A5049644118- Lipid metabolism and biosynthesis
- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- Lipid metabolism and disorders
- Cholesterol and Lipid Metabolism
- Lysosomal Storage Disorders Research
- Peroxisome Proliferator-Activated Receptors
- Calcium signaling and nucleotide metabolism
- Liver Disease Diagnosis and Treatment
- Sphingolipid Metabolism and Signaling
- Diet, Metabolism, and Disease
- Adipokines, Inflammation, and Metabolic Diseases
- Cancer, Lipids, and Metabolism
- Autophagy in Disease and Therapy
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Diet and metabolism studies
- Cannabis and Cannabinoid Research
- Endoplasmic Reticulum Stress and Disease
- Metabolism, Diabetes, and Cancer
- Metabolomics and Mass Spectrometry Studies
- Folate and B Vitamins Research
- Drug Transport and Resistance Mechanisms
- Phagocytosis and Immune Regulation
- Epigenetics and DNA Methylation
- Cardiovascular Disease and Adiposity
Medical University of Graz
2016-2025
BioTechMed-Graz
2016-2024
Institut Necker Enfants Malades
2024
University of Graz
1999-2023
Graz University of Technology
2023
Fujian Medical University
2022
Institute of Molecular Biology
2001-2016
Yale University
2010
University of Bergamo
2010
Leiden University
2010
Fat tissue is the most important energy depot in vertebrates. The release of free fatty acids (FFAs) from stored fat requires enzymatic activity lipases. We showed that genetic inactivation adipose triglyceride lipase (ATGL) mice increases mass and leads to triacylglycerol deposition multiple tissues. ATGL-deficient accumulated large amounts lipid heart, causing cardiac dysfunction premature death. Defective cold adaptation indicated enzyme provides FFAs fuel thermogenesis. reduced...
Changes in intra- and extracellular potassium ion (K+) concentrations control many important cellular processes related biological functions. However, our current understanding of the spatiotemporal patterns physiological pathological K+ changes is severely limited by lack practicable detection methods. We developed K+-sensitive genetically encoded, Förster resonance energy transfer-(FRET) based probes, called GEPIIs, which enable quantitative real-time imaging dynamics. GEPIIs as purified...
Growth hormone (GH)-activated signal transducer and activator of transcription 5 (STAT5) the glucocorticoid (GC)-responsive receptor (GR) are important integrators in liver during metabolic physiologic stress. Their deregulation has been implicated development diseases, such as steatosis progression to fibrosis. Using liver-specific STAT5 GR knockout mice, we addressed their role metabolism cancer onset. single STAT5/GR double mutants developed steatosis, but only double-mutant mice...
Macrophages face a substantial amount of cholesterol after the ingestion apoptotic cells, and LIPA (lysosomal acid lipase) has major role in hydrolyzing cholesteryl esters endocytic compartment.Here, we directly investigated LIPA-mediated clearance cells both vitro vivo.We show that inhibition causes defective efferocytic response because impaired generation 25-hydroxycholesterol 27-hydroxycholesterol. Reduced synthesis contributed to mitochondria-associated membrane leading mitochondrial...
Microglia, the immunocompetent cells of CNS, rapidly respond to brain injury and disease by altering their morphology phenotype adopt an activated state. Microglia can exist broadly between two different states, namely classical (M1) alternative (M2) phenotype. The first is characterized production pro-inflammatory cytokines/chemokines reactive oxygen and/or nitrogen species. In contrast, alternatively microglia are typified anti-inflammatory supporting wound healing debris clearance....
The known link between obesity and cancer suggests an important interaction the host lipid metabolism tumorigenesis. Here, we used a syngeneic tumor graft model to demonstrate that development influences metabolism. BCR-Abl-transformed precursor B cell tumors induced hyperlipidemia by stimulating very low-density lipoprotein (VLDL) production blunting VLDL (LDL) turnover. To assess whether progression was dependent on tumor-induced hyperlipidemia, utilized production-deficient mouse model,...
In obesity, sustained adipose tissue (AT) inflammation constitutes a cellular memory that limits the effectiveness of weight loss interventions. Yet, impact fasting regimens on regulation AT immune infiltration is still elusive. Here we show intermittent (IF) exacerbates lipid-associated macrophage (LAM) inflammatory phenotype visceral in obese mice. Importantly, this increase LAM abundance strongly p53 dependent and partly mediated by p53-driven adipocyte apoptosis. Adipocyte-specific...
Liver X receptors (LXRs) are important regulators of cholesterol and lipid metabolism. LXR agonists have been shown to limit the cellular content by inducing reverse transport, increasing bile acid production, inhibiting intestinal absorption. Most them, however, also increase lipogenesis via sterol regulatory element-binding protein-1c (SREBP1c) carbohydrate response protein activation resulting in hypertriglyceridemia liver steatosis. We report on antiatherogenic properties steroidal...
High plasma concentrations of lipoprotein(a) [Lp(a), which is encoded by the APOA gene] increase an individual's risk developing diseases, such as coronary artery restenosis, and stroke. Unfortunately, increased Lp(a) levels are minimally influenced dietary changes or drug treatment. Further, development Lp(a)-specific medications has been hampered limited knowledge metabolism. In this study, we identified patients suffering from biliary obstructions with very low that rise substantially...
Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme mediating (TG) hydrolysis. The lack of ATGL results in TG accumulation multiple tissues, underscoring critical role maintaining lipid homeostasis. Recent evidence suggests that affects metabolism via activation peroxisome proliferator-activated receptor α (PPARα). To investigate specific effects intestinal on we generated mice lacking exclusively intestine (ATGLiKO). We found decreased hydrolase activity and increased...
In humans, mutations in ATGL lead to TG accumulation LDs of most tissues and cells, including peripheral blood leukocytes. This pathologic condition is called Jordans' anomaly, which functional consequences have not been investigated. the present study, we tested hypothesis that plays a role leukocyte LD metabolism immune cell function. Similar humans with loss-of-function ATGL, found global myeloid-specific Atgl(-/-) mice exhibit anomaly increased abundance intracellular TG-rich neutrophil...
Peripheral leukocytes can exacerbate brain damage by release of cytotoxic mediators that disrupt blood-brain barrier (BBB) function. One the oxidants released activated is hypochlorous acid (HOCl) formed via myeloperoxidase (MPO)-H2O2-Cl(-) system. In present study we examined role leukocyte activation, leukocyte-derived MPO and MPO-generated on BBB function in vitro vivo. a mouse model lipopolysaccharide (LPS)-induced systemic inflammation, neutrophils had become adherent into...
Programmed cell death of lipid-laden macrophages is a prominent feature atherosclerotic lesions and mostly ascribed to accumulation excess intracellular cholesterol. The present in vitro study investigated whether triacylglycerol (TG) could activate similar apoptotic response macrophages. To address this question, we utilized peritoneal isolated from mice lacking adipose triglyceride lipase (ATGL), the major enzyme responsible for TG hydrolysis multiple tissues. In Atgl(-/-) macrophages,...
Prostaglandin (PG) D2 is an early-phase mediator in inflammation, but its action and the roles of 2 D-type prostanoid receptors (DPs) DP1 DP2 (also called chemoattractant receptor-homologous molecule expressed on T(H)2 cells) regulating macrophages have not been elucidated to date.We investigated role PGD2 primary human macrophages, as well murine lung their ability influence neutrophil vitro vivo.In studies, including migration, Ca(2+) flux, cytokine secretion, were conducted with...
Aberrant insulin signaling constitutes an early change in Alzheimer's disease (AD). Insulin receptors (IR) and low-density lipoprotein receptor-related protein-1 (LRP-1) are expressed brain capillary endothelial cells (BCEC) forming the blood-brain barrier (BBB). There, may regulate function of LRP-1 Aβ clearance from brain. Changes IR-β at BBB AD not well understood. Herein, we identified a reduction cerebral cerebrovascular levels 9-month-old male female 3XTg-AD (PS1M146V, APPSwe,...
// Stefanie Schlager 1,2 , Nemanja Vujic 1 Melanie Korbelius Madalina Duta-Mare Juliane Dorow 3,4 Christina Leopold Silvia Rainer Martin Wegscheider Helga Reicher Uta Ceglarek Wolfgang Sattler 1,5 Branislav Radovic and Dagmar Kratky Institute of Molecular Biology Biochemistry, Medical University Graz, Austria 2 Boehringer Ingelheim, Vienna, 3 Laboratory Medicine, Clinical Chemistry Diagnostics, Hospital Leipzig, Germany 4 LIFE-Leipzig Research Center for Civilization Diseases, 5...
The dysregulation of cellular metabolism is a hallmark ageing. To understand the metabolic changes that occur as consequence ageing process and to find biomarkers for age-related diseases, we conducted metabolomic analyses brain, heart, kidney, liver, lung spleen in young (9-10 weeks) old (96-104 wild-type mice [mixed genetic background 129/J C57BL/6] using NMR spectroscopy. We found differences fingerprints all tissues distinguished several metabolites be altered most tissues, suggesting...
Quantitative information about the levels and dynamics of post-translational modifications (PTMs) is critical for an understanding cellular functions. Protein arginine methylation (ArgMet) important subclass PTMs involved in a plethora (patho)physiological processes. However, because lack methods global analysis ArgMet, link between ArgMet levels, dynamics, (patho)physiology remains largely unknown. We utilized high sensitivity robustness nuclear magnetic resonance (NMR) spectroscopy to...