Lipidomics and metabolomics signatures of SARS-CoV-2 mediators/receptors in peripheral leukocytes, jejunum and colon

Other authors

[Mayneris-Perxachs J] Departament de Diabetis, Endocrinologia i Nutrició, Hospital Universitari Dr. Josep Trueta, Girona, Spain. Grup d'Eumetabolisme i Salut, Institut d’Investigació Biomèdica de Girona (IDIBGI), Salt, Spain. Centre d'Investigació Biomèdica en Xarxa de Fisiopatologia de l'Obesitat i la Nutrició (CIBEROBN), Madrid, Spain. Institut d'Investigació Biomèdica de Girona (IDIBGI), Salt, Spain. [Moreno-Navarrete JM] Departament de Diabetis, Endocrinologia i Nutrició, Hospital Universitari Dr. Josep Trueta, Girona, Spain. Grup d'Eumetabolisme i Salut, Institut d’Investigació Biomèdica de Girona (IDIBGI), Salt, Spain. Centre d'Investigació Biomèdica en Xarxa de Fisiopatologia de l'Obesitat i la Nutrició (CIBEROBN), Madrid, Spain. Departament de Ciències Mèdiques, Facultat de Medicina, Universitat de Girona, Girona, Spain. Institut d'Investigació Biomèdica de Girona (IDIBGI), Salt, Spain. [Ballanti M] Departament de Medicina de Sistemes, Universitat de Roma Tor Vergata, Roma, Italy. Centre d'Aterosclerosi, Policlinico Tor Vergata, Roma, Italy. [Monteleone G, Paoluzi OA] Departament de Medicina de Sistemes, Universitat de Roma Tor Vergata, Roma, Italy. [Mingrone G] Departament de Medicina Interna, Universitat Catòlica, Roma, Italy. Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Itàlia. Diabetes and Nutritional Sciences, Hodgkin Building, Guy's Campus, King's College London, London, United Kingdom. [Garre J] Departament de Ciències Mèdiques, Facultat de Medicina, Universitat de Girona, Girona, Spain. Institut d’Investigació Biomèdica de Girona (IDIBGI), Salt, Spain. Grup de Recerca en Envelliment, Discapacitat i Salut, Institut d’Investigació Biomèdica de Girona (IDIBGI), Salt, Spain. Departament d’Infermeria, Universitat de Girona, Girona, Spain. [Puig J] Departament de Radiologia (IDI), Hospital Universitari de Girona Doctor Josep Trueta, Institut Català de la Salut (ICS), Girona, Spain. [Fernández-Real JM] Departament de Diabetis, Endocrinologia i Nutrició, Hospital Universitari de Girona Doctor Josep Trueta, Institut Català de la Salut (ICS), Girona, Spain

Institut d'Assistència Sanitària

Publication date

2021-11-23T07:57:24Z

2021-11-23T07:57:24Z

2021-11-08



Abstract

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Lipidómicas; Metabolómicas; Receptores virales


Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Lipidòmiques; Metabolòmiques; Receptors virals


Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Lipidomics; Metabolomics; Viral receptors


Cell surface receptor-mediated viral entry plays a critical role in this infection. Well-established SARS-CoV-2 receptors such as ACE2 and TMPRSS2 are highly expressed in the gastrointestinal tract. In fact, there are evidences that SARS-CoV-2 infects epithelial cells from the digestive system. However, emerging research has identified novel mediators such as DPP9, TYK2, and CCR2, all playing a critical role in inflammation. We evaluated the expression of SARS-CoV-2 receptors in peripheral leukocytes (n=469), jejunum (n=30), and colon (n=37) of three independent cohorts by real-time PCR, RNA-sequencing, and microarray transcriptomics. We also performed HPCL-MS/MS lipidomics and metabolomics analyses to identify signatures linked to SARS-CoV-2 receptors. We found markedly higher peripheral leukocytes ACE2 expression levels in women compared to men, whereas the intestinal expression of TMPRSS2 was positively associated with BMI. Consistent lipidomics signatures associated with the expression of these mediators were found in both tissues and peripheral leukocytes involving n-3 long-chain PUFAs and arachidonic acid-derived eicosanoids, which play a key role in the regulation of inflammation and may interfere with viral entry and replication. Medium- and long-chain hydroxy acids, which have shown to interfere in viral replication, were also liked to SARS-CoV2 receptors. Gonadal steroids were also associated with the expression of some of these receptors, even after controlling for sex. The expression of SARS-CoV2 receptors was associated with several metabolic and nutritional traits in different cell types. This information may be useful in the design of potential therapies targeted at coronavirus entry.

Document Type

Article

Language

English

Publisher

Elsevier

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Computational and Structural Biotechnology Journal;19

https://dx.doi.org/10.1016%2Fj.csbj.2021.11.007

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Attribution-NonCommercial-NoDerivatives 4.0 International

http://creativecommons.org/licenses/by-nc-nd/4.0/

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