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SARS-CoV-2 infects adipose tissue in a fat depot- and viral lineage-dependent manner

2022; Nature Portfolio; Volume: 13; Issue: 1 Linguagem: Inglês

10.1038/s41467-022-33218-8

2041-1723

Tatiana D. Saccon, Felippe Mousovich‐Neto, Raissa G. Ludwig, Victor Corasolla Carregari, Ana Beatriz dos Anjos Souza, Amanda Stephane Cruz dos Passos, Matheus Cavalheiro Martini, Priscilla P. Barbosa, Gabriela Fabiano de Souza, Stéfanie Primon Muraro, Julia Forato, Mariene R. Amorim, Rafael Elias Marques, Flávio P. Veras, Ester A. Barreto, Tiago Tomazini Gonçalves, Isadora Marques Paiva, Narayana P. B. Fazolini, Carolina Mie Kawagosi Onodera, Ronaldo B. Martins, Paulo Henrique Cavalcanti de Araújo, Sabrina Setembre Batah, Rosa Maria Mendes Viana, Danilo Machado de Melo, Alexandre Todorovic Fabro, Eurico Arruda, Fernando Q. Cunha, Thiago M. Cunha, Marco Antônio M. Pretti, Bradley J. Smith, Henrique Marques‐Souza, Thiago L. Knittel, Gabriel Palermo Ruiz, Gerson S. Profeta, Tereza Cristina Minto Fontes-Cal, Mariana Boroni, Marco Aurélio Ramirez Vinolo, Alessandro S. Farias, Pedro M. Moraes‐Vieira, Joyce Maria Annichino Bizzacchi, Tambet Teesalu, Felipe David Mendonça Chaim, Everton Cazzo, Élinton Adami Chaim, José Luiz Proença‐Módena, Daniel Martins‐de‐Souza, Mariana Kiomy Osako, Luiz O. Leiria, Marcelo A. Mori,

Adipokines, Inflammation, and Metabolic Diseases

Abstract Visceral adiposity is a risk factor for severe COVID-19, and a link between adipose tissue infection and disease progression has been proposed. Here we demonstrate that SARS-CoV-2 infects human adipose tissue and undergoes productive infection in fat cells. However, susceptibility to infection and the cellular response depends on the anatomical origin of the cells and the viral lineage. Visceral fat cells express more ACE2 and are more susceptible to SARS-CoV-2 infection than their subcutaneous counterparts. SARS-CoV-2 infection leads to inhibition of lipolysis in subcutaneous fat cells, while in visceral fat cells, it results in higher expression of pro-inflammatory cytokines. Viral load and cellular response are attenuated when visceral fat cells are infected with the SARS-CoV-2 gamma variant. A similar degree of cell death occurs 4-days after SARS-CoV-2 infection, regardless of the cell origin or viral lineage. Hence, SARS-CoV-2 infects human fat cells, replicating and altering cell function and viability in a depot- and viral lineage-dependent fashion.