High fat feeding protects mice from ventilator-induced lung injury, via neutrophil-independent mechanisms
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Objective:
Obesity has a complex impact on acute respiratory distress syndrome patients, being associated with increased likelihood of developing the syndrome but reduced likelihood of dying. We propose that such observations are potentially explained by a model in which obesity influences the iatrogenic injury that occurs subsequent to intensive care admission. This study therefore investigated whether fat feeding protected mice from ventilator-induced lung injury.
Design:
In vivo study.
Setting:
University research laboratory.
Subjects:
Wild-type C57Bl/6 mice or tumor necrosis factor receptor 2 knockout mice, either fed a high-fat diet for 12–14 weeks, or age-matched lean controls.
Interventions:
Anesthetized mice were ventilated with injurious high tidal volume ventilation for periods up to 180 minutes.
Measurements and Main Results:
Fat-fed mice showed clear attenuation of ventilator-induced lung injury in terms of respiratory mechanics, blood gases, and pulmonary edema. Leukocyte recruitment and activation within the lungs were not significantly attenuated nor were a host of circulating or intra-alveolar inflammatory cytokines. However, intra-alveolar matrix metalloproteinase activity and levels of the matrix metalloproteinase cleavage product soluble receptor for advanced glycation end products were significantly attenuated in fat-fed mice. This was associated with reduced stretch-induced CD147 expression on lung epithelial cells.
Conclusions:
Consumption of a high-fat diet protects mice from ventilator-induced lung injury in a manner independent of neutrophil recruitment, which we postulate instead arises through blunted up-regulation of CD147 expression and subsequent activation of intra-alveolar matrix metalloproteinases. These findings may open avenues for therapeutic manipulation in acute respiratory distress syndrome and could have implications for understanding the pathogenesis of lung disease in obese patients.
Obesity has a complex impact on acute respiratory distress syndrome patients, being associated with increased likelihood of developing the syndrome but reduced likelihood of dying. We propose that such observations are potentially explained by a model in which obesity influences the iatrogenic injury that occurs subsequent to intensive care admission. This study therefore investigated whether fat feeding protected mice from ventilator-induced lung injury.
Design:
In vivo study.
Setting:
University research laboratory.
Subjects:
Wild-type C57Bl/6 mice or tumor necrosis factor receptor 2 knockout mice, either fed a high-fat diet for 12–14 weeks, or age-matched lean controls.
Interventions:
Anesthetized mice were ventilated with injurious high tidal volume ventilation for periods up to 180 minutes.
Measurements and Main Results:
Fat-fed mice showed clear attenuation of ventilator-induced lung injury in terms of respiratory mechanics, blood gases, and pulmonary edema. Leukocyte recruitment and activation within the lungs were not significantly attenuated nor were a host of circulating or intra-alveolar inflammatory cytokines. However, intra-alveolar matrix metalloproteinase activity and levels of the matrix metalloproteinase cleavage product soluble receptor for advanced glycation end products were significantly attenuated in fat-fed mice. This was associated with reduced stretch-induced CD147 expression on lung epithelial cells.
Conclusions:
Consumption of a high-fat diet protects mice from ventilator-induced lung injury in a manner independent of neutrophil recruitment, which we postulate instead arises through blunted up-regulation of CD147 expression and subsequent activation of intra-alveolar matrix metalloproteinases. These findings may open avenues for therapeutic manipulation in acute respiratory distress syndrome and could have implications for understanding the pathogenesis of lung disease in obese patients.
Date Issued
2017-08-01
Date Acceptance
2017-02-04
Citation
Critical Care Medicine, 2017, 45 (8), pp.e831-e839
ISSN
1530-0293
Publisher
Lippincott, Williams & Wilkins
Start Page
e831
End Page
e839
Journal / Book Title
Critical Care Medicine
Volume
45
Issue
8
Copyright Statement
© by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Sponsor
Wellcome Trust
British Journal of Anaesthesia
Wellcome Trust
Grant Number
092851/Z/10/Z
BJA/RCoA 2010(1) NIAA
Subjects
Science & Technology
Life Sciences & Biomedicine
Critical Care Medicine
General & Internal Medicine
acute respiratory distress syndrome
inflammation
matrix metalloproteinases
mechanical ventilation
obesity
BODY-MASS INDEX
RESPIRATORY-DISTRESS-SYNDROME
VIVO MOUSE MODEL
CHOLECYSTOKININ RECEPTORS
MARGINATED MONOCYTES
TIDAL VOLUMES
HOST-DEFENSE
OBESITY
LEPTIN
ASSOCIATION
Emergency & Critical Care Medicine
1103 Clinical Sciences
1110 Nursing
1117 Public Health And Health Services
Publication Status
Published
Date Publish Online
2017-04-19