Research Grants 23/05773-0 - Virologia, Adipócitos - BV FAPESP
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SARS-CoV-2 interactions with adipocytes and metabolic implications

Abstract

During the COVID-19 outbreak by the SARS-CoV-2 virus, a high prevalence of severe acute respiratory syndrome was observed in overweight and obese patients, who also had a higher hospitalization rate, including admission to intensive care units. Several studies report that adipose tissue is a reservoir of several pathogens, including viruses, and we recently published the presence of the virus (protein and genome) in the adipose tissue of patients who died of COVID-19. We identified that adipocytes from the visceral deposit express higher levels of the ACE2 protein, are more permissive to SARS-CoV-2, and have a higher expression of pro-inflammatory cytokines after infection than those from the subcutaneous deposit. Recent studies indicate that COVID-19 affects adipose tissue metabolism, either by impairing the insulin response or by inducing brown adipose tissue activation and beige adipocyte differentiation. Thus, the studies have evaluated the metabolic effect of COVID-19, but the contribution of SARS-CoV-2 infection on the adipocyte remains obscure. Given this context and the observation of published and preliminary results from our group, we hypothesize is that the adipocyte is a replication site for SARS-CoV-2 positively influenced by the volume of lipid droplets. Furthermore, SARS-CoV-2 infection facilitates the differentiation of beige adipocytes in the visceral depot of white adipose tissue, but reduces this potential in the subcutaneous depot. In this project, we will evaluate the susceptibility and permissiveness of adipocytes to SARS-CoV2 infection, replication kinetics, and subcellular localization of SARS-CoV-2 in adipocytes. We will also assess the functionality of lipolysis and lipophagy in infected adipocytes; and its ability to alter fatty acid storage and differentiate into beige adipocytes. We will investigate whether the chronic and low-grade inflammation found in the adipose tissue of obese patients contributes to the increase in infectivity and viral replication in adipocytes by quantification of the pro-inflammatory cytokine´s impact on SARS-CoV-2 replication in preadipocytes and adipocytes. Finally, we will evaluate the persistence of SARS-CoV-2 in infected adipocytes for 30 days, as well as the presence of the virus in adipose tissue samples from a hamster model under a hypercaloric or normocaloric diet. Studies aimed at deepening the knowledge of these SARS-CoV-2 and adipose tissue relationships are of great relevance to understanding the viral pathogenesis to allow for more appropriate clinical management of the disease in obese patients, as well as to evaluate possible long-term impacts of patients who have had COVID-19. (AU)

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VEICULO: TITULO (DATA)
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