Fatty Liver:
Graz Researchers Publish Preliminary Stage of New Diagnosis Method

Fatty liver isn't always what it appears to be. A team of researchers from the University of Graz, the Medical University of Graz and Graz University of Technology has shown for the first time that the specific composition of the fat droplets in the liver cells can point to the different causes of the illness. This knowledge is a foundation stone for the development of new therapeutic methods. The research findings were published in the renowned Journal of Lipid Research and even made front page.

Fatty foods, fasting or genetic loading: a fatty liver can occur due to various metabolic disorders. For instance, "non-alcoholic fatty liver" is acquired through eating excessive fatty foods in combination with insulin resistance. A genetically conditioned blockade of the fat-splitting enzyme ATGL can be another cause. Also, fasting can lead to increased fatty deposits in the liver since lipids – fats – make their way to the liver from other parts of the body. The composition of the lipid droplets in the liver cells can give information about the underlying metabolic disorder of a fatty liver, as researchers from Graz have discovered in the context of a EU-funded project.

Characteristic fat pattern

"It has been shown that the composition of the lipid droplets varies", reports Univ.-Prof. Dr. Friedrich Spener of the Institute of Molecular Biosciences at the University of Graz. "Depending on the cause of the illness, there are a variety of lipid molecules of different quantities in the droplets. This results in a characteristic pattern which reveals whether the fatty liver is a consequence of various forms of nutritional stress or genetic stress. The triglyceride profile is especially suitable by which make this distinction", the biochemist and molecular biologist summarises.

Research in Graz trio

The three Graz universities which combine their research at the interface between man, medicine and technology under the moniker "BioTechMed-Graz" also joined forces in this project and shared the work. The team surrounding Friedrich Spener isolated lipid droplets from liver epithelial cells which were then examined by Dr. Harald Köfeler and his staff at the Center for Medical Research (ZMF) at the Medical University of Graz using mass spectrometry (MS). Dr. Gerhard Thallinger and his team at the Institute for Genomics and Bioinformatics at Graz University of Technology evaluated the results using bioinformatic methods they developed themselves. The methodological innovation lies, on the one hand, in the application of a special MS platform which provides high quantities of data in high-throughput mode, and, on the other hand, in the bioinformatic evaluation process which allows the individual lipid molecules and their overall pattern to be automatically identified. This "lipidomic approach" is the method of choice since, according to estimates, there are over 100,000 different lipid molecules. "Regarding this method of the automatic quantification of lipid molecules – a patent has been applied for. In the long-term it is an approach which can also be used in clinical diagnostics", explains bioinformatics scientist Gerhard Thallinger.

Graz as centre of European fat research

Along with Cambridge, Dresden, Lyon and Regensburg, Graz is one of the big centres of lipidomics research in Europe. On the initiative of Friedrich Spener and Univ.-Prof. Dr. Sepp D. Kohlwein, the different working groups have been merged under one virtual roof at the Lipidomics Research Center Graz. The research is part of the inter-university platform BioTechMed-Graz.

Publication: Chitraju, C., Trötzmüller M., Hartler J., Wolinski H., Thallinger G., Haemmerle G., Zechner R., Zimmermann R., Köfeler H., Spener F.: The impact of genetic stress by ATGL deficiency on the lipidome of lipid droplets from murine hepatocytes. Journal of Lipid Research. 2013, Vol. 54, Number 8, 2185-2194.