COVID-19 News: Brazilian Study Reveals That SARS-CoV-2 Has A Greater Affinity For Visceral Adipocytes That Results In Higher Risk Of Disease Severity
: A new study by researchers from University of Campinas-Brazil (UNICAMP) and Ribeirão Preto Medical School, University of São Paulo-Brazil (USP) has found that the SARS-CoV-2 virus has a greater affinity for visceral adipocytes compared to subcutaneous adipocytes, replicating faster and causing higher viral loads which in turn increases the various inflammatory triggers leading to increased disease severity and increased risk of mortality! The study also found that visceral fat can also be viral reservoirs of the novel coronavirus.
It is already known that visceral adiposity is a risk factor for severe COVID-19, and a link between adipose tissue infection and disease progression has been proposed.
The study team demonstrated 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.
Importantly, 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.
Also, viral load and cellular response are attenuated when visceral fat cells are infected with the SARS-CoV-2 gamma variant.
Interestingly, 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.
The study findings were published in the peer reviewed journal: Nature Communications.
The study findings showed that visceral fat ie fat around the liver, intestines and other organs, considered a risk factor for cardiovascular disease, diabetes and high blood pressure, contributes more to severe COVID-19 than subcutaneous fat (under the skin, as in "love handles").
Dr Marcelo Mori, a professor at UNICAMP's Institute of Biology and one of the leaders of the study, infected in the laboratory two types of adipocytes (fat cells): one obtained from human stem cells isolated from subcutaneous tissue and the other differentiated from stem cells taken from visceral fatty tissue.
Dr Mori told COVID-19 News
reporters, "It was possible to observe that visceral adipocytes are more susceptible to infection by SARS-CoV-2. Viral load increased far more in this fat cell type than in subcutaneous adipocytes. We believe this was due mainly to higher levels of the protein ACE-2, to which the virus binds to invade cells, on the cell surface.”
The study team also found that when visceral adipocytes were infected, they produced a larger amount of pro-inflammatory cytokines, which warn the
immune system of the existence of a threat to be combated.
Numerous other scientists at UNICAMP collaborated with the group at USP, alongside colleagues at the Brazilian Bioscience National Laboratory (LNBio-CNPEM), National Cancer Institute (INCA) and D'Or Research and Education Institute (IDOR). The principal investigators were Dr Luiz O. Leiria (USP), Dr Mariana Osako (USP) and Dr Daniel Martins-de-Souza (UNICAMP).
Dr Mori's team at UNICAMP was the first in the world to show in July 2020 that SARS-CoV-2 can infect human fat cells and to suggest that adipose tissue serves as a reservoir for the virus.
Dr Mori added, "After that, other studies confirmed that adipocytes can indeed be infected, and when we analyzed samples from patients who died of COVID-19, we found the presence of the virus in adipose tissue to be relatively frequent, corresponding to about 50% of cases!”
The study team then decided to investigate whether there were differences between the way visceral and subcutaneous adipose cells responded to infection.
Accordingly, as far as metabolic diseases are concerned, the evidence in the scientific literature shows visceral fat to be the main villain, while subcutaneous fat tends to be neutral or even beneficial.
Dr Mori further added, "We wanted to see if there was a similar association in the context of COVID-19. And in fact our model suggests that the more visceral adipose tissue there is in obese individuals, the more the virus can replicate, and this amplifies the inflammatory process."
However, in subcutaneous adipocytes, the study team observed a decrease in lipolysis, the breakdown of fats and other lipids by hydrolysis to release fatty acids, which can be used as a source of energy during physical activity or fasting periods.
Dr Mori said, "Our hypothesis is that this represents an antiviral cellular response. There are studies showing that inhibition of lipolysis lowers the replicative capacity of SARS-CoV-2, which can be explained by the fact that the virus needs lipids to produce its envelope, as well as energy from cells to make copies of its genetic material. Reduced lipolysis in subcutaneous adipose tissue, therefore, could be positive for the patient and bad news for the virus.”
In the study, visceral adipocytes were exposed to different strains of SARS-CoV-2: the ancestral lineage originally from Wuhan, China, and isolated from one of the first Brazilians diagnosed with COVID-19; and the gamma variant (P.1.), which emerged in late 2020 in Manaus, the capital of Amazonas state in Brazil. The difference in susceptibility compared to subcutaneous adipocytes was observed only in response to the ancestral virus.
Dr Mori commented, "Our study team concluded that the Manaus variant is less effective at infecting visceral fat cells than the ancestral strain. A proteomic analysis of all the proteins produced by the cells showed that the Wuhan strain led to a reduction in several proteins associated with the cellular response to interferon (an immune system mechanism to combat viruses), whereas the gamma variant led to an increase. In other words, the Manaus strain made adipocytes produce more proteins that promote an antiviral response."
Interestingly, recent studies point to a downtrend in the number of severe cases of COVID-19 due to novel variants among individuals with obesity.
Dr Mori explained, "This could be influenced by other factors, such as vaccination or prior infection. Or these individuals may have been taking extra care because they knew they belonged to a high-risk group.”
In order to try to deepen their understanding of all these processes, the study team plans further experiments involving adipocytes cultured with the delta and omicron variants.
Also, another target for future research is to investigate possible medium- to long-term metabolic impacts of infection by SARS-CoV-2.
Dr Mori added, "Out team wants to find out whether infection changes the risk of developing diabetes or cardiovascular disease, for example. One way of doing so could be to analyze samples from patients who had COVID-19 and were later submitted to bariatric surgery, in order to see if morphological and functional alterations occurred in visceral adipose tissue as a result of the infection."
For the latest COVID-19 News
, keep on logging to Thailand Medical News.