Exogenous leptin enhances markers of airway fibrosis in a mouse model of chronic allergic airways disease.

Journal Article (Journal Article)

BACKGROUND: Asthma patients with comorbid obesity exhibit increased disease severity, in part, due to airway remodeling, which is also observed in mouse models of asthma and obesity. A mediator of remodeling that is increased in obesity is leptin. We hypothesized that in a mouse model of allergic airways disease, mice receiving exogenous leptin would display increased airway inflammation and fibrosis. METHODS: Five-week-old male and female C57BL/6J mice were challenged with intranasal house dust mite (HDM) allergen or saline 5 days per week for 6 weeks (n = 6-9 per sex, per group). Following each HDM exposure, mice received subcutaneous recombinant human leptin or saline. At 48 h after the final HDM challenge, lung mechanics were evaluated and the mice were sacrificed. Bronchoalveolar lavage was performed and differential cell counts were determined. Lung tissue was stained with Masson's trichrome, periodic acid-Schiff, and hematoxylin and eosin stains. Mouse lung fibroblasts were cultured, and whole lung mRNA was isolated. RESULTS: Leptin did not affect mouse body weight, but HDM+leptin increased baseline blood glucose. In mixed-sex groups, leptin increased mouse lung fibroblast invasiveness and increased lung Col1a1 mRNA expression. Total lung resistance and tissue damping were increased with HDM+leptin treatment, but not leptin or HDM alone. Female mice exhibited enhanced airway responsiveness to methacholine with HDM+leptin treatment, while leptin alone decreased total respiratory system resistance in male mice. CONCLUSIONS: In HDM-induced allergic airways disease, administration of exogenous leptin to mice enhanced lung resistance and increased markers of fibrosis, with differing effects between males and females.

Full Text

Duke Authors

Cited Authors

  • Ihrie, MD; McQuade, VL; Womble, JT; Hegde, A; McCravy, MS; Lacuesta, CVG; Tighe, RM; Que, LG; Walker, JKL; Ingram, JL

Published Date

  • May 24, 2022

Published In

Volume / Issue

  • 23 / 1

Start / End Page

  • 131 -

PubMed ID

  • 35610699

Pubmed Central ID

  • PMC9131622

Electronic International Standard Serial Number (EISSN)

  • 1465-993X

Digital Object Identifier (DOI)

  • 10.1186/s12931-022-02048-z

Language

  • eng

Conference Location

  • England