Medizinische Universität Graz - Research portal
Navigation/Search
- Researchers
- Institutions
- Projects
- Publications
- Partners
- Sponsors
- Equipment
- Knowhow
- Fields of Research
"Faces" of the day:
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Kanti, MM; Striessnig-Bina, I; Wieser, BI; Schauer, S; Leitinger, G; Eichmann, TO; Schweiger, M; Winkler, M; Winter, E; Lana, A; Kufferath, I; Marsh, LM; Kwapiszewska, G; Zechner, R; Hoefler, G; Vesely, PW.
Adipose triglyceride lipase-mediated lipid catabolism is essential for bronchiolar regeneration.
JCI Insight. 2022; 7(9):
Doi: 10.1172/jci.insight.149438
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Leading authors Med Uni Graz
- Höfler Gerald
- Kanti Manu Manjunath
- Vesely Paul
- Co-authors Med Uni Graz
- Eichmann Thomas
- Kufferath Iris
- Kwapiszewska-Marsh Grazyna
- Leitinger Gerd
- Marsh Leigh
- Schauer Silvia
- Strießnig-Bina Isabelle
- Winter Elke
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- The lung airways are constantly exposed to inhaled toxic substances, resulting in cellular damage that is repaired by local expansion of resident bronchiolar epithelial club cells. Disturbed bronchiolar epithelial damage repair lies at the core of many prevalent lung diseases, including chronic obstructive pulmonary disease, asthma, pulmonary fibrosis, and lung cancer. However, it is still not known how bronchiolar club cell energy metabolism contributes to this process. Here, we show that adipose triglyceride lipase (ATGL), the rate-limiting enzyme for intracellular lipolysis, is critical for normal club cell function in mice. Deletion of the gene encoding ATGL, Pnpla2 (also known as Atgl), induced substantial triglyceride accumulation, decreased mitochondrial numbers, and decreased mitochondrial respiration in club cells. This defect manifested as bronchiolar epithelial thickening and increased airway resistance under baseline conditions. After naphthalene‑induced epithelial denudation, a regenerative defect was apparent. Mechanistically, dysfunctional PPARα lipid-signaling underlies this phenotype because (a) ATGL was needed for PPARα lipid-signaling in regenerating bronchioles and (b) administration of the specific PPARα agonist WY14643 restored normal bronchiolar club cell ultrastructure and regenerative potential. Our data emphasize the importance of the cellular energy metabolism for lung epithelial regeneration and highlight the significance of ATGL-mediated lipid catabolism for lung health.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Bronchioles - administration & dosage
- Lipase - genetics, metabolism
- Lipolysis - physiology
- Mice - administration & dosage
- PPAR alpha - metabolism
- Regeneration - administration & dosage
- Triglycerides - metabolism