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A3837 - Effect of High Fat Diet and Aging on Lung Epithelial Stem Cells
Author Block: A. E. Hegab1, M. Ozaki1, S. Kagawa1, T. Betsuyaku2; 1Keio University, Tokyo, Japan, 2Department of Medicine, Keio University, Tokyo, Japan.
Rationale: Lung function is known to decrease with aging, and obese people have lower lung function parameters. In mice, high fat diet (HFD) decreased lifespan independent of body weight, and in humans, it increased the risk of lung cancer. HFD enhanced stemness but also increased tumorigenicity of intestinal stem cells. Aging is believed to reduce number and impair function of stem cells. The purpose of this study is to identify the effect of HFD on both proximal and distal lung stem cells and its interaction with aging. Methods: Both young and aged adult mice were fed HFD chow with 60% higher calorie than the regular control diet for 8 weeks. Body weight was monitored weekly. All mice were examined for changes in their trachea and lung histology, signs of inflammation, with quantification of basal and alveolar stem cells. Mitochondrial number and function will be examined in lung epithelial cells. Both tracheal basal and lung stem cells collected from both young and old control and HFD-fed mice will be cultured in our standardized Colony Forming Assay (CFA, Hegab, Stem Cell Res 2015), to identify changes in their colony forming efficiency (CFE) and differentiation ability. Results: Both young and old mice exposed to HFD gained weight significantly higher than mice fed on regular diet. Histological assessment revealed no change in basal cells but showed a significant increase in number of alveolar type II (AT-II) cells in both young and old mice fed HFD. Aging on its own reduced the number of basal and AT-II cells. Lung histological examination also revealed that aging caused a significant increase in bronchus and vascular-associated lymphoid tissues (BALT, VALT). HFD significantly induced lung inflammation (BALT/VALT) in young mice and further increased the aging-induced lung inflammation. Examination of mitochondria from both proximal and distal lung epithelial cells of the HFD-exposed young and old mice revealed no significant changes in number or function of mitochondria compared to mice on control diet.Ex-vivo organoid culture of cells collected from HFD-exposed mice showed higher CFE in the CFA compared to their controls. Conclusion: HFD induces several histological, inflammatory and functional changes in the lung, and exacerbates the aging-induced lung inflammation.