High Fat Diet Induces Lung Fibrosis in ApoE‐deficient Mice Potentially Through Increase in Systemic and Lung Tumor Necrosis Factor

Abstract

High fat is increasingly considered the basis for not only cardiovascular pathologies but also several complications affecting other organs such as lungs. In this study, we examined the effect of high fat on lung integrity using ApoE−/− mice model of high‐fat (HF) diet‐induced atherosclerosis. A 12 week HF diet regimen induced systemic production of TNF‐α, IFN‐γ, GMC‐SF, RANTES, IL‐1α, IL‐2, and IL‐12 with TNF‐α as the predominant cytokine. Concomitantly, TNF‐α, IFN‐γ, and MIP‐1α were detected in brochoalveolar lavage fluids of these mice, coinciding with lung inflammation. Such airway inflammation was associated with marked collagen deposition in lungs of ApoE−/−mice, and correlated well with an increase in tissue TGF‐β1 levels and MMP‐9 activity. In vitro exposure of mouse lung cells to oxidized‐ LDL induced a time‐dependent expression of TNF‐α. Repeated intra‐tracheal administration of TNF‐α, induced a robust collagen deposition in WT mice similar to that induced by HF diet in ApoE−/− mice. TNF‐α administration induced expression of several factors critical for lung fibrosis, such as TGF‐β1, adhesion molecules, collagen type‐I in the lungs of WT mice. Altogether, these results suggest that HF may promote chronic inflammatory conditions conducive to lung fibrosis potentially through TNF‐α‐mediated processes, clearly demonstrating the influence of cardiovascular inflammation on lung homeostasis.