Association of high level gene expression of ACE2 in adipose tissue with mortality of COVID-19 infection in obese patients

Abstract

Introduction Obese patients have an increased risk of COVID-19 critical illness leading to ICU admission or death compared to normal weight individuals. SARS-CoV-2 binding to angiotensin-converting enzyme 2 (ACE2) receptor is a critical step mediate virus entry into target cells. Articles have alluded that the level of ACE2 gene expression in adipose tissue is higher than lung tissue, but a PubMed search found no results in articles to demonstrate this. The aim of this study was to investigate ACE2 gene expression in adipose tissue and lung tissue using a public database. Material and methods A search of a public gene expression database to investigate ACE2 gene expression in human tissues. Results ACE2 gene expression was present in both visceral and subcutaneous adipose tissues. The gene expression profile demonstrated that ACE2 gene expression was higher in human visceral and subcutaneous adipose tissues than human lung tissue. Conclusion This study demonstrates that ACE2 gene expression is higher in visceral and subcutaneous adipose tissue than that in lung tissue, a major target tissue affected by SARS-CoV-2 infection. This suggests a mechanism by which excess adiposity may drive greater infection severity in patients with COVID-19.

Metformin use is associated with reduced mortality rate from coronavirus disease 2019 (COVID-19) infection

“…Therefore, inhibition of mTOR signaling by metformin may result in a reduction of SARS-CoV-2 infectivity and mortality from COVID-19 infection ( Sharma et al, 2020 ). Finally, through activation of AMPK, metformin can inhibit the inflammatory response that could potentially contribute to mortality through mechanism such as cytokine storm and vascular damage ( Singh et al, 2020 ; Al-Benna, 2020 ). Therefore, metformin use will decrease the inflammatory response, reducing the incidence of cytokine storm or vascular damage and finally lead to reduction in mortality rate.…”

Obesity and diabetes as comorbidities for COVID-19: Underlying mechanisms and the role of viral–bacterial interactions

“…ACE2 has at least three functions: it negatively regulates RAS, facilitates the transport of amino acids through association with amino acid transporters and also serves as a functional receptor for SARS-CoV/CoV-2. This enzyme is widely expressed in different organs and tissues, including lungs and AT ( Kruglikov and Scherer, 2020 ; Al-Benna, 2020 ). Expression of ACE2 in the host cells provides the possibility to modify Ang II to Ang-(1-7), which in turn is a vasodilating agent counteracting the vasoconstricting effect of Ang II through its binding to the Mas receptor.…”

“…In the obese and diabetic state, adipose tissue (AT) is compromised and can directly or indirectly be involved in interactions with SARS-CoV-2 at several levels. In the case of direct interactions with the virus, AT, demonstrating higher expression of ACE2 (especially in visceral depots) compared to the lungs ( Kruglikov and Scherer, 2020 ; Al-Benna, 2020 ), can serve as a big reservoir for viral infections ( Kruglikov and Scherer, 2020 ). A recent in vitro study (Institute of Biology, University of Campinas, Brazil) confirms that the SARS-CoV-2 virus can infect adipocytes where the virus can persist for extended periods of time ( https://agencia.fapesp.br/adipose-tissue-may-be-a-reservoir-for-sars-cov-2-brazilian-researchers-suggest/33729/ ).…”

SARS-CoV-2 and mitochondrial health: implications of lifestyle and ageing

“…Perhaps of relevance to the increased risk associated with obesity is that high ACE2 expression has been found in both visceral and subcutaneous adipose tissue; this is important as adipose tissue in obesity is well known to secrete higher levels of angiotensin 2, an inflammatory component of the renin-angiotensin aldosterone system (RAAS), which is key in driving many of the pathological complications associated with this condition [ 53 ]. Critically, obesity also seems to be associated with increased expression of ACE2 in the lung, and enhanced inflammatory markers and dysregulated lipogenesis; viruses are well known to hijack lipid metabolism as part of their life cycle [ 54 ].…”