Ahmed I Marwan1, Uladzimir Shabeka2, Julie A Reisz3, Connie Zheng3, Natalie J Serkova4, Evgenia Dobrinskikh5. 1. Division of Pediatric Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado, USArony.marwan@childrenscolorado.org. 2. Division of Pediatric Surgery, Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado, USA. 3. Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, USA. 4. Department of Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado, USA. 5. Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
Abstract
INTRODUCTION: Fetal tracheal occlusion (TO) is currently an experimental approach to drive accelerated lung growth. It is stimulated by mechanotransduction that results in increased cellular proliferation and growth. However, it is currently unknown how TO affects the metabolic landscape of fetal lungs. MATERIALS AND METHODS: TO or sham was performed on fetal rabbits at 26 days followed by lung harvest on day 30. Mass spectrometry was performed to evaluate global metabolic changes. Fluorescence lifetime intensity microscopy (FLIM) was performed to estimate local free/bound NADH relative ratio as an indicator of aerobic glycolysis versus oxidative phosphorylation (glycolysis/OXPHOS). RESULTS: TO results in a metabolic shift from tricarboxylic acid cycle towards glycolysis. FLIM reveals uniform structures in control lungs characterized by similar ratios of free/bound NADH indicating a homogenous topological pattern. Similar uniform structures are observed in shams with some variability in the glycolysis/OXPHOS ratio. In contrast, lungs following TO demonstrate different types of unique distinct topological zones: one with enlarged alveoli and a shift towards glycolysis; the other maintains balance between glycolysis/OXPHOS similar to control lungs. CONCLUSION: We demonstrate for the first time a unique variable topological pattern of metabolism in fetal lungs following TO with a wide variation of metabolism between zones.
INTRODUCTION:Fetal tracheal occlusion (TO) is currently an experimental approach to drive accelerated lung growth. It is stimulated by mechanotransduction that results in increased cellular proliferation and growth. However, it is currently unknown how TO affects the metabolic landscape of fetal lungs. MATERIALS AND METHODS:TO or sham was performed on fetal rabbits at 26 days followed by lung harvest on day 30. Mass spectrometry was performed to evaluate global metabolic changes. Fluorescence lifetime intensity microscopy (FLIM) was performed to estimate local free/bound NADH relative ratio as an indicator of aerobic glycolysis versus oxidative phosphorylation (glycolysis/OXPHOS). RESULTS:TO results in a metabolic shift from tricarboxylic acid cycle towards glycolysis. FLIM reveals uniform structures in control lungs characterized by similar ratios of free/bound NADH indicating a homogenous topological pattern. Similar uniform structures are observed in shams with some variability in the glycolysis/OXPHOS ratio. In contrast, lungs following TO demonstrate different types of unique distinct topological zones: one with enlarged alveoli and a shift towards glycolysis; the other maintains balance between glycolysis/OXPHOS similar to control lungs. CONCLUSION: We demonstrate for the first time a unique variable topological pattern of metabolism in fetal lungs following TO with a wide variation of metabolism between zones.
Authors: Kimberley D Bruce; Evgenia Dobrinskikh; Hong Wang; Ivan Rudenko; Hong Gao; Andrew E Libby; Sachi Gorkhali; Tian Yu; Andrea Zsombok; Robert H Eckel Journal: Metabolites Date: 2020-09-28
Authors: Maria Del Mar Romero-Lopez; Marc Oria; Miki Watanabe-Chailland; Maria Florencia Varela; Lindsey Romick-Rosendale; Jose L Peiro Journal: Metabolites Date: 2021-03-18