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A2407 - Impact of Methionine/Choline Deficient Diet and Cigarette Smoke Exposure on Pulmonary Homeostasis
Author Block: E. Jubinville1, M. Lafrance1, J. Routhier1, A. Lechasseur2, M. Beaulieu1, M. Paré1, S. Aubin1, M. C. Morissette1; 1Quebec Heart and Lung Institute, Quebec, QC, Canada, 2Medecine, Quebec Heart and Lung Institute, Quebec, QC, Canada.
Introduction: Cigarette smoke exposure has been shown to alter pulmonary lipid transport in humans and mice (Jubinville et al. ERJ 2017; PMID 28889112). Reverse lipid transport is largely initiated in the liver with the genesis of lipoproteins. Altered liver functions may therefore put additional pressure on the lungs, especially during cigarette smoke (CS) exposure. Methionine/choline deficient (MCD) diet is a well-known model used to cause hepatic steatosis in mice. Hypothesis: Damaging the liver reduces reverse lipid transport capacity and exacerbates the pulmonary response to CS. Objectives: To investigate the impact of MCD diet on the pulmonary response to CS. Methods: C57BL/6 mice were fed control or MCD diet and were exposed to room-air or mainstream CS for two or four weeks (2h/day; 5 days/week). Lung and blood cell counts and differentials were performed. ApoA1 levels, serum cholesterol efflux capacity, and serum and bronchoalveolar lavage fluid (BALF) phosphatidylcholine (PC) levels were measured. Lung histology and pulmonary functions (FlexiVent) were also assessed in both protocols. Results: MCD diet significantly reduces total lung and blood cell counts in CS-exposed mice compared to CS-exposed mice fed control diet. BAL neutrophil counts were also reduced in CS-exposed mice fed a MCD diet while the blood pool remained unchanged compared to CS-exposed mice fed a control diet. Serum cholesterol efflux capacity and ApoA1 levels of CS-exposed mice fed a MCD diet were reduced compared to CS controls. Serum PC levels were reduced in CS-exposed mice fed a MCD diet while they remained unchanged in the BALF compared to CS controls. Lung function assessment showed a restrictive pattern in both room-air and CS-exposed MCD-fed mice compared to mice fed control diet. However, we could not observe any fibrosis at lung histology. Conclusion: Our study shows for the first time a negative impact of MCD diet on the lungs and on the pulmonary response to cigarette smoke. Separately investigating these deficiencies will enlighten our understanding, especially since steady supply of choline is required for PC synthesis, the main phospholipid found in pulmonary surfactant.