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

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Lipidomics and metabolomics signatures of SARS-CoV-2 mediators/receptors in peripheral leukocytes, jejunum and colon
Computational and Structural Biotechnology Journal ( IF 4.4 ) Pub Date : 2021-11-08 , DOI: 10.1016/j.csbj.2021.11.007
Jordi Mayneris-Perxachs _{1,

2,

3,

4} , José Maria Moreno-Navarrete _{1,

2,

3,

4,

5} , Marta Ballanti _{6,

7} , Giovanni Monteleone ₆ , Omero Alessandro Paoluzi ₆ , Geltrude Mingrone _{8,

9,

10} , Philippe Lefebvre ₁₁ , Bart Staels ₁₁ , Massimo Federici _{6,

7} , Josep Puig _{4,

5,

12,

13,

14} , Josep Garre _{4,

5,

15,

16} , Rafael Ramos _{4,

5,

17} , José-Manuel Fernández-Real _{1,

2,

3,

4,

5}

Affiliation

Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, Spain.
Eumetabolism and Health Group, Girona Biomedical Research Institute (IdibGi), Girona, Spain.
Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain.
Girona Biomedical Research Institute (IDIBGI), Dr. Josep Trueta University Hospital, Catalonia, Spain.
Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain.
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
Center for Atherosclerosis, Policlinico Tor Vergata, Rome, Italy.
Department of Internal Medicine, Catholic University, Rome, Italy.
Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Diabetes and Nutritional Sciences, Hodgkin Building, Guy's Campus, King's College London, London, United Kingdom.
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, F-59000 Lille, France.
Institute of Diagnostic Imaging (IDI)-Research Unit (IDIR), Parc Sanitari Pere Virgili, Barcelona, Spain.
Medical Imaging, Girona Biomedical Research Institute (IdibGi), Girona, Spain.
Department of Radiology (IDI), Dr. Josep Trueta University Hospital, Girona, Spain.
Research Group on Aging, Disability and Health, Girona Biomedical Research Institute (IdIBGi), Girona, Spain.
Serra-Húnter Professor. Department of Nursing, University of Girona, Girona Spain.
Vascular Health Research Group of Girona (ISV-Girona). Jordi Gol Institute for Primary Care Research (Institut Universitari per a la RecercaenAtencióPrimària Jordi Gol I Gorina -IDIAPJGol), Catalonia, Spain.

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 , , and , 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 expression levels in women compared to men, whereas the intestinal expression of was positively associated with BMI. Consistent lipidomics signatures associated with the expression of these mediators were found in both tissues and peripheral leukocytes involving 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.

中文翻译：

外周白细胞、空肠和结肠中 SARS-CoV-2 介质/受体的脂质组学和代谢组学特征

细胞表面受体介导的病毒进入在这种感染中起着关键作用。 ACE2 和 TMPRSS2 等成熟的 SARS-CoV-2 受体在胃肠道中高度表达。事实上，有证据表明SARS-CoV-2从消化系统感染上皮细胞。然而，新兴研究已经发现了新型介质，例如、、和，它们都在炎症中发挥着关键作用。我们通过实时 PCR、RNA 测序和微阵列评估了三个独立队列的外周白细胞 (n = 469)、空肠 (n = 30) 和结肠 (n = 37) 中 SARS-CoV-2 受体的表达转录组学。我们还进行了 HPCL-MS/MS 脂质组学和代谢组学分析，以确定与 SARS-CoV-2 受体相关的特征。我们发现，与男性相比，女性外周白细胞表达水平明显更高，而肠道表达与 BMI 呈正相关。在涉及长链 PUFA 和花生四烯酸衍生的类二十烷酸的组织和外周白细胞中发现了与这些介质表达相关的一致脂质组学特征，它们在炎症调节中发挥关键作用，并可能干扰病毒进入和复制。中链和长链羟基酸已被证明可以干扰病毒复制，也受到 SARS-CoV2 受体的喜爱。即使在控制性别之后，性腺类固醇也与其中一些受体的表达有关。 SARS-CoV2受体的表达与不同细胞类型的多种代谢和营养特征相关。这些信息可能有助于设计针对冠状病毒进入的潜在疗法。

更新日期：2021-11-08

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