Mitochondrial UCP2 and the metabolic flexibility of adipose tissue macrophages


In this sub-project, we will focus on the role of mitochondria in the maintenance of adipose tissue homeostasis. We aim to understand the molecular mechanisms underlying the involvement of the mitochondrial uncoupling protein (UCP2) in the metabolic flexibility of macrophages associated with adipose tissue (ATMs). We will investigate a novel concept of metabolism-dependent UCP2 expression in murine and human macrophages (T. Weichhart, G. Schabbauer), using specific antibodies designed in our laboratories. To explore the metabolic crosstalk of macrophages with adipose tissue, we will compare signals derived from lean, obese, fasting, and cachectic AT states (M. Schweiger) with respect to their ability to induce UCP2 expression in ATMs simultaneously to the metabolic changes. The latter will be investigated using omics approaches, enzyme histochemistry in situ (A. Haschemi), and extracellular flux analysis (Seahorse®). We will evaluate whether macrophages regulate the inflammatory process by UCP2-mediated modulation of glutamine and/or FA metabolism using genetic mouse models (T. Weichhart, G. Schabbauer, M. Schweiger), adipose tissue -organoids (M. Schweiger), and human tissues (G. Egger). We will also explore the function of UCP2 in wild-type and gene-modified macrophages in vivo in adipose tissue organoids using two-photon microscopy and Spot-tagged UCP2. We want to shed light in the understanding of the mechanistic aspects of UCP2 function in macrophages, which may constitute a novel immunometabolic target in human disease.

Elena Pohl

University of Veterinary Medicine Vienna
Institute of Physiology, Pathophysiology and Biophysics
Veterinaerplatz 1
1210 Vienna

elena.pohl@vetmeduni.ac.at
https://www.vetmeduni.ac.at/en/biophysics


Project Members

Felix Locker
Postdoc
SFB Member

Taraneh Beikbaghban
PhD Student
SFB Member


A Special Research Program funded by the Austrian Science Fund

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1090 Vienna, Austria
sfb_immunomet@meduniwien.ac.at
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