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

Hye Jung Park, Heejae Han, Eun Yi Oh, Sung Ryeol Kim, Kyung Hee Park, Jae Hyun Lee, Jung Won Park

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number15601
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

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High Fat Diet
Fibrosis
Obesity
Asthma
Pharmaceutical Preparations
Th17 Cells
Weights and Measures
Lung
Th1 Cells
Morbid Obesity
Interleukin-17
empagliflozin
dulaglutide
Bronchoalveolar Lavage Fluid
Transforming Growth Factors
Therapeutics
Leptin
Interleukin-1
Inbred C57BL Mouse
Insulin Resistance

All Science Journal Classification (ASJC) codes

  • General

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Park, Hye Jung ; Han, Heejae ; Oh, Eun Yi ; Kim, Sung Ryeol ; Park, Kyung Hee ; Lee, Jae Hyun ; Park, Jung Won. / Empagliflozin and Dulaglutide are Effective against Obesity-induced Airway Hyperresponsiveness and Fibrosis in A Murine Model. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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Empagliflozin and Dulaglutide are Effective against Obesity-induced Airway Hyperresponsiveness and Fibrosis in A Murine Model. / Park, Hye Jung; Han, Heejae; Oh, Eun Yi; Kim, Sung Ryeol; Park, Kyung Hee; Lee, Jae Hyun; Park, Jung Won.

In: Scientific reports, Vol. 9, No. 1, 15601, 01.12.2019.

Research output: Contribution to journalArticle

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