PT  - JOURNAL ARTICLE
AU  - Selle, Jaco
AU  - Dinger, Katharina
AU  - Kesler, Hanan
AU  - Georgomanolis, Theodoros
AU  - Vohlen, Christina
AU  - Wilke, Rebecca
AU  - Dötsch, Jörg
AU  - Alejandre Alcazar, Miguel A.
TI  - Maternal and perinatal obesity arrests alveolarization and reduces alveolar progenitor cells in offspring
AID  - 10.1183/13993003.congress-2020.5241
DP  - 2020 Sep 07
TA  - European Respiratory Journal
PG  - 5241
VI  - 56
IP  - suppl 64
4099  - http://erj.ersjournals.com/content/56/suppl_64/5241.short
4100  - http://erj.ersjournals.com/content/56/suppl_64/5241.full
SO  - Eur Respir J2020 Sep 07; 56
AB  - Background: Obesity contributes to lung diseases and regeneration. Prior studies from our group showed that perinatal and maternal obesity induces bronchial and vascular remodeling in later life. However, the impact of obesity on alveolarization and the alveolar regenerative niche remains uncertain.Aims: (1) To investigate the impact of maternal and perinatal obesity on alveolar formation and on alveolar epithelial type II cells (ATII) as alveolar progenitor cells; (2) To study the effect of white adipose tissue (WAT) and its adipocytokines on ATII.Methods: 1) Female mice were fed with high-fat diet (HFD) or standard-diet (SD) prior mating, and during pregnancy and lactation. The offspring’s lungs were analyzed at postnatal day 21 (P21). (2) Murine lung epithelial cells (MLE12) were exposed to WAT conditioned medium (CMWAT), Interleukin 6 (IL-6) or Leptin.Results: (1) Lung RNAseq transcriptomic profiling at P21 followed by KEGG pathway analysis identified in the HFD-group pathways involved in cell survival and lung development. Quantitative histomorphometry demonstrated an increased alveolar surface and a reduced radial alveolar count (RAC) in the HFD when compared to the SD-group, indicating reduced alveolarization. Immunofluorescence staining for surfactant protein C, an ATII marker, showed reduction of ATII by 52 %, suggesting that perinatal obesity depletes alveolar regenerative capacity. (2) Exposure of MLE12 to CMWAT IL‑6, or Leptin induced cellular senescence and reduced cell survival.Conclusion: We identified a novel adipose tissue-lung axis linking perinatal overactive adipose tissue secretome to depletion of alveolar progenitor cells and reduced alveolar formation.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 5241.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).