Researchers studying young obese mice have found that expression of ACE2, a host cell receptor that binds to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is high in the lungs and trachea of obese mice. I found that. This finding may partially explain why obesity is a risk factor for COVID-19.
With the continued epidemic of COVID-19 caused by the SARS-CoV-2 virus, several studies have highlighted disease severity and risk factors for death. One of these factors is obesity.
How obesity affects disease progression is still controversial, and there are studies suggesting changes in lung function due to obesity, vascular health, or changes in the immune system.
The SARS-CoV-2 virus infects the host cell by binding to angiotensin converting enzyme 2 (ACE2) on the surface of the host cell. It is believed to be promoted by the expression of the serine protease TMPRSS2 by the host cell, which cleaves the spike protein for invasion. Both ACE2 and TMPRSS2 are expressed in different types of human cells, including the heart, lungs, kidneys, and liver.
The virus is thought to be the main route of the virus through the respiratory tract, as it primarily affects the respiratory system.
In a new survey published on the preprint server bioRxiv* In October 2020, researchers at Johns Hopkins University School of Medicine hypothesized that obesity could alter the expression of ACE2 and TMPRSS2 in the lower respiratory tract, increasing the risk of developing COVID-19. In addition, they also studied both male and female mice to understand the differences in COVID-19 severity and mortality between genders.
Obese mice show elevated ACE2 expression
The researchers tested the hypothesis in obese mice. They fed male and female mice a high-fat diet, with 60% of their calories derived from fat. Five months after this diet, the mice gained a lot of weight and fat.
They collected lungs, trachea, and esophagus from euthanized mice and isolated RNA from these organs. Real-time polymerase chain reaction (RT-PCR) was used to test levels of ACE2 and TMPRSS2.
Real-time PCR studies have shown high expression of ACE2 in the lungs and trachea of obese male mice compared to lean mice that acted as controls. In contrast, TMPRSS2 was reduced in the trachea of obese mice. There was no difference in ACE2 expression in the esophagus of obese and lean mice.
However, obese female mice had reduced ACE2 expression in obese mice compared to lean mice. Expression of TMPRSS2 was significantly reduced in the lungs of obese women and increased in the trachea.
There was also a difference in expression in male and female mice. In lean mice, females had higher expression of ACE2 in the lungs and esophagus than males. Women had higher lung TMPRSS2 expression and lower tracheal expression compared to lean men. There was no difference in TMPRSS2 expression in the esophagus of lean mice.
In obese mice, males had higher tracheal expression of ACE2 and lungs had higher TMPRSS2 expression than females, whereas females had higher tracheal TMPRSS2 expression.
Altered ACE2 expression may increase COVID-19 risk
Patients with COVID-19 who are experiencing severe symptoms have been found to have high viral load in the respiratory tract, and levels of ACE2 and TMPRSS2 are thought to be involved in viral load.
A meta-analysis of 75 published studies from more than 10 countries in Asia, Europe, and the Americas found that obesity is one of the highest risk factors for diagnosis and hospitalization of COVID-19 and a risk of death of 48. Found to be% higher. Men appear to have about 2.5% higher mortality than women.
Higher ACE2 expression in the trachea of obese male mice compared to lean and female mice could explain the higher risk of obese males. Obese men have low expression of TMPRSS2, but the virus can use other cellular proteases to invade host cells.
The author notes some limitations of the study. They quantified the expression of ACE2 and TMPRSS2 from tissue-wide bulk RNA. Therefore, they did not identify the source cells for their expression.
In addition, the mice they used in their studies were only 6 months old, which corresponds to young humans. However, deaths from COVID-19 have been found to be significantly higher in the elderly. Therefore, further research is needed on older mice to test how age affects ACE2 and TMPRSS2 expression.
bioRxiv Publish preliminary scientific reports that should not be considered definitive as they are not peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.
- Sarver, DC and Wong, GW (2020) obesity alters Ace2 and Tmprss2 expression in the lungs, trachea, and esophagus in a sex-dependent manner: effects on COVID-19. bioRxiv. https://doi.org/10.1101/2020.10.13.337907