Impact of Obesity and Ageing on the Expression of Key Mediators of SARS-CoV-2 Infection in Human Adipose Tissue.

Inês Correia-Sá, Alexandra M Gouveia, Delminda Neves, Adelino Leite-Moreira, Inês Falcão-Pires, Adriana R Rodrigues, Mariana Ferreira, Henrique Almeida, Francisca Saraiva, Maria Salazar, Sandra Marisa Oliveira, Carlos Pinho, Mariana Jarnalo

Journal: International journal of molecular sciences 2025;26(15):

PMID: 40806445

Abstract

Increased body mass index (BMI) and age are associated with COVID-19 severity. SARS-CoV-2 infection occurs through ACE2 binding, with TMPRSS2, ADAM17, and NRP1 facilitating this process. This study describes how adipose tissue (AT) location, BMI, age, and obesity affect these proteins' expression. AT was collected from subcutaneous (abdominal superficial [AS], abdominal deep [AD], thigh [T]) and visceral (epiploon [E]) areas from middle-aged women without obesity (BMI 23.9 kg/m, age 48.3 years). Subcutaneous AT was also obtained from middle-aged women with previous obesity (BMI 24.8 kg/m, previously 41.7 kg/m, age 46.9 years), older women with obesity (BMI 32.3 kg/m, age 70.8 years), and older women without obesity (BMI 23.7 kg/m, age 70.6 years). ACE2, TMPRSS2, ADAM17, and NRP1 expression was evaluated by qPCR and Western blotting. All proteins were more expressed in visceral AT. ACE2, TMPRSS2, and NRP1 positively correlated with BMI in AS and/or E, while NRP1 correlated with age in T. In subcutaneous AT, ACE2 and NRP1 were more influenced by obesity while TMPRSS2 was more age-dependent. In women with previous obesity, ACE2 and NRP1 levels decreased, while TMPRSS2 and ADAM17 remained unchanged. These findings highlight the differential influence of visceral AT, obesity, and age on the expression of SARS-CoV-2 cell entry mediators, potentially contributing to COVID-19 severity.

Address: Unidade de Biologia Experimental, Departamento de Biomedicina, Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.; i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto/IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.; Unidade de Biologia Experimental, Departamento de Biomedicina, Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.; Cardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.; Department of Plastic and Reconstructive Surgery, Instituto Português de Oncologia do Porto FG, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.; Department of Plastic and Reconstructive Surgery, Instituto Português de Oncologia do Porto FG, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal.; Department of Plastic, Reconstructive and Aesthetic Surgery, and Burn Unit, Centro Hospitalar e Universitário de São João, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.; Department of Plastic, Reconstructive and Aesthetic Surgery, and Burn Unit, Centro Hospitalar e Universitário de São João, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.; Unidade de Biologia Experimental, Departamento de Biomedicina, Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.; i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto/IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.; Faculty of Nutrition and Food Sciences of the University of Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
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