” It was possible to observe that visceral adipocytes are more prone to infection by SARS-CoV-2. Viral load increased far more in this fat cell type than in subcutaneous adipocytes. The difference in vulnerability compared to subcutaneous adipocytes was observed just in action to the ancestral virus.
” We concluded that the Manaus variation is less effective at contaminating visceral fat cells than the ancestral stress,” Mori said. In other words, the Manaus strain made adipocytes produce more proteins that promote an antiviral response.”
” It was possible to observe that visceral adipocytes are more vulnerable to infection by SARS-CoV-2. Viral load increased far more in this fat cell type than in subcutaneous adipocytes.
Furthermore, the researchers discovered that when visceral adipocytes were contaminated, they produced a larger amount of pro-inflammatory cytokines, which notify the immune system to the presence of a risk to be combated.
An article on the research study was released just recently in the scientific journal Nature Communications. Numerous research groups at UNICAMP collaborated with the group at USP, alongside associates at the Brazilian Bioscience National Laboratory (LNBio-CNPEM), National Cancer Institute (INCA) and DOr Research and Education Institute (IDOR). The principal detectives were Luiz O. Leiria (USP), Mariana Osako (USP) and Daniel Martins-de-Souza (UNICAMP). The research study was funded by FAPESP through 20 jobs (17/08264 -8, 20/05040 -4, 20/04746 -0, 19/00098 -7, 19/05155 -9, 20/04583 -4, 20/15959 -5, 19/26119 -0, 16/00194 -8, 20/04558 -0, 20/04579 -7, 21/10373 -5, 20/08716 -9, 13/07607 -8, 20/04919 -2, 17/01184 -9, 17/23920 -9, 16/24163 -4, 19/04726 -2 and 18/21635 -8).
Viral reservoir
Moris group at UNICAMP was the very first on the planet to reveal– in July 2020– that SARS-CoV-2 can contaminate human fat cells and to suggest that adipose tissue serves as a reservoir for the virus.
” After that, other studies validated that adipocytes can certainly be infected, and when we examined samples from patients who passed away of COVID-19, we found the presence of the virus in adipose tissue to be reasonably frequent, representing about 50% of cases,” Mori stated.
The group then chose to examine whether there were distinctions between the way subcutaneous and visceral adipose cells reacted to infection. As far as metabolic diseases are worried, the evidence in the clinical literature shows visceral fat to be the primary villain, while subcutaneous fat tends to be neutral or perhaps beneficial.
” We wished to see if there was a comparable association in the context of COVID-19,” Mori said. “And in reality, our design recommends that the more visceral fat there is in overweight individuals, the more the infection can duplicate, and this enhances the inflammatory process.”
In subcutaneous adipocytes, on the other hand, the group observed a decline in lipolysis, the breakdown of fats and other lipids by hydrolysis to release fats, which can be utilized as a source of energy throughout physical activity or fasting durations.
” Our hypothesis is that this represents an antiviral cellular action,” Mori said. “There are studies showing that inhibition of lipolysis lowers the replicative capability of SARS-CoV-2, which can be described by the fact that the virus requires lipids to produce its envelope, as well as energy from cells to make copies of its genetic product.” Decreased lipolysis in subcutaneous fat, for that reason, might be positive for the client and problem for the virus.
Contrasting reactions
Visceral adipocytes were exposed to various pressures of SARS-CoV-2: the ancestral family tree initially from Wuhan, China, and isolated from among the first Brazilians diagnosed with COVID-19; and the gamma version (P. 1.), which emerged in late 2020 in Manaus, the capital of Amazonas state in Brazil. The difference in vulnerability compared to subcutaneous adipocytes was observed only in response to the ancestral virus.
” We concluded that the Manaus variation is less effective at infecting visceral fat cells than the ancestral pressure,” Mori stated. “A proteomic analysis [of all the proteins produced by the cells] showed that the Wuhan strain led to a reduction in a number of proteins connected with the cellular reaction to interferon [an immune system mechanism to fight infections], whereas the gamma variation resulted in an increase. To put it simply, the Manaus strain made adipocytes produce more proteins that promote an antiviral response.”
Recent research points to a drop in the variety of serious cases of COVID-19 due to unique variants amongst individuals with weight problems. “But this could be influenced by other aspects, such as vaccination or prior infection. Or these individuals might have been taking extra care because they knew they belonged to a high-risk group,” Mori discussed.
To try to deepen their understanding of all these procedures, the group plans additional experiments including adipocytes cultured with the delta and omicron versions.
Another prepare for future research study is to investigate possible medium- to long-lasting metabolic impacts of infection by SARS-CoV-2. “We wish to discover out whether infection changes the danger of establishing diabetes or heart disease, for example,” Mori stated. “One way of doing so might be to evaluate samples from patients who had COVID-19 and were later submitted to bariatric surgery, in order to see if functional and morphological changes took place in visceral fat as an outcome of the infection.”
Referral: “SARS-CoV-2 contaminates adipose tissue in a fat depot- and viral lineage-dependent way” by Tatiana Dandolini Saccon, Felippe Mousovich-Neto, Raissa Guimarães Ludwig, Victor Corasolla Carregari, Ana Beatriz dos Anjos Souza, Amanda Stephane Cruz dos Passos, Matheus Cavalheiro Martini, Priscilla Paschoal Barbosa, Gabriela Fabiano de Souza, Stéfanie Primon Muraro, Julia Forato, Mariene Ribeiro Amorim, Rafael Elias Marques, Flavio Protasio Veras, Ester Barreto, Tiago Tomazini Gonçalves, Isadora Marques Paiva, Narayana P. B. Fazolini, Carolina Mie Kawagosi Onodera, Ronaldo Bragança Martins Junior, Paulo Henrique Cavalcanti de Araújo, Sabrina Setembre Batah, Rosa Maria Mendes Viana, Danilo Machado de Melo, Alexandre Todorovic Fabro, Eurico Arruda, Fernando Queiroz Cunha, Thiago Mattar Cunha, Marco Antônio M. Pretti, Bradley Joseph 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 Manoel M. Moraes-Vieira, Joyce Maria Annichino Bizzacchi, Tambet Teesalu, Felipe David Mendonça Chaim, Everton Cazzo, Elinton Adami Chaim, José Luiz Proença-Módena, Daniel Martins-de-Souza, Mariana Kiomy Osako, Luiz Osório Leiria and Marcelo A. Mori, 29 September 2022, Nature Communications.DOI: 10.1038/ s41467-022-33218-8.
Cultured distinguished adipocytes: lipids are stained red; the protein ACE-2, which works as the receptor for SARS-CoV-2, is green; cell nuclei are blue. Credit: Amanda Passos & & Flávio Protasio Veras
Two kinds of adipocytes (fat cells) were contaminated in the lab: one obtained from human stem cells separated from subcutaneous tissue and the other separated from stem cells drawn from visceral fat.
Experiments show that visceral fat– fat around the liver, intestines, and other organs, considered a threat factor for heart disease, diabetes, and high blood pressure– contributes more to extreme COVID-19 than subcutaneous fat (under the skin, as in “love deals with”). The experiments were conducted in Brazil by researchers at the State University of Campinas (UNICAMP) and the University of São Paulo (USP).
In order to arrive at this conclusion, Marcelo Mori, a professor at the Institute of Biology at UNICAMP and one of the studys leaders, infected in the laboratory two different kinds of fat cells: one gotten from human stem cells separated from subcutaneous tissue and the other differentiated from stem cells drawn from visceral fatty tissue.