Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.B1 (
angiotensin-converting enzyme 2
)
1,025
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Regulation of Angiotensin- Converting Enzyme 2 in Obesity: Implications for COVID-19. 3307 15
