Energy and Lipid Metabolism

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Energy and lipid metabolism in mammalian cells

Obesity, diabetes, and cardiovascular diseases are daunting modern-day epidemics. In Western Europe more than 50% of the population is overweight and approximately 15 million people die from cardiovascular diseases such as heart attacks and stroke every year. These conditions are often caused by disorders of fat metabolism, resulting in a massive accumulation of fat in various tissues and of cholesterol in the walls of arteries.

 

Fats are known to perform long-term storage of energy, but they also act as signaling molecules in the body. Consequently, fat is stored not only in adipose tissue, but also in smaller amounts in almost all cells of the body. Special fat cleaving enzymes, called lipases, are used to remobilize stored fat from cellular depots. Normal lipid and energy metabolism requires complex regulation by a network of signaling processes.

 

At the Institute of Molecular Biosciences various research teams focus of different aspects of energy and lipid metabolism. Besides cell culture experiments we are also model organisms. Some of our researchers rely on yeast, a single cell organism, which can be cultivated and genetically modified easily. Other groups rely on mouse models since most metabolic pathways are identical among mammals. We hope that our finding identify new therapeutic targets or help prevent disease.

 

 

Univ.-Prof. Dr. Rudolf ZECHNER

Contact:

Heinrichstrasse 31/2

8010 Graz

Room: 0026-02-0098

email: rudolf.zechner(at)uni-graz.at

 tel: +43-316-380-1900

Fax: 0316/380-9016

Prof. Zechner has dedicated his scientific life to elucidating lipolysis, the enzymatic breakdown of lipids. For each lipolytic step distinct enzymes (lipases) are responsible, a process which is fine-tuned by a large number of molecular factors. This ensures an adequate response to changes in the metabolic state of the body. Zechner and his team have discovered that an enzyme called “Adipose Triglyceride Lipase” (ATGL) is responsible for the initial and rate-limiting step in the degradation of neutral lipids, the main storage form of fats. This finding has changed the lipolytic dogma that hormone-sensitive lipase is responsible for the breakdown of triglycerides. The co-factor CGI-58 increases ATGL activity 20-fold.

Zechner’s current work focusses on the regulation of lipolysis in various tissues as well as on regulatory signals involved in these processes. Moreover, his team tries to elucidate molecular mechanisms that contribute to disease development causally linked to obesity. He also studies the interdepenence of lipolysis and cancer-associated cachexia. Cachexia is the life-threatening wasting of fat and muscle mass often associated with severe disease such as cancer and AIDS and is often the actual cause of death in these patients.

Prof. Zechner has coordinated numerous research networks. Currently, he is the speaker of the SFB LIPOTOX and the European coordinator of the Leducq research network TNT. His scientific achievements have won various national and international awards, including the most prestigious Austrian research price, the Wittgenstein Award, in 2007.

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Assoz. Univ.-Prof. Dr. Robert ZIMMERMANN

Contact:

Heinrichstrasse 31/2

8010 Graz

Room: 0026-03-0004

email: robert.zimmermann(at)uni-graz.at

tel: +43-316-380-1914

We are interested in the biological characterization of enzymes catalyzing the degradation of lipids in mammalian cells. These lipolytic enzymes, designated as lipases, play key roles in many biological and pathological processes because they control the availability of lipids for cellular energy production, synthetic reactions, and signaling events. A large number of genetic diseases have been identified which exhibit deficiencies in phospholipid, triacylglycerol, or cholesterylester catabolism. Moreover, changes in lipolytic activities have been associated with common metabolic disorders, such as obesity, dyslipidemia, and type 2 diabetes. Nevertheless, many lipases are poorly characterized or remain to be discovered. The aim of our research is to identify novel lipases and to explain their function with the help of biochemical, cell biological, and molecular biological methods.

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Assoz. Univ.-Prof. Dr. Günter HÄMMERLE

Contact:

Heinrichstrasse 31/2

8010 Graz

Room: 0026-02-0008

email: guenter.haemmerle(at)uni-graz.at

tel: +43-316-380-1910

My research interests lie in the understanding of the role of lipolytic enzymes and co-factors in energy metabolism in oxidative tissues and the skin. Virtually every cell of the body deposits triacylglycerol (TG) within lipid droplets (LD). The mobilization of adipose tissue TGs and the release of free fatty acids into the blood circulation delivers oxidative substrates to peripheral organs including the heart and liver. Imbalances in this process can be causative for the development of metabolic disorders including obesity, type 2 diabetes, hepatic steatosis and heart disease. The generation and characterization of mice lacking or overexpressing neutral lipid hydrolases and co-factors including hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL) and comparative gene identification-58 (CGI-58) substantially increased our understanding of the role of these enzymes in the development of metabolic disorders. Studying the function of lipolytic candidate genes in cell culture experiments delivers novel insights in the role of these proteins in lipid metabolism. Ongoing studies generating and characterizing mice lacking or overexpressing neutral lipid hydrolases and co-factors in a specific organ will increase our understanding of the role of these proteins in the control of energy catabolism and the formation of the skin barrier.

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Assoz. Univ.-Prof. Dr. Achim LASS

Contact:

Heinrichstrasse 31/2

8010 Graz

Room: 0026-03-006

email: achim.lass(at)uni-graz.at

tel: +43 316 380-1926

My research focuses on the identification and characterization of mammalian lipases which are involved in the mobilization of neutral lipids. Neutral lipids are stored in lipid droplets of various cell types. One of them, triacylglycerol, is a fatty acid ester of glycerol and functions as major energy source during nutrial scarcity. Fatty acid esters of retinol, so called retinyl esters, represent an inert storage form of vitamin A which is known to be essential for growth and development. Two major lipid stores are important for either the deposition of triacylglycerol or retinyl esters. In the adipose tissue large quantities of triacylglycerol, generally termed as fat, are stored. In the liver, a specific cell type, the hepatic stellate cells, contain more than 80% of body’s vitamin A reserves in form of retinyl esters. We attempt to identify in proteomic or genetic approaches potential candidate genes for the hydrolysis of neutral lipid esters, in particular triacylglycerol and retinyl esters. The physiological role of these candidate genes are then studied in in vitro activity assays and cell experiments employing overexpression and silencing techniques. For some genes studies are then extended to transgenic or knock-out mouse models.

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Ass.-Prof. Dr. Karina PREISS-LANDL

Contact:

Heinrichstrasse 31/II

8010 Graz

Room: 0026-02-0008

e-mail: karina.landl(at)uni-graz.at

tel: +43-316-380-1910

Our primary focus lies on the identification and characterization of the various components organized in the “lipolysome” catalyzing the coordinated breakdown of triacylglycerol stores in adipose tissue. The “lipolysome” certainly contains lipolytic enzymes like adipose triglyceride lipase (ATGL) or hormone-sensitive lipase (HSL), but also various components potentially working as scaffolding proteins, lipid carrier proteins or proteins modulating the enzymatic activity. Using TAP technology (Tandem Affinity Purification) we aim to screen for these still obscure components. Candidates we have already identified as part of the “lipolysome” are studied using biochemical, genetic, cell biological, and structural biological methods to determine their physiological relevance in lipid metabolism.

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Drosophila Energy and Lipid Metabolism

Univ.-Prof. Dr.rer.nat. Ronald P. Kühnlein

Contact:

Humboldtstraße 50/2.OG

A-8010 Graz

Room: 0045-02-0174

email: ronald.kuehnlein(at)uni-graz.at

Tel.: +43 316 380 5504

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Energy and lipid metabolism in yeast cells

Univ.-Prof. Dr. Sepp D. KOHLWEIN

Contact:

Humboldtstrasse 50/II

8010 Graz

Room: 0045020020

email: sepp.kohlwein(at)uni-graz.at

tel: +43-316-380-5487

Our research interests focus on fatty acid and neutral lipid (triglyceride) metabolism in the yeast Saccharomyces cerevisiae. We are specifically interested in the regulation of fatty acid synthesis and the regulatory and potentially lipotoxic roles of fatty acids in cellular metabolism. These studies involve genetic, biochemical and analytical (mass spectrometry), molecular, and cell biological techniques. Cytological studies in yeast and other cell types and tissues involve video and confocal laser scanning microscopy, and also CARS, SHG and other multi photon applications, to investigate the spatial and dynamic organization of lipid metabolic processes. We use genetically modified yeast model systems to better understand the molecular basis of lipid-associated disorders in humans.

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Ass.-Prof. Dr. Klaus NATTER

Contact:

Humboldstrasse 50/II

8010 Graz

e-mail: klaus.natter(at)uni-graz.at

tel: +43-316-380-1928

 

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Dr. Karin ATHENSTAEDT

Contact:

Humboldtstraße 50/II

8010 Graz

email: karin.athenstaedt@uni-graz.at

tel: +43-316-380-3954

 


In our research we focus on the biosynthesis of phosphatidic acid which plays a central role in lipid metabolism. Phosphatidic acid is an important intermediate not only in biosynthetic pathways yielding glycerophospholipids (membrane lipids), but also in triacylglycerol (storage lipid) synthesis. We investigate regulatory aspects of phosphatidic acid biosynthesis as well as the impact of defects in these regulatory processes on lipid (cell) metabolism. For these studies we use as our experimental system the budding yeast Saccharomyces cerevisiae, an invaluable model organism to determine the principles of lipid metabolic processes. In our studies we apply molecular biological, cell biological and biochemical methods.
 

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Dr. Oksana Tehlivets

Contact

Humboldtstrasse 50/II

8010 Graz

email: oksana.tehlivets(at)uni-graz.at

tel: +43-316-380-5500; 5504

Our research interests focus on the elucidation of the pathological mechanisms triggered by deficient methylation. The key enzyme of methylation metabolism, S-adenosyl-L-homocysteine hydrolase, is an exceptionally well-conserved enzyme exhibiting more than 70 % identity between human and yeast orthologs. Deficiency of this enzyme in humans leads to severe pathological consequences and is associated with the accumulation of the strong product inhibitor of S-adenosyl-L-methionine (AdoMet)-dependent methyltransferases, S-adenosyl-L-homocysteine (AdoHcy). Also a common pathological condition, hyperhomocysteinemia, exhibits the accumulation of AdoHcy that has been proven to be an even more sensitive marker than homocysteine for homocysteine-associated disorders.

Phospholipid methylation consumes the major amount of AdoMet both in yeast as well as in mammals. Its inhibition results in the accumulation of neutral lipids, but can also interfere with the membrane function, since phosphatidylcholine synthesized via phospholipid methylation displays higher levels of unsaturated fatty acids. In order to understand this and other mechanisms induced by AdoHcy accumulation we use, under application of biochemical, genetic and molecular biological methods, yeast as an experimental model.

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Sectretary lipid metabolism in mammalian cells
Heinrichstrasse 31/IIA-8010 Graz

Martina Halbedl
+43 (0)316 380 - 1900
+43 (0)316 380 - 9016

Open for visitors:
Mo-Fr: 09:00-12:00 Uhr

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Secretary lipid metabolism in mammalian cells
Heinrichstrasse 31/IIA-8010 Graz

Birgit Konrad
+43 (0)316 380 - 1922
+43 (0)316 380 - 9016

Open for visitors:
Mo-Fr: 09:00-12:00 Uhr

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Secretary lipid metabolism in Drosophila and yeast cells
Humboldtstrasse 50/IIA-8010 Graz

E. Tatjana Mozga
+43 (0)316 380 - 5485
+43 (0)316 380 - 9854

Open for visitors:
Di-Fr: 09:00-12:00

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