Impact of Sarcopenic Obesity on Pulmonary Responses to Hyperoxia
Mccravy, MS; Kim, H; Porter, K; Gasier, H; Ingram, JL
Published in: American Journal of Respiratory and Critical Care Medicine
Background: Sarcopenic obesity (SO) is the coexistence of reduced muscle mass and function that occurs in aging and excess body fat. SO is linked to a higher incidence of lung disease than obesity alone, leading to the hypothesis that SO would exacerbate lung injury post-hyperoxic exposure, a model of acute respiratory distress syndrome. Methods: Lean and obese phenotypes were studied in young (6-week) and aged (72-week) C57BL/6J male mice by consuming diets containing 10 or 60% fat for 4 months. Sarcopenia was confirmed by measuring muscle wet weights and grip strength using a small rodent dynamometer. Mice were further divided into exposure group, remaining in room air or 100% oxygen for 48 hours. After exposure, measurements included body and muscle wet weights and grip strength. To evaluate pulmonary physiology, a Flexivent rodent ventilator was used to measure pulmonary compliance (Crs), resistance (Rrs), and elastance (Ers). Following physiology assessment, bronchoalveolar lavage (BAL) fluid was collected, and BAL fluid protein content as well as tissue gene expression of occludin (Ocln), (Tjp1), and claudin 4 (Cldn4) and protein levels of microtubule-associated protein 1A/1B light chain 3 (LC3) were determined. Mortality incidence was recorded. Results: Both groups of mice on 60% fat diet demonstrated significant weight gain relative to age-matched controls (p<0.05). Sarcopenia, indicated by a reduced hind limb force, developed in aged mice regardless of diet. No mortality was observed in the aged groups, though 2 deaths occurred in the lean young group and 5 in the obese young group following hyperoxia exposure. Pulmonary Crs was significantly reduced in both young phenotypes and in the aged lean mice following hyperoxia exposure (Fig). Unexpectedly, no change was observed in compliance following hyperoxia exposure in the aged, obese group. These findings were mirrored in Rrs and Ers, which were increased in all groups following hyperoxia exposure except for the aged obese group. Hyperoxia exposure elevated alveolar protein levels across all groups; however, the increase was less pronounced in the aged obese group compared to both aged lean and young obese groups, suggesting reduced alveolar leak and preservation of alveolar integrity (Fig). No consistent differences were observed in tight junction gene expression among groups. Both aged groups showed increased LC3-II levels following hyperoxia, while the aged obese group also exhibited an increase in LC3-I. Conclusions: Contrary to our hypothesis, obesity in sarcopenia conferred protection against hyperoxic lung injury as opposed to increased severity in young mice.
