-project we aim to characterize the immunometabolic network, and how it contributes to adipose tissue remodeling in cachexia. A prolonged negative energy balance results in adipose tissue remodeling characterized by transient inflammation, increased innervation and the appearance of catabolic beige adipocytes. Under pathophysiological hypermetabolic conditions like cachexia, remodeling towards beige adipose tissue amplifies the sustained catabolic signal generating a vicious spiral towards complete loss of adipose tissue, muscle tissue, and death. However, the mechanisms of catabolic adipose tissue browning are not understood. Therefore, we will compare adipose tissue phenotypes of healthy mice and humans with mice and patients suffering cancer-associated cachexia. Together with E. Pohl, A. Haschemi, G. Egger, and T. Weichhart we will phenotypically and metabolically explore the immunometabolic profile of macrophage populations in vivo. Using genetic models (together with T. Weichhart and G. Schabbauer) we will identify immunometabolic signals, their sources (like the microbiome, together with C. Moissl-Eichinger), and how they facilitate communication between adipocytes, neurons, and macrophages in AT. Spheroid cultures of murine and human cells will be used to delineate whether cells directly communicate, identify the signals, and test their ability to reproduce in vivo findings. Unraveling the signals that trigger adipose tissue remodeling, may lead to novel therapeutic strategies for cachexia treatment.
Institute of Molecular Biosciences
8010 Graz, Austria
Forschungsportal – Schweiger Martina- Karl-Franzens-Universität Graz