Lipid buffering macrophages in adipose tissue
In this sub-project we want to analyze the important contribution of the macrophage PI3K signaling pathway to metabolic health in the adipose tissue. We propose that distinct lipid-buffering adipose tissue macrophages rely on metabolites, which shape their epigenetic landscape. We contribute to the SFB by providing the consortium with a variety of fate mapping and reporter mouse lines (T. Weichhart, M. Schweiger, E. Pohl, G. Egger, A. Haschemi, C. Moissl-Eichinger). We will generate macrophage data from the adipose tissue in different models of obesity and their associated analyses (E. Pohl, G. Egger, A. Haschemi). Furthermore, we will provide the samples from obese and respective lean mice for the analyses of the microbiome. Differences in the microbiota concerning “healthy obese” versus “sick obese” may influence various aspects of adipose tissue function (C. Moissl-Eichinger). Crosstalk of murine and human adipose tissue macrophages with the stromal vascular fraction will be analyzed in co-culture models and 3D-organoids (M. Schweiger). Together with members of the consortium we will decipher the contribution of metabolic pathways such as one carbon metabolism, fatty acid oxidation and TCA cycle to epigenetic programming of beneficial adipose tissue macrophages (A. Haschemi, T. Weichhart, M. Schweiger, E. Pohl, G. Egger).
Gernot Schabbauer
Medical University of Vienna
Center for Physiology and Pharmacology
Institute for Vascular Biology and Thrombosis Research
Schwarzspanierstrasse 17
1090 Vienna
gernot.schabbauer@meduniwien.ac.at
https://www.meduniwien.ac.at/hp/index.php?id=13771&res_id=98&name= Gernot_Schabbauer
Project Members
Anja Dobrijević
PhD Student
SFB Member
Jasmin Wächter
PhD Student
SFB Member
Research Publications
Metabolic support by macrophages sustains colonic epithelial homeostasis. Fritsch SD, Sukhbaatar N, Gonzales K, Sahu A, Tran L, Vogel A, Mazic M, Wilson JL, Forisch S, Mayr H, Oberle R, Weiszmann J, Brenner M, Vanhoutte R, Hofmann M, Pirnes-Karhu S, Magnes C, Kühnast T, Weckwerth W, Bock C, Klavins K, Hengstschläger M, Moissl-Eichinger C, Schabbauer G, Egger G, Pirinen E, Verhelst SHL, Weichhart T. Cell Metab. 2023 Nov 7;35(11):1931-1943.e8. https://doi.org/10.1016/j.cmet.2023.09.010.
Metabolic rewiring promotes anti-inflammatory effects of glucocorticoids. Auger JP, Zimmermann M, Faas M, Stifel U, Chambers D, Krishnacoumar B, Taudte RV, Grund C, Erdmann G, Scholtysek C, Uderhardt S, Ben Brahim O, Pascual Maté M, Stoll C, Böttcher M, Palumbo-Zerr K, Mangan MSJ, Dzamukova M, Kieler M, Hofmann M, Blüml S, Schabbauer G, Mougiakakos D, Sonnewald U, Hartmann F, Simon D, Kleyer A, Grüneboom A, Finotto S, Latz E, Hofmann J, Schett G, Tuckermann J, Krönke G. Nature. 2024 Apr 10. https://doi.org/10.1038/s41586-024-07282-7.
The PI3K pathway preserves metabolic health through MARCO-dependent lipid uptake by adipose tissue macrophages. Brunner JS, Vogel A, Lercher A, Caldera M, Korosec A, Pühringer M, Hofmann M, Hajto A, Kieler M, Garrido LQ, Kerndl M, Kuttke M, Mesteri I, Górna MW, Kulik M, Dominiak PM, Brandon AE, Estevez E, Egan CL, Gruber F, Schweiger M, Menche J, Bergthaler A, Weichhart T, Klavins K, Febbraio MA, Sharif O, Schabbauer G. Nat Metab. 2020 Dec;2(12):1427-1442. https://doi.org/10.1038/s42255-020-00311-5.
JAK1 signaling in dendritic cells promotes peripheral tolerance in autoimmunity through PD-L1-mediated regulatory T cell induction. Vogel A, Martin K, Soukup K, Halfmann A, Kerndl M, Brunner JS, Hofmann M, Oberbichler L, Korosec A, Kuttke M, Datler H, Kieler M, Musiejovsky L, Dohnal A, Sharif O, Schabbauer G. Cell Rep. 2022 Feb 22;38(8):110420. https://doi.org/10.1016/j.celrep.2022.110420.
Lipid scavenging macrophages and inflammation. Vogel A, Brunner JS, Hajto A, Sharif O, Schabbauer G. Biochim Biophys Acta Mol Cell Biol Lipids. 2022 Jan;1867(1):159066. https://doi.org/10.1016/j.bbalip.2021.159066.