Abstract
The ongoing COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. Age, smoking, obesity, and chronic diseases such as cardiovascular disease and diabetes have been described as risk factors for severe complications and mortality in COVID-19. Obesity and diabetes are usually associated with dysregulated lipid synthesis and clearance, which can initiate or aggravate pulmonary inflammation and injury. It has been shown that for viral entry into the host cell, SARS-CoV-2 utilizes the angiotensin-converting enzyme 2 (ACE2) receptors present on the cells. We aimed to characterize how SARS-CoV-2 dysregulates lipid metabolism pathways in the host and the effect of dysregulated lipogenesis on the regulation of ACE2, specifically in obesity. In our study, through the re-analysis of publicly available transcriptomic data, we first found that lung epithelial cells infected with SARS-CoV-2 showed upregulation of genes associated with lipid metabolism, including the SOC3 gene, which is involved in the regulation of inflammation and inhibition of leptin signaling. This is of interest as viruses may hijack host lipid metabolism to allow the completion of their viral replication cycles. Furthermore, a dataset using a mouse model of diet-induced obesity showed a significant increase in Ace2 expression in the lungs, which negatively correlated with the expression of genes that code for sterol response element-binding proteins 1 and 2 (SREBP). Suppression of Srebp1 showed a significant increase in Ace2 expression in the lung. Moreover, ACE2 expression in human subcutaneous adipose tissue can be regulated through changes in diet. Validation of the in silico data revealed a higher expression of ACE2, TMPRSS2 and SREBP1 in vitro in lung epithelial cells from obese subjects compared to non-obese subjects. To our knowledge this is the first study to show upregulation of ACE2 and TMPRSS2 in obesity. In silico and in vitro results suggest that the dysregulated lipogenesis and the subsequently high ACE2 expression in obese patients might be the mechanism underlying the increased risk for severe complications in those patients when infected by SARS-CoV-2.
Highlights
As the COVID-19 pandemic continues, people worldwide are warned to take necessary precautions to avoid infection
The top pathways where the differentially expressed genes (DEGs) by SARS-CoV-2 are involved were related to inflammatory, immune, cytokines, and antiviral responses
Our re-analysis of the publicly available transcriptomic datasets demonstrated that SARS-CoV-2 infection of healthy epithelial cells compared to mock-infected cells clusters the genes involved in inflammatory, immune and viral responses (Figure 1)
Summary
As the COVID-19 pandemic continues, people worldwide are warned to take necessary precautions to avoid infection. It is well established that obesity leads to chronic meta-inflammation even in the absence of infection, which has detrimental effects on the immune system such as polarization of macrophages toward a pro-inflammatory phenotype termed M1 macrophages (Li et al, 2018). During the H1N1 pandemic in 2009, obesity was classified as an independent risk factor for hospitalization, need for mechanical ventilation, and death (Morgan et al, 2010). These observations are concerning since over one-third of the world population are classified as overweight or obese (Hruby and Hu, 2015). Understanding the effects of obesity on COVID-19 may shed light on the pathogenicity of SARS-CoV-2
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
