Immunometabolic cues guiding adipose tissue remodeling in cachexia
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.
Martina Schweiger
Institute of Molecular Biosciences
Heinrichstraße 31
8010 Graz, Austria
tina.schweiger@uni-graz.at
Forschungsportal – Schweiger Martina- Karl-Franzens-Universität Graz
Project Members
Sophia Chrysostomou
PhD student
SFB member
Isabella Pototschnig
PhD student
SFB affiliated
Thomas Rauchenwald
PhD student
SFB member
Michaela Lang
Postdoctoral Researcher
Internal Member
Research Publications
Robust dual-angle T1 measurement in magnetization transfer spectroscopy by time-optimal control. Graf C, Stollberger R, Rund A, Schweiger M, Diwoky C. NMR Biomed. 2024 Apr 7:e5151. doi: 10.1002/nbm.5151. https://doi.org/10.1002/nbm.5151
Probiotic OMNi-BiOTiC® 10 AAD Reduces Cyclophosphamide-Induced Inflammation and Adipose Tissue Wasting in Mice. Obermüller B, Singer G, Kienesberger B, Mittl B, Stadlbauer V, Horvath A, Miekisch W, Fuchs P, Schweiger M, Pajed L, Till H, Castellani C. Nutrients. 2023 Aug 20;15(16):3655. doi: 10.3390/nu15163655. https://doi.org/10.3390/nu15163655
R-ketorolac ameliorates cancer-associated cachexia and prolongs survival of tumour-bearing mice. Chrysostomou SE, Eder S, Pototschnig I, Mayer AL, Derler M, Mussbacher M, Schauer S, Zhang D, Yan D, Liu G, Hoefler G, Weichhart T, Vesely PW, Zhang L, Schweiger* M. J Cachexia Sarcopenia Muscle. 2024 Feb 1. doi: 10.1002/jcsm.13422. https://doi.org/10.1002/jcsm.13422.
Interleukin-6 initiates muscle- and adipose tissue wasting in a novel C57BL/6 model of cancer-associated cachexia. Pototschnig I, Feiler U, Diwoky C, Vesely PW, Rauchenwald T, Paar M, Bakiri L, Pajed L, Hofer P, Kashofer K, Sukhbaatar N, Schoiswohl G, Weichhart T, Hoefler G, Bock C, Pichler M, Wagner EF, Zechner R, Schweiger M*. J Cachexia Sarcopenia Muscle. 2023 Feb;14(1):93-107. doi: 10.1002/jcsm.13109. https://doi.org/10.1002/jcsm.13109.
Adipose triglyceride lipase-mediated lipid catabolism is essential for bronchiolar regeneration. Kanti MM, Striessnig-Bina I, Wieser BI, Schauer S, Leitinger G, Eichmann TO, Schweiger M, Winkler M, Winter E, Lana A, Kufferath I, Marsh LM, Kwapiszewska G, Zechner R, Hoefler G, Vesely PW. JCI Insight. 2022 May 9;7(9):e149438. doi: 10.1172/jci.insight.149438. 10.1172/jci.insight.149438
An immune-sympathetic neuron communication axis guides adipose tissue browning in cancer-associated cachexia. Xie H, Heier C, Meng X, Bakiri L, Pototschnig I, Tang Z, Schauer S, Baumgartner VJ, Grabner GF, Schabbauer G, Wolinski H, Robertson GR, Hoefler G, Zeng W, Wagner EF, Schweiger M*, Zechner R. Proc Natl Acad Sci U S A. 2022 Mar 1;119(9):e2112840119. doi: 10.1073/pnas.2112840119. https://doi.org/10.1073/pnas.2112840119.
Lipolysis: cellular mechanisms for lipid mobilization from fat stores. Grabner GF, Xie H, Schweiger M*, Zechner R*. Nat Metab. 2021 Nov;3(11):1445-1465. DOI:10.1038/s42255-021-00493-6. *SFB-PI corresponding authors https://www.nature.com/articles/s42255-021-00493-6.