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