Lipidomics of liver metabolic disorders

We use shotgun lipidomics to better understand the metabolism in liver in normal and pathological conditions and pursue three major research avenues:

  • Lipidome profiles in liver zonation. Histologically liver has a robust architecture, which defines metabolic zonation of this organ. The liver lobule contains periportal and pericentral hepatocytes, which show different metabolic behaviour. This behaviour is determined by the blood flow direction and oxygen gradient. The zonation is typically characterized at the protein and transcriptional levels; however, lipid profiles remain elusive. Additionally, we aim to study gender-dependent differences in the whole lipidome profile and in various liver zones. This work is performed in collaboration with Dr. Madlen Matz-Soja and her working group at the University Hospital in Leipzig (Matz-Soja lab).
  • Non-alcoholic fatty liver disease (NAFLD) – is a liver disease characterized by the lipid accumulation in hepatocytes. We aim to investigate the role of risk markers of NAFLD in liver lipid metabolism by performing liver lipidome profiling of large cohort of patients. This project is a collaborative project with Dr. Jochen Hampe from the University Hospital in Dresden (Hampe lab).
  • Hepatocellular carcinoma (HCC) is a primary liver cancer with malignant hepatocyte neoplasm. We target to study lipid intratumor heterogeneity and its effect on liver zonation. Dr. Oskar Knittelfelder from our lab has developed the method of laser-captured microdissection, which allows not only to perform liver imaging and to distinguish periportal zones from pericentral, but also to perform deep lipidome analysis of various lipid classes and species of various liver zones. Together with Dr. Thorsten Cramer and Merve Erdem from University Hospital in Aachen we aim to obtain the knowledge of lipidome changes in HCC including the changes in liver zonation (Cramer lab).

Original Publication

Veera Raghavan Thangapandi, Oskar Knittelfelder, Mario Brosch, Eleonora Patsenker, Olga Vvedenskaya, Stephan Buch, Sebastian Hinz, Alexander Hendricks, Marina Nati, Alexander Herrmann, Devavrat Ravindra Rekhade, Thomas Berg, Madlen Matz-Soja, Klaus Huse, Edda Klipp, Josch K Pauling, Judith Ah Wodke, Jacobo Miranda Ackerman, Malte von Bonin, Elmar Aigner, Christian Datz, Witigo von Schönfels, Sophie Nehring, Sebastian Zeissig, Christoph Röcken, Andreas Dahl, Trian Chavakis, Felix Stickel, Andrej Shevchenko, Clemens Schafmayer, Jochen Hampe, Pallavi Subramanian
Loss of hepatic Mboat7 leads to liver fibrosis.
Gut, Art. No. doi: 10.1136/gutjnl-2020-320853 (2020)
DOI

Eugenia Marbach-Breitrück, Madlen Matz-Soja, Ute Abraham, Wolfgang Schmidt-Heck, Susanne Sales, Christiane Rennert, Matthias Kern, Susanne Aleithe, Luise Spormann, Carlo Thiel, Raffaele Gerlini, Katrin Arnold, Nora Klöting, Reinhard Guthke, Damjana Rozman, Raffaele Teperino, Andrej Shevchenko, Achim Kramer, Rolf Gebhardt
Tick-tock hedgehog-mutual crosstalk with liver circadian clock promotes liver steatosis.
J Hepatol, 70(6) 1192-1202 (2019)
DOI

Christiane Rennert, Sebastian Vlaic, Eugenia Marbach-Breitrück, Carlo Thiel, Susanne Sales, Andrej Shevchenko, Rolf Gebhardt, Madlen Matz-Soja
The Diurnal Timing of Starvation Differently Impacts Murine Hepatic Gene Expression and Lipid Metabolism - A Systems Biology Analysis Using Self-Organizing Maps.
Front Physiol, 9 Art. No. 1180 (2018)
DOI

Oskar Knittelfelder, Sofia Traikov, Olga Vvedenskaya, Andrea Schuhmann, Sandra Segeletz, Anna Shevchenko, Andrej Shevchenko
Shotgun Lipidomics Combined with Laser Capture Microdissection: A Tool To Analyze Histological Zones in Cryosections of Tissues.
Anal Chem, 90(16) 9868-9878 (2018)
DOI

Jan Böttger, Katrin Arnold, Carlo Thiel, Christiane Rennert, Susanne Aleithe, Ute Hofmann, Sebastian Vlaic, Susanne Sales, Andrej Shevchenko, Madlen Matz-Soja
RNAi in murine hepatocytes: the agony of choice-a study of the influence of lipid-based transfection reagents on hepatocyte metabolism.
Arch Toxicol, 89(9) 1579-1588 (2015)
DOI

Matthias Kern, Joanna Kosacka, Nico Hesselbarth, Julia Brückner, John T Heiker, Gesine Flehmig, Ingrid Klöting, Peter Kovacs, Madlen Matz-Soja, Rolf Gebhardt, Knut Krohn, Susanne Sales, Kerstin Abshagen, Andrej Shevchenko, Michael Stumvoll, Matthias Blüher, Nora Klöting
Liver-restricted repin1 deficiency improves whole-body insulin sensitivity, alters lipid metabolism, and causes secondary changes in adipose tissue in mice.
Diabetes, 63(10) 3295-3309 (2014)
DOI 

Collaborations

Hample labCoskun labKlipp labPauling lab and LiSyM
Matz-Soja lab Cramer lab

Dr. Olga Vvedenskaya

Contact: olga.vvedenskaya(at)mpi-cbg.de