Upregulation of inflammatory genes and pathways links obesity to severe COVID-19.

Autor:	Currey J; Tulane National Primate Research Center, Covington, LA 70433, USA; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA., Ellsworth C; Tulane National Primate Research Center, Covington, LA 70433, USA; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA., Khatun MS; Departments of Medicine and Pediatrics, Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, LA 70112, USA; Department of Pulmonary Critical Care and Environmental Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA., Wang C; Tulane National Primate Research Center, Covington, LA 70433, USA; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA., Chen Z; Tulane National Primate Research Center, Covington, LA 70433, USA; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA., Liu S; Tulane National Primate Research Center, Covington, LA 70433, USA; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA., Midkiff C; Tulane National Primate Research Center, Covington, LA 70433, USA., Xiao M; Tulane National Primate Research Center, Covington, LA 70433, USA; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA., Ren M; Tulane National Primate Research Center, Covington, LA 70433, USA; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA., Liu F; Tulane National Primate Research Center, Covington, LA 70433, USA; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA., Elgazzaz M; Southeast Louisiana VA Medical Center, New Orleans, LA 70119, USA., Fox S; Southeast Louisiana VA Medical Center, New Orleans, LA 70119, USA., Maness NJ; Tulane National Primate Research Center, Covington, LA 70433, USA; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA., Rappaport J; Tulane National Primate Research Center, Covington, LA 70433, USA; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA., Lazartigues E; Southeast Louisiana VA Medical Center, New Orleans, LA 70119, USA., Blair R; Tulane National Primate Research Center, Covington, LA 70433, USA., Kolls JK; Departments of Medicine and Pediatrics, Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, LA 70112, USA; Department of Pulmonary Critical Care and Environmental Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA., Mauvais-Jarvis F; Department of Medicine, Section of Endocrinology and Metabolism, Tulane University School of Medicine, New Orleans, LA 70112, USA; Southeast Louisiana VA Medical Center, New Orleans, LA 70119, USA., Qin X; Tulane National Primate Research Center, Covington, LA 70433, USA; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA. Electronic address: xqin2@tulane.edu.
Jazyk:	angličtina
Zdroj:	Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2024 Oct; Vol. 1870 (7), pp. 167322. Date of Electronic Publication: 2024 Jun 26.
DOI:	10.1016/j.bbadis.2024.167322
Abstrakt:	Obesity is a risk factor for developing severe COVID-19. However, the mechanism underlying obesity-accelerated COVID-19 remains unclear. Here, we report results from a study in which 2-3-month-old K18-hACE2 (K18) mice were fed a western high-fat diet (WD) or normal chow (NC) over 3 months before intranasal infection with a sublethal dose of SARS-CoV2 WA1 (a strain ancestral to the Wuhan variant). After infection, the WD-fed K18 mice lost significantly more body weight and had more severe lung inflammation than normal chow (NC)-fed mice. Bulk RNA-seq analysis of lungs and adipose tissue revealed a diverse landscape of various immune cells, inflammatory markers, and pathways upregulated in the infected WD-fed K18 mice when compared with the infected NC-fed control mice. The transcript levels of IL-6, an important marker of COVID-19 disease severity, were upregulated in the lung at 6-9 days post-infection in the WD-fed mice when compared to NC-fed mice. Transcriptome analysis of the lung and adipose tissue obtained from deceased COVID-19 patients found that the obese patients had an increase in the expression of genes and the activation of pathways associated with inflammation as compared to normal-weight patients (n = 2). The K18 mouse model and human COVID-19 patient data support a link between inflammation and an obesity-accelerated COVID-19 disease phenotype. These results also indicate that obesity-accelerated severe COVID-19 caused by SARS-CoV-2 WA1 infection in the K18 mouse model would be a suitable model for dissecting the cellular and molecular mechanisms underlying pathogenesis. Competing Interests: Declaration of competing interest The authors declare no conflicts of interest. (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Full Text from ScienceDirect