Diagnostik & Forschungszentrum für Molekulare BioMedizin

Tumormetabolismus

Research focus

Lung neoplasia when ATGL is absent

Upper left, normal lung morphology is seen in an H&E section from a 9 months old control mouse lung. Bronchioles are indicated by “Br”. ATGL knockout mice, where the fatal cardiac phenotype has been rescued by ATGL re-expression in the heart (Atgl-KO/cTg) develop lung neoplastic lesions when aged for 8 months and more. Upper right and lower left, a bronchiolar intraepithelial pre-neoplastic lesion (PNL), and an invasive lesion are present, respectively. Bottom right, a CK-19 IHC stained section from a 21 months old Atgl-KO/cTg lung shows a normal Br above-, and an invasive adenocarcinoma (AC) below- the dotted line.

Altered bronchiolar club cell ultrastructure

TEM images show typical stretches of bronchiolar epithelia. Atgl-KO/cTg bronchiolar epithelial club cells show fewer mitochondria (20-30 electron dense discs per club-cell cross section) as compared to the controls (40-60 per club-cell cross section). Moreover, several round, medium electron dense, lipid droplets (5-10/cellular cross section) appear in club cells from Atgl-KO/cTg mice. Lipid droplets are absent in controls.

Future plan

Impaired regeneration when ATGL is absent

Publications (2018-2019)
  • Kolleritsch, S; Kien, B; Schoiswohl, G; Diwoky, C; Schreiber, R; Heier, C; Maresch, LK; Schweiger, M; Eichmann, TO; Stryeck, S; Krenn, P; Tomin, T; Kolb, D; Rülicke, T; Hoefler, G; Wolinski, H; Madl, T; Birner-Gruenberger, R; Haemmerle, G, 2019
    Low cardiac lipolysis reduces mitochondrial fission and prevents lipotoxic heart dysfunction in Perilipin 5 mutant mice.
    Cardiovasc Res. 2019;
  • Leopold, C; Duta-Mare, M; Sachdev, V; Goeritzer, M; Maresch, LK; Kolb, D; Reicher, H; Wagner, B; Stojakovic, T; Ruelicke, T; Haemmerle, G; Hoefler, G; Sattler, W; Kratky, D, 2019
    Hepatocyte-specific lysosomal acid lipase deficiency protects mice from diet-induced obesity but promotes hepatic inflammation.
    Biochim Biophys Acta Mol Cell Biol Lipids. 2019; 1864(4):500-511
  • Maresch, LK; Benedikt, P; Feiler, U; Eder, S; Zierler, KA; Taschler, U; Kolleritsch, S; Eichmann, TO; Schoiswohl, G; Leopold, C; Wieser, BI; Lackner, C; Rülicke, T; van Klinken, J; Kratky, D; Moustafa, T; Hoefler, G; Haemmerle, G, 2019
    Intestine-Specific Overexpression of Carboxylesterase 2c Protects Mice From Diet-Induced Liver Steatosis and Obesity.
    Hepatol Commun. 2019; 3(2):227-245
  • Pajed, L; Wagner, C; Taschler, U; Schreiber, R; Kolleritsch, S; Fawzy, N; Pototschnig, I; Schoiswohl, G; Pusch, LM; Wieser, BI; Vesely, P; Hoefler, G; Eichmann, TO; Zimmermann, R; Lass, A, 2019 Hepatocyte-specific deletion of lysosomal acid lipase leads to cholesteryl ester but not triglyceride or retinyl ester accumulation.
    J Biol Chem. 2019; 294(23):9118-9133
  • Al-Zoughbi, W; Schauer, S; Pichler, M; Hoefler, G, 2018
    Early Loss of Forkhead Transcription Factor, O Subgroup, Member 1 Protein in the Development of Pancreatic Ductal Adenocarcinoma.
    Pathobiology. 2018; 85(5-6): 342-347.
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