Selected Metabolomics and Lipidomics projects highlighting our expertise
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Metabolic fluxes in lung tumors

Core Facility Mass Spectrometry (MUG)  in collaboration with Katharina Leithner, Medizinische Universität Graz

This study shows for the first time the involvement of the mitochondrial phosphoenolpyruvate carboxykinase (PCK2) in utilization of lactate as gluconeogenesis substrate for tumor cell growth in a glucose depleted local cell environment. By feeding of stable isotope labeled lactate and subsequent mass spectrometric determination of upstream metabolites like phosphoenol pyruvate, glyceraldehyde phosphate and 3-phosphoglycerate we could trace the metabolic flux of this substrate in central metabolism and pinpoint the role of PCK2.

Leithner et al., 2015 Oncogene in press

 

Clinical tracer studies in diabetes research

Core Facility Mass Spectrometry (MUG) in collaboration with Werner Regittnig, Medizinische Universität Graz, within the EU-Project PCDiab (www.pcdiab.eu/)

Clinical trials in diabetes research often encompass mass spectrometric measurement of stable isotope labeled tracer compounds infused in humans for determination of metabolic fluxes and turnover rates. Since literature known methods for determination of glucose tracers are either cumbersome or unreliable, we developed a highly accurate and fast method which capitalizes on the high resolving power of our mass spectrometric equipment coupled to a custom tailored high end chromatography and a dedicated data processing algorithm. The method is currently applied for a clinical trial in diabetes research.

Triebl et al., manuscript in preparation

 

Biomarkers for liver steatosis and insulin resistance

Core Facility Mass Spectrometry (MUG)  in collaboration with Friedrich Spener, Medizinische Universität Graz

In this project a global LC-MS/MS based lipidomic profiling approach of hepatic lipid droplets from mouse models under genetic stress (ATGL ko) or nutritional stress (high fat diet, fasting)  led to discovery of selective biomarker compounds for high fat diet induced liver steatosis with insulin resistance. These marker compounds were singled out to be triglycerides containing essentially palmitic, stearic, oleic and arachidic acid.

Chitraju et al., 2012 J Lipid Res 53:2141-52

Chitraju et al., 2013 J Lipid Res 54:2185-94

Hartler et al., 2014 Sci Data in press

 

Selective autophagy of peroxisomes, cancer development and lipid homeostasis

Core Facility Mass Spectrometry (MUG)  in collaboration with Werner Kovacs, ETH Zürich

This study establishes for the first time the link between hypoxia-inducible factors alpha (HIF-α), selective autophagy of peroxisomes (pexophagy) and metabolism. The impact of HIF-α signaling on peroxisomes in liver-specific Vhl, Vhl/Hif1α, and Vhl/Hif2α knockout mice was investigated. Hif-2a activation leads to changes in the lipid profile as determined by our high resolution LC-MS/MS platform. Particularly interesting, this study shows that upregulation of HIF-2α decreases peroxisome abundance by increased pexophagy and concomitant changes in the lipid profile reminiscent of peroxisomal disorders are strongly correlated with growth and development of tumors. Hence profiling of specific lipids like plasmalogens and very long-chain fatty acids could prove of high diagnostic value for certain tumors.

Walter et al., 2014 Cell Metabolism 20 (5):882-897

 

Identification of a novel therapeutic target for metabolic syndrome

Core Facility Mass Spectrometry (MUG)  in collaboration with Christian Wolfrum, ETH Zürich

In this so far unpublished high potential study we pinpointed a high affinity ligand for RORγ by a non-targeted metabolomics approach, based on ultra-high resolution LC-MS. Since RORγ activity determines the differentiation of preadipocytes into either adipocyte hypertrophy (bad fat; metabolic syndrome) or adipocyte hyperplasia (good fat; no metabolic syndrome) the activity status of this orphan receptor is a powerful switch in the development of metabolic syndrome and insulin resistance in type 2 diabetes.

 

Signaling pathways in neurobiology

Core Facility Mass Spectrometry (MUG)  in collaboration with Ueli Suter, ETH Zürich

This project discovered the dependency of myelination in the central and the peripheral nervous system (CNS & PNS) on mTORC1 and its associated pathways in mouse models. During the course of this project determination of lipid profiles by our high resolution lipidomics platform was crucial because myelination is a highly lipid dependent process. Therefore aberrant signaling processes lead to myelination defects with highly phospho- and sphingolipid dependent phenotypes. The lipidomic analysis for this project was highly demanding because preparation of nerves free of other tissue is extremely challenging and resulted only in minimal quantities of nerve tissue for mass spectrometric determination.

Lebrun et al., 2014 J Neurosci 25:8432-48

Norrmen et al., 2014 Cell Reports 9:646-660