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Empagliflozin and Dulaglutide are Effective against Obesity-induced Airway Hyperresponsiveness and Fibrosis in A Murine Model

Authors
 Hye Jung Park  ;  Heejae Han  ;  Eun-Yi Oh  ;  Sung Ryeol Kim  ;  Kyung Hee Park  ;  Jae-Hyun Lee  ;  Jung-Won Park 
Citation
 SCIENTIFIC REPORTS, Vol.9(1) : 15601, 2019 
Journal Title
 SCIENTIFIC REPORTS 
Issue Date
2019
Abstract
Patients with asthma with obesity experience severe symptoms, are unresponsive to conventional asthma treatment, and lack proper pharmacotherapy. Empagliflozin and dulaglutide, developed for diabetes, reduce weight, decrease insulin resistance, and exert additive effects. We evaluated the efficacy of empagliflozin, dulaglutide, and their combination on obesity-induced airway hyperresponsiveness (AHR) and lung fibrosis using a murine model. We assigned C57BL/6J mice to five groups: control, high-fat diet (HFD), and HFD with empagliflozin, dulaglutide, or both. Mice received a 12-week HFD, empagliflozin (5 days/week, oral gavage), and dulaglutide (once weekly, intraperitoneally). Both drugs significantly attenuated HFD-induced weight increase, abnormal glucose metabolism, and abnormal serum levels of leptin and insulin, and co-treatment was more effective. Both drugs significantly alleviated HFD-induced AHR, increased macrophages in bronchoalveolar lavage fluid (BALF), and co-treatment was more effective on AHR. HFD-induced lung fibrosis was decreased by both drugs alone and combined. HFD induced interleukin (IL)-17, transforming growth factor (TGF)-β1, and IL-1β mRNA and protein expression, which was significantly reduced by empagliflozin, dulaglutide, and their combination. Tumour necrosis factor (TNF)-α and IL-6 showed similar patterns without significant differences. HFD-enhanced T helper (Th) 1 and Th17 cell differentiation was improved by both drugs. Empagliflozin and dulaglutide could be a promising therapy for obesity-induced asthma and showed additive effects in combination.
Files in This Item:
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DOI
10.1038/s41598-019-51648-1
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Sung Ryeol(김성렬) ORCID logo https://orcid.org/0000-0001-7418-0049
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
Han, Heejae(한희재)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/174598
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