High fat diet induces airway remodeling in ApoE deficient mice: An association with an increase in circulatory and airway inflammatory factors

Abstract

ObjectiveTo examine the effect of high fat (HF) diet and associated hypercholesterolemia on airway integrity in mice.MethodsThe HF diet‐induced hypercholesterolemia and atherogenesis mouse (ApoE−/−) model was used to conduct the study.ResultsHF diet induced systemic production of inflammatory cytokines including TNF‐α, IFN‐γ, GMC‐SF, RANTES, IL‐1α, IL‐2, and IL‐12 in ApoE−/− mice with TNFα as the predominant cytokine. Concomitantly, TNF‐α, IFN‐γ, and MIP‐1α were detected in brochoalveolar lavage fluids of these mice, coinciding with airway inflammation consisting primarily of monocytes/macrophages. Such airway inflammation was associated with marked collagen deposition, an increase in MMP‐9 activity and TGF‐β distribution in lungs of HF‐fed ApoE−/− mice. Direct intratracheal TNFα‐administration induced an inflammation pattern in wild type mice similar to that observed in HF diet‐fed ApoE−/− mice suggesting that TNFα may be an important player in hypercholesterolemia‐induced airway inflammation. Indeed, TNFα administration induced expression of MCP‐1, IL‐1β, TGFα1, adhesion molecules, collagen 1 and TNFα itself in the lungs of treated mice, all of which are known to be important for airway remodeling.ConclusionThese results suggest that a HF diet and associated hypercholesterolemia may promote chronic inflammatory conditions in lungs that are conducive to airway remodeling.