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Rudolf Zechner

Ursula Feiler: Identification of cachexia-inducing factors
Pia Benedikt: Investigating the molecular mechanisms driving adipose and muscle wasting in cancer associated cachexia

Closed projects
Petra Kienesberger: Identification of a novel patatin-like lysolecithine lipase
Renate Schreiber: Lipases and their function in energy homoestasis and metabolic diseases
Manju Kumari: Lipases and Lipotoxocity
Thomas Eichmann: The Lipid Lowering Effect of Nicotinic Acid
Chandramohan Chitraju: Cellular Triacylglycerol Lipases and Lipoprotein Metabolism
Petra Kotzbeck: The crosstalk between lipolysis and adipokines
Susanne Grond: The role of lipid hydrolases in lipid and energy metabolism
Peter Hofer: Molecular characterization of the lipolysome
Lukas Grumet: "Lipases of hepatic stellate cells"
Hao Xie: Molecular mechanisms that regulate lipolysis in cancer cachexia

Further Information
Curriculum Vitae (44 kB)
Publication List (external Link)
Collaborators (45 kB)
Grants (56 kB)


Rudolf Zechner
Institute of Molecular Biosciences
Karl Franzens Universität Graz
Heinrichstraße 31
8010 Graz

e-Mail: rudolf.zechner@uni-graz.at
phone: +43 316 380 1900
fax: +43 316 380 9056
web: http://imb.uni-graz.at

The Enzyme Network Mediating Lipolysis and Lipid Synthesis in Adipose and Non-adipose Tissues

Obesity, insulin resistance, type-2 diabetes, and atherosclerosis are extremely prevalent metabolic diseases of global dimension. Particularly the metabolism of lipids is crucially involved in the pathogenesis of these diseases. R. Zechner focuses on the biochemistry and cell biology of pathways that control lipid synthesis and lipid catabolism (lipolysis) in adipose and non-adipose tissues. Over the last decade the laboratory concentrated its efforts on the elucidation of the role of lipases in lipid- and energy homeostasis.
Since the start of the DK Molecular Enzymology in 2004, the R. Zechner laboratory discovered a previously unknown triacylglycerol (TG) hydrolase (adipose triglyceride lipase, ATGL) and it’s co-activator (CGI-58). The extensive characterization of mutant mouse models and human patients with ATGL and CGI-58 deficiency demonstrated that these proteins are essential for functional lipolysis. More recent discoveries showed that in addition to its role in energy homeostasis, lipolysis is also crucial for cellular signaling processes and the regulation of gene transcription. In collaboration with the G. Höfler laboratory from DK-Metabolic and Cardiovascular Disease, the R. Zechner group was able to establish a causal role of lipolysis in the pathogenesis of cancer-associated cachexia.

The laboratory currently addresses three main goals:
• Elucidating the detailed mechanistic understanding of the lipolytic process. Lipolysis is heavily regulated by post-translational modifications of lipases and their interaction with regulatory factors. We aim to identify these modifications and co-regulators and determine their physiological role in the lipolytic process.

• Defining the role of lipolysis in lipid-mediated signal transduction. The mechanisms and physiological function of lipolysis in many non-adipose tissues is incompletely understood. Currently we focus on the lipolytic process and its physiological consequences in cardiac muscle, brown adipose tissue and the skin epidermis.

• The role of lipolysis in cancer and cancer-associated cachexia. The realization of the crucial importance of metabolic adaptations in tumorigenesis and tumor growth ignited a new interest in cancer metabolism. Our recent findings support a crucial role of lipolysis in tumor proliferation and the development of cancer-associated cachexia. This topic will represent a major research focus of the R. Zechner laboratory in the coming years.

Laboratory know-how and infrastructure

The IMB provides a state of the art laboratory for the study of all aspects of lipid metabolism with a special emphasis on lipolytic enzymes. Model systems include yeast and mice. Studies in humans are also performed. Special expertise is available for biochemical lipid, lipoprotein and protein analyses, gene cloning, protein expression (in bacteria, yeast, insect and mammalian cell lines), tissue and cell culture techniques, generation of transgenic mice, and the production of conventional and conditional gene knock-outs in mice. Specialized analytical methodology is provided by our facility for mass spectrometry focusing on lipid and protein analysis. The animal facility supports sophisticated analyses of metabolic parameters in mutant mouse models.

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