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© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Obese patients with non-alcoholic steatohepatitis (NASH) are prone to severe forms of COVID-19. There is an urgent need for new treatments that lower the severity of COVID-19 in this vulnerable population. To better replicate the human context, we set up a diet-induced model of obesity associated with dyslipidemia and NASH in the golden hamster (known to be a relevant preclinical model of COVID-19). A 20-week, free-choice diet induces obesity, dyslipidemia, and NASH (liver inflammation and fibrosis) in golden hamsters. Obese NASH hamsters have higher blood and pulmonary levels of inflammatory cytokines. In the early stages of a SARS-CoV-2 infection, the lung viral load and inflammation levels were similar in lean hamsters and obese NASH hamsters. However, obese NASH hamsters showed worse recovery (i.e., less resolution of lung inflammation 10 days post-infection (dpi) and lower body weight recovery on dpi 25). Obese NASH hamsters also exhibited higher levels of pulmonary fibrosis on dpi 25. Unlike lean animals, obese NASH hamsters infected with SARS-CoV-2 presented long-lasting dyslipidemia and systemic inflammation. Relative to lean controls, obese NASH hamsters had lower serum levels of angiotensin-converting enzyme 2 activity and higher serum levels of angiotensin II—a component known to favor inflammation and fibrosis. Even though the SARS-CoV-2 infection resulted in early weight loss and incomplete body weight recovery, obese NASH hamsters showed sustained liver steatosis, inflammation, hepatocyte ballooning, and marked liver fibrosis on dpi 25. We conclude that diet-induced obesity and NASH impair disease recovery in SARS-CoV-2-infected hamsters. This model might be of value for characterizing the pathophysiologic mechanisms of COVID-19 and evaluating the efficacy of treatments for the severe forms of COVID-19 observed in obese patients with NASH.

Details

Title
Diet-Induced Obesity and NASH Impair Disease Recovery in SARS-CoV-2-Infected Golden Hamsters
Author
Briand, François 1 ; Sencio, Valentin 2   VIAFID ORCID Logo  ; Robil, Cyril 2   VIAFID ORCID Logo  ; Heumel, Séverine 2 ; Deruyter, Lucie 2 ; Machelart, Arnaud 2   VIAFID ORCID Logo  ; Barthelemy, Johanna 2   VIAFID ORCID Logo  ; Bogard, Gemma 2   VIAFID ORCID Logo  ; Hoffmann, Eik 2   VIAFID ORCID Logo  ; Infanti, Fabrice 3 ; Domenig, Oliver 4 ; Chabrat, Audrey 5   VIAFID ORCID Logo  ; Virgile, Richard 5 ; Prévot, Vincent 6   VIAFID ORCID Logo  ; Nogueiras, Ruben 7   VIAFID ORCID Logo  ; Wolowczuk, Isabelle 2 ; Pinet, Florence 8   VIAFID ORCID Logo  ; Sulpice, Thierry 1 ; Trottein, François 2   VIAFID ORCID Logo 

 Physiogenex SAS, F-31750 Escalquens, France 
 Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 9017-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France 
 PLETHA, Institut Pasteur de Lille, F-59000 Lille, France 
 Attoquant Diagnostics, A-1010 Vienna, Austria 
 Sciempath Labo, F-37270 Larçay, France 
 Univ. Lille, INSERM, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S 1172, European Genomic Institute for Diabetes (EGID), F-59000 Lille, France 
 Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), S-15781 Santiago de Compostela, Spain 
 Univ. Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, F-59000 Lille, France 
First page
2067
Publication year
2022
Publication date
2022
Publisher
MDPI AG
e-ISSN
19994915
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2716619983
Copyright
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.