Long-term high fat diet aggravates the risk of lung fibrosis and lung cancer: transcriptomic analysis in the lung tissues of obese mice.

Abstract

Background: Previous studies reported significant relationships between obesity and pulmonary dysfunction. Here, we investigated genetic alterations in the lung tissues of high fat diet (HFD) induced obese mouse through transcriptomic and molecular analyses.

Methods: Eight-week-old male C57BL/6J mice were fed either a normal chow diet (NCD) or HFD for 12 weeks. We performed RNA sequencing, functional analysis of altered genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway data, Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis, protein network analysis, quantitative real-time polymerase chain reaction, and Western blotting.

Results: We performed RNA sequencing analysis in the lung tissue of HFD mice. GO and KEGG pathway data presented higher expressions of genes related to lung fibrosis, and the changes of several pathways including regulation of nitrogen compound metabolic process, G protein-coupled receptor signaling, cancer pathway, and small cell lung cancer pathway. DAVID analysis and protein network analysis showed the changes of vascular endothelial growth factor, hypoxia-inducible factor-1 and rat sarcoma virus signaling related to vascular permeability, and protein network of MYC proto-oncogene gene related to cancer. In addition, we found increased protein and mRNA levels of the growth/differentiation factor 15 and alpha smooth muscle actin genes related to lung fibrosis in lung tissue of HFD mice.

Conclusions: HFD contributes to an increased risk of lung fibrosis and lung cancer. Thus, we propose that the genetic modulation and the molecular regulation of target pathways are essential to suppress pulmonary fibrosis in obese patients.