MALDI-imaging: a tool to study lipid distribution in liver tissue during regeneration

Liver is the central organ of intermediary metabolism. Upon intoxication of mice with CCl₄ pericentral hepatocytes die due to the generation of reactive oxygen species. A rapid regeneration process starts. Already 2d after intoxication the concentration of lipids within the viable part of remaining liver tissue increased, as can be shown by Oil Red O staining. It has been suggested (Michalopoulos 2009) that these lipids are used as fuel and building blocks for the regeneration of new hepatic cells. After 7 days regeneration is complete, enzymatic activities of the pericentral hepatocytes (e.g. glutamine synthetase) are restored and the lipid concentration has returned to normal levels (determined by Oil Red O staining).

Different time-points during liver regeneration were analyzed using MALDI-imaging (Astigarraga et al. 2008) in order to detect the spacial distribution of lipids in hepatic lobules. An area of 3.5×2.5mm with a resolution of 50µm was scanned and the lipid composition of each area in the range of m/z=400 to 1000 Da was recorded. Phospholipids and acylglycerols were detected on the tissue slices. Two days after CCl₄ intoxication lipid composition was changed compared to normal liver. Even though total lipid concentration had normalized within 7 days the period during which the enzymatic activity of glutamine synthetase was already restored, the lipid composition did not yet fully return to normal level. Furthermore, the MALDI images clearly showed that the lipids are heterogeneously distributed within the undisturbed as well as in the intoxicated liver tissue.

equal contribution of AV and SZ

Literatur: Astigarraga E et al. (2008) Anal. Chem. 80, 9105-9114 Michalopoulos GM (2007) J. Cell Physiol. 213, 286-300

MALDI - lipid - regeneration