PT  - JOURNAL ARTICLE
AU  - Saba Al Heialy
AU  - Mahmood Hachim
AU  - Abiola Senok
AU  - Ahmad Abou Tayoun
AU  - Rifat Hamoudi
AU  - Alawi Alsheikh-Ali
AU  - Qutayba Hamid
TI  - Regulation of angiotensin converting enzyme 2 (ACE2) in obesity: implications for COVID-19
AID  - 10.1101/2020.04.17.046938
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.17.046938
4099  - http://biorxiv.org/content/early/2020/04/18/2020.04.17.046938.short
4100  - http://biorxiv.org/content/early/2020/04/18/2020.04.17.046938.full
AB  - 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 regulation of inflammation and inhibition of leptin signaling. This is of interest as viruses may hijack host lipid metabolism to allow completion of their viral replication cycles. Furthermore, 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. Together our 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.Competing Interest StatementThe authors have declared no competing interest.