Obesity and metabolic dysfunction drive sex-associated differential disease profiles in hACE2-mice challenged with SARS-CoV-2.
iScience
; 25(10): 105038, 2022 Oct 21.
Article
em En
| MEDLINE
| ID: mdl-36068847
ABSTRACT
Severe outcomes from SARS-CoV-2 infection are highly associated with preexisting comorbid conditions like hypertension, diabetes, and obesity. We utilized the diet-induced obesity (DIO) model of metabolic dysfunction in K18-hACE2 transgenic mice to model obesity as a COVID-19 comorbidity. Female DIO, but not male DIO mice challenged with SARS-CoV-2 were observed to have shortened time to morbidity compared to controls. Increased susceptibility to SARS-CoV-2 in female DIO was associated with increased viral RNA burden and interferon production compared to males. Transcriptomic analysis of the lungs from all mouse cohorts revealed sex- and DIO-associated differential gene expression profiles. Male DIO mice after challenge had decreased expression of antibody-related genes compared to controls, suggesting antibody producing cell localization in the lung. Collectively, this study establishes a preclinical comorbidity model of COVID-19 in mice where we observed sex- and diet-specific responses that begin explaining the effects of obesity and metabolic disease on COVID-19 pathology.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Risk_factors_studies
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article