ACE2 expression in adipose tissue is associated with cardio-metabolic risk factors and cell type composition-implications for COVID-19

Julia S El-Sayed Moustafa, Anne U Jackson, Sarah M Brotman, Li Guan, Sergio Villicaña, Amy L Roberts, Antonino Zito, Lori Bonnycastle, Michael R Erdos, Narisu Narisu, Heather M Stringham, Ryan Welch, Tingfen Yan, Timo Lakka, Stephen Parker, Jaakko Tuomilehto, Jeffrey Seow, Carl Graham, Isabella Huettner, Sam AcorsNeophytos Kouphou, Samuel Wadge, Emma L Duncan, Claire J Steves, Katie J Doores, Michael H Malim, Francis S Collins, Päivi Pajukanta, Michael Boehnke, Heikki A Koistinen, Markku Laakso, Mario Falchi, Jordana T Bell, Laura J Scott, Karen L Mohlke, Kerrin S Small

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

BACKGROUND: 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.

Original languageEnglish
Pages (from-to)1478-1486
Number of pages9
JournalInternational Journal of Obesity
Volume46
Issue number8
Early online date20 May 2022
DOIs
Publication statusPublished - Aug 2022

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