A5025421377- Lipid metabolism and biosynthesis
- Adipose Tissue and Metabolism
- Liver Disease Diagnosis and Treatment
- Endoplasmic Reticulum Stress and Disease
- Diet, Metabolism, and Disease
- Pancreatic function and diabetes
- Drug Transport and Resistance Mechanisms
- Cannabis and Cannabinoid Research
- Liver Disease and Transplantation
- Enzyme Catalysis and Immobilization
- Peroxisome Proliferator-Activated Receptors
- Diet and metabolism studies
- Cerebrovascular and Carotid Artery Diseases
- Fatty Acid Research and Health
- Eicosanoids and Hypertension Pharmacology
- Clinical Nutrition and Gastroenterology
- Electronic Health Records Systems
- Hemodynamic Monitoring and Therapy
- Metabolism, Diabetes, and Cancer
- Cellular transport and secretion
- Renal function and acid-base balance
- Medical and Health Sciences Research
- High Altitude and Hypoxia
- Pain Management and Treatment
- Liver Diseases and Immunity
Medical University of Graz
2024-2025
University of Graz
2015-2024
BioTechMed-Graz
2017
Institute of Organic Chemistry
2017
Shura Council
2015
Knowledge Unlatched (Germany)
2015
Graz University of Technology
2000
University of Vienna
1975
Hôpital Beaujon
1971
Medical University of Vienna
1971
Abstract Elevated circulating fatty acids (FAs) contribute to the development of obesity-associated metabolic complications such as insulin resistance (IR) and non-alcoholic liver disease (NAFLD). Hence, reducing adipose tissue lipolysis diminish mobilization FAs lower their respective plasma concentrations represents a potential treatment strategy counteract disorders. Here we show that specific inhibition triglyceride lipase (Atgl) with chemical inhibitor, Atglistatin, effectively reduces...
Cardiac triacylglycerol (TG) catabolism critically depends on the TG hydrolytic activity of adipose triglyceride lipase (ATGL). Perilipin 5 (Plin5) is expressed in cardiac muscle (CM) and has been shown to interact with ATGL its coactivator comparative gene identification-58 (CGI-58). Furthermore, ectopic Plin5 expression increases cellular content Plin5-deficient mice exhibit reduced levels. In this study we show that muscle-specific overexpression perilipin (CM-Plin5) massively accumulate...
The hypothalamus of hypercaloric diet-induced obese animals is featured by a significant increase microglial reactivity and its associated cytokine production. However, the role dietary components, in particular fat carbohydrate, with respect to hypothalamic inflammatory response consequent impact on control energy homeostasis yet not clear. We dissected different effects high-carbohydrate high-fat (HCHF) diets low-carbohydrate (LCHF) responses neurons non-neuronal cells tested hypothesis...
Cancer-associated cachexia (CAC) is a hypermetabolic syndrome characterized by unintended weight loss due to the atrophy of adipose tissue and skeletal muscle. A phenotypic switch from white beige adipocytes, phenomenon called browning, accelerates CAC increasing dissipation energy as heat. Addressing mechanisms (WAT) browning in CAC, we now show that cachexigenic tumors activate type 2 immunity cachectic WAT, generating neuroprotective environment increases peripheral sympathetic activity....
Elaborate control mechanisms of intracellular triacylglycerol (TAG) breakdown are critically involved in the maintenance energy homeostasis. Hypoxia-inducible lipid droplet-associated protein (HILPDA)/hypoxia-inducible gene-2 (Hig-2) has been shown to affect TAG levels, yet, underlying molecular unclear. Here, we show that HILPDA inhibits adipose triglyceride lipase (ATGL), enzyme catalyzing first step hydrolysis. shares structural similarity with G0/G1 switch gene 2 (G0S2), an established...
Monoglyceride lipase (MGL) is required for efficient hydrolysis of the endocannabinoid 2-arachidonoylglyerol (2-AG) in brain generating arachidonic acid (AA) and glycerol. This metabolic function makes MGL an interesting target treatment neuroinflammation, since 2-AG exhibits anti-inflammatory properties AA a precursor pro-inflammatory prostaglandins. Astrocytes are important source 2-AG, highly express MGL. In present study, we dissected distinct contribution astrocytes on metabolism by...
Chronically elevated circulating fatty acid levels promote lipid accumulation in nonadipose tissues and cause lipotoxicity. Adipose triglyceride lipase (ATGL) critically determines the release of acids from white adipose tissue, accumulating evidence suggests that inactivation ATGL has beneficial effects on lipotoxicity-driven disorders including insulin resistance, steatohepatitis, heart disease, classifying as a promising drug target. Here, we report development biological characterization...
Hepatic stellate cells (HSCs) store triglycerides (TGs) and retinyl ester (RE) in cytosolic lipid droplets. RE stores are degraded following retinoid starvation or response to pathogenic stimuli resulting HSC activation. At present, the major enzymes catalyzing degradation HSCs unknown. In this study, we investigated whether adipose triglyceride lipase (ATGL) is involved catabolism of HSCs. Additionally, compared effects ATGL deficiency hormone-sensitive (HSL) deficiency, a known hydrolase...
<h3>Background & Aims</h3> Adipose tissue (AT)-derived fatty acids (FAs) are utilized for hepatic triacylglycerol (TG) generation upon fasting. However, their potential impact as signaling molecules is not established. Herein we examined the role of exogenous AT-derived FAs in regulation gene expression by investigating mice with a defect FA supply to liver. <h3>Methods</h3> Plasma levels, TG hydrolytic activities and lipid content were determined lacking lipase co-activator comparative...
Bis(monoacylglycerol)phosphate (BMP) is a phospholipid that crucial for lipid degradation and sorting in acidic organelles. Genetic drug-induced lysosomal storage disorders (LSDs) are associated with increased BMP concentrations tissues the circulation. Data on other than LSDs, however, scarce, key enzymes regulating metabolism remain elusive. Here, we demonstrate common metabolic intracellular hydrolase α/β-hydrolase domain-containing 6 (ABHD6) affect mice humans. In mice, dietary overload...
Heart failure (HF) is characterized by an overactivation of β-adrenergic signalling that directly contributes to impairment myocardial function. Moreover, induces adipose tissue lipolysis, which may further worsen the development HF. Recently, we demonstrated tissue-specific deletion triglyceride lipase (ATGL) prevents pressure-mediated HF in mice. In this study, investigated cardioprotective effects a new pharmacological inhibitor ATGL, Atglistatin, predominantly targeting ATGL tissue, on...
Lysosomal acid lipase (LAL) is the key enzyme, which degrades neutral lipids at an acidic pH in lysosomes. The role of LAL various cellular processes has mostly been studied LAL-knockout mice, share phenotypical characteristics with humans suffering from deficiency. In vitro, cell-specific functions have commonly investigated by using inhibitors Lalistat-1 and Lalistat-2. We performed lipid hydrolase activity assays serine hydrolase-specific activity-based labeling combined quantitative...
Abstract ATGL is a key enzyme in intracellular lipolysis and plays an important role metabolic cardiovascular diseases. tightly regulated by known set of protein-protein interaction partners with activating or inhibiting functions the control lipolysis. Here, we use deep mutational protein perturbation scanning generate comprehensive profiles single amino acid variants that affect interactions its regulatory partners: CGI-58, G0S2, PLIN1, PLIN5 CIDEC. Twenty-three yield specific pattern when...
Bis(monoacylglycero)phosphate (BMP) is a major phospholipid constituent of intralumenal membranes in late endosomes/lysosomes, where it regulates the degradation and sorting lipid cargo. Recent observations suggest that Batten disease-associated protein CLN5 functions as lysosomal BMP synthase. Here, we show transacylation reactions catalyzed by cytosolic secreted enzymes enhance synthesis independently CLN5. The transacylases identified this study are capable acylating precursor...
Adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) are limiting in cellular catabolism. Although ATGL deficiency is compatible with normal skin development, mice globally lacking CGI-58 die postnatally exhibit a severe epidermal permeability barrier defect, which may originate from and/or peripheral changes lipid energy metabolism. Here, we show that epidermis-specific disruption of sufficient to provoke defect the formation functional...
Monoacylglycerol lipase (MGL) is the rate-limiting enzyme in degradation of monoacylglycerols. To examine role MGL hepatic steatosis, WT and KO (MGL−/−) mice were challenged with a Western diet (WD) over 12 weeks. Lipid metabolism, inflammation, fibrosis assessed by serum biochemistry, histology, gene-expression profiling liver adipose depots. Intestinal fat absorption was measured gas chromatography. Primary adipocyte 3T3-L1 cells analyzed flow cytometry blot. Human hepatocytes treated...
Abstract Bis(monoacylglycero)phosphate (BMP) is a major phospholipid constituent of intralumenal membranes in late endosomes/lysosomes, where it regulates the degradation and sorting lipid cargo. Recent observations suggest that Batten disease - associated protein CLN5 functions as lysosomal BMP synthase. Here, we show transacylation reactions catalyzed by cytosolic secreted enzymes enhance synthesis independently CLN5. The transacylases identified this study are capable acylating precursor...
White adipose tissue (WAT) comprises a plethora of cell types beyond adipocytes forming regulatory network that ensures systemic energy homeostasis. Intertissue communication is facilitated by metabolites and signaling molecules are spread vasculature nerves. Previous works indicated WAT responds to environmental cues adapting the abundance these “communication routes”, however, high intra-tissue heterogeneity questions informative value bulk or single analyses underscores necessity...
Monoglyceride lipase (MGL) degrades 2-arachidonoyl glycerol (2-AG), an endogenous agonist of cannabinoid receptors (CB1/2 ). Because the CB1 receptor is involved in control gut function, we investigated effects pharmacological inhibition and genetic deletion MGL on intestinal motility. Furthermore, determined whether defective 2-AG degradation affects μ-opioid (μ receptor) signalling, a parallel pathway regulating motility.Gut motility was by monitoring Evans Blue transit colonic bead...