Milestone for medical research: New method enables comprehensive identification of omega fatty acids

11. 08. 2025 

Omega-3 fatty acids are known to be an essential part of a healthy diet. As humans cannot produce them, they have to be consumed in sufficient amounts. However, omega-6, -7, -9, and -10 fatty acids also play important roles in the metabolism of fats. These numbers indicate the position of the first double bond in a fatty acid chain. Deviations in the omega position can signal enzyme malfunctions or pathological metabolic processes, such as those occurring in cancer. Now, researchers at the University of Graz and the University of California, San Diego present in Nature Communications a novel, effective method to determine omega positions of lipids – the scientific term for fats - in complex biological samples including human tissues and blood. For omega-3 lipids, the first double bond is located at the third carbon atom from the end of the fatty acid chain, hence the number in the name. "Many enzymes in our bodies can utilize only fatty acids with specific double bond positions. Aberrant metabolic processes, such as those occurring in cancer, cardiovascular diseases, or autoimmune disorders, frequently entail alterations in omega positions of lipids," explains Jürgen Hartler, head of the Computational Pharmacology research group at the University of Graz. Therefore, taking a closer look at this structural feature is highly relevant. “Among the enzymes that act specifically on fatty acids with certain double bond positions, phospholipases stand out for their key role in inflammation. This new method now enables the study of these biological mechanisms in unprecedented detail.” adds Edward Dennis, Professor of Chemistry, Biochemistry, and Pharmacology at the University of California, San Diego.

New Computer-Based Method

Until now, the identification of omega positions of intact lipids has been challenging in complex biological samples. Only a few research groups worldwide had access to the required specialized analytical tools such as Evelyn Rampler’s group at the University of Vienna. Hartler, Dennis and their teams, in collaboration with Rampler, are now introducing a new computational method. “Our database in concert with the developed software LC=CL makes omega positions of lipids available in routine chromatography-coupled mass spectrometry methods,” Leonida Lamp, first author of the publication, summarizes this innovation. In this way, researchers worldwide will get access to this crucial information, which will significantly advance lipid research. Lamp adds: “Moreover, our method has proven to be far more sensitive than prior approaches, making omega position information accessible even for lipids in very low concentrations”. Gosia Murawska, co-first author of the publication, gives an example: “A key enzyme among the phospholipases is cPLA2. It has been studied for decades. Now, LC=CL enabled us to prove that cPLA2 specifically converts mead acid, an omega-9 fatty acid. This demonstrates that our method is an essential milestone to advance precise therapeutic strategies, such as for inflammation-related diseases.”

Evelyn Rampler, cooperation partner at the Institute of Analytical Chemistry at the University of Vienna, works on the development and application of novel, high-resolution mass spectrometry and LC-MS workflows. She explains: “Through the targeted use of high-resolution mass spectrometry in combination with innovative EAD fragmentation, we were able to independently confirm the double-bond positions determined by LC=CL—a crucial step in validating the reliability and accuracy of this new method. Our work has thus provided experimental proof that LC=CL works in practice.”

Original publication:

Leonida M. Lamp, Gosia M. Murawska, Joseph P. Argus, Aaron M. Armando, Radu A. Talmazan, Marlene Pühringer, Evelyn Rampler, Oswald Quehenberger, Edward A. Dennis, Jürgen Hartler (2025) Computationally unmasking each fatty acyl C=C position in complex lipids by routine LC-MS/MS lipidomics . In Nature Communications

DOI 10.1038/s41467-025-61911-x

 Scientific Contact University of Vienna

 Scientific Contact

DI Dr.techn. Jürgen Hartler

Assistant Professor of Computational Pharmacology
University of Graz
Institute of Pharmaceutical Sciences
Phone: +43 316 380 5382 Universität Graz
Email: juergen.hartler@uni-graz.at

Dr. Edward A. Dennis

Distinguished Professor of Chemistry, Biochemistry and Pharmacology
University of California, San Diego
Phone: +1 858 336 8241
Email: edennis@ucsd.edu