In:
International Journal of Obesity, Springer Science and Business Media LLC, Vol. 46, No. 8 ( 2022-08), p. 1478-1486
Abstract:
COVID-19 severity varies widely. Although some demographic and cardio-metabolic factors, including age and obesity, are associated with increasing risk of severe illness, the underlying mechanism(s) are uncertain. Subjects/methods In a meta-analysis of three independent studies of 1471 participants in total, we investigated phenotypic and genetic factors associated with subcutaneous adipose tissue expression of Angiotensin I Converting Enzyme 2 ( ACE2 ), measured by RNA-Seq, which acts as a receptor for SARS-CoV-2 cellular entry. Results Lower adipose tissue ACE2 expression was associated with multiple adverse cardio-metabolic health indices, including type 2 diabetes (T2D) ( P = 9.14 × 10 −6 ), obesity status ( P = 4.81 × 10 −5 ), higher serum fasting insulin ( P = 5.32 × 10 −4 ), BMI ( P = 3.94 × 10 −4 ), and lower serum HDL levels ( P = 1.92 × 10 −7 ). ACE2 expression was also associated with estimated proportions of cell types in adipose tissue: lower expression was associated with a lower proportion of microvascular endothelial cells ( P = 4.25 × 10 −4 ) and higher proportion of macrophages ( P = 2.74 × 10 −5 ). Despite an estimated heritability of 32%, we did not identify any proximal or distal expression quantitative trait loci (eQTLs) associated with adipose tissue ACE2 expression. Conclusions Our results demonstrate that individuals with cardio-metabolic features known to increase risk of severe COVID-19 have lower background ACE2 levels in this highly relevant tissue. Reduced adipose tissue ACE2 expression may contribute to the pathophysiology of cardio-metabolic diseases, as well as the associated increased risk of severe COVID-19.
Type of Medium:
Online Resource
ISSN:
0307-0565
,
1476-5497
DOI:
10.1038/s41366-022-01136-w
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
2101927-7
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