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Adipose triglyceride lipase-mediated lipid catabolism is essential for bronchiolar regeneration.

Authors :
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
Source :
JCI insight [JCI Insight] 2022 May 09; Vol. 7 (9). Date of Electronic Publication: 2022 May 09.
Publication Year :
2022

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.

Details

Language :
English
ISSN :
2379-3708
Volume :
7
Issue :
9
Database :
MEDLINE
Journal :
JCI insight
Publication Type :
Academic Journal
Accession number :
35349484
Full Text :
https://doi.org/10.1172/jci.insight.149438