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Insulin resistance mediates high-fat diet-induced pulmonary fibrosis and airway hyperresponsiveness through the TGF-β1 pathway

Authors
 Yoon Hee Park  ;  Eun Yi Oh  ;  Heejae Han  ;  Misuk Yang  ;  Hye Jung Park  ;  Kyung Hee Park  ;  Jae-Hyun Lee  ;  Jung-Won Park 
Citation
 EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.51(5) : 59, 2019 
Journal Title
 EXPERIMENTAL AND MOLECULAR MEDICINE 
ISSN
 1226-3613 
Issue Date
2019
Abstract
Prior studies have reported the presence of lung fibrosis and enhanced airway hyperresponsiveness (AHR) in mice with high-fat-diet (HFD)-induced obesity. This study evaluated the role of TGF-β1 in HFD-induced AHR and lung fibrosis in a murine model. We generated HFD-induced obesity mice and performed glucose and insulin tolerance tests. HFD mice with or without ovalbumin sensitization and challenge were also treated with an anti-TGF-β1 neutralizing antibody. AHR to methacholine, inflammatory cells in the bronchoalveolar lavage fluid (BALF), and histological features were evaluated. Insulin was intranasally administered to normal diet (ND) mice, and in vitro insulin stimulation of BEAS-2b cells was performed. HFD-induced obesity mice had increased insulin resistance, enhanced AHR, peribronchial and perivascular fibrosis, and increased numbers of macrophages in the BALF. However, they did not have meaningful eosinophilic or neutrophilic inflammation in the lungs compared with ND mice. The HFD enhanced TGF-β1 expression in the bronchial epithelium, but we found no differences in the expression of interleukin (IL)-4 or IL-5 in lung homogenates. Administration of the anti-TGF-β1 antibody attenuated HFD-induced AHR and lung fibrosis. It also attenuated goblet cell hyperplasia, but did not affect the AHR and inflammatory cell infiltration induced by OVA challenge. The intranasal administration of insulin enhanced TGF-β1 expression in the bronchial epithelium and lung fibrosis. Stimulating BEAS-2b cells with insulin also increased TGF-β1 production by 24 h. We concluded that HFD-induced obesity-associated insulin resistance enhances TGF-β1 expression in the bronchial epithelium, which may play an important role in the development of lung fibrosis and AHR in obesity.
Files in This Item:
T201904258.pdf Download
DOI
10.1038/s12276-019-0258-7
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Park, Kyung Hee(박경희) ORCID logo https://orcid.org/0000-0003-3605-5364
Park, Jung Won(박중원) ORCID logo https://orcid.org/0000-0003-0249-8749
Park, Hye Jung(박혜정) ORCID logo https://orcid.org/0000-0002-1862-1003
Lee, Jae Hyun(이재현) ORCID logo https://orcid.org/0000-0002-0760-0071
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/173182
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