Gert van der Hoek
In Memoriam - Editor, Senior Moderator
Crit Care Med. Author manuscript; available in PMC 2018 Feb 1.
Published in final edited form as:
Crit Care Med. 2017 Aug; 45(8): e831–e839.
doi: 10.1097/CCM.0000000000002403
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 (VILI).
Design
In vivo study.
Setting
University research laboratory.
Subjects
Wildtype C57Bl/6 mice or TNF 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 VILI 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 (MMP) activity and levels of the MMP cleavage product sRAGE 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 VILI in a manner independent of neutrophil recruitment, which we postulate instead arises through blunted upregulation of CD147 expression and subsequent activation of intra-alveolar MMPs. These findings may open avenues for therapeutic manipulation in ARDS, and could have implications for understanding the pathogenesis of lung disease in obese patients.
Published in final edited form as:
Crit Care Med. 2017 Aug; 45(8): e831–e839.
doi: 10.1097/CCM.0000000000002403
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 (VILI).
Design
In vivo study.
Setting
University research laboratory.
Subjects
Wildtype C57Bl/6 mice or TNF 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 VILI 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 (MMP) activity and levels of the MMP cleavage product sRAGE 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 VILI in a manner independent of neutrophil recruitment, which we postulate instead arises through blunted upregulation of CD147 expression and subsequent activation of intra-alveolar MMPs. These findings may open avenues for therapeutic manipulation in ARDS, and could have implications for understanding the pathogenesis of lung disease in obese patients.