@article{7ceffc60c46147a188d940331ac844c3,
title = "ACE2 expression in adipose tissue is associated with cardio-metabolic risk factors and cell type composition-implications for COVID-19",
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.",
author = "{El-Sayed Moustafa}, {Julia S} and Jackson, {Anne U} and Brotman, {Sarah M} and Li Guan and Sergio Villica{\~n}a and Roberts, {Amy L} and Antonino Zito and Lori Bonnycastle and Erdos, {Michael R} and Narisu Narisu and Stringham, {Heather M} and Ryan Welch and Tingfen Yan and Timo Lakka and Stephen Parker and Jaakko Tuomilehto and Jeffrey Seow and Carl Graham and Isabella Huettner and Sam Acors and Neophytos Kouphou and Samuel Wadge and Duncan, {Emma L} and Steves, {Claire J} and Doores, {Katie J} and Malim, {Michael H} and Collins, {Francis S} and P{\"a}ivi Pajukanta and Michael Boehnke and Koistinen, {Heikki A} and Markku Laakso and Mario Falchi and Bell, {Jordana T} and Scott, {Laura J} and Mohlke, {Karen L} and Small, {Kerrin S}",
note = "Funding Information: KSS acknowledges funding from the Medical Research Council (MR/M004422/1 and MR/R023131/1). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health and Care Research (NIHCR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust in partnership with King{\textquoteright}s College London. The FUSION and METSIM studies were supported by US National Institutes of Health (NIH) grants U01DK062370, 1-ZIA-HG000024, R01DK093757, R01DK072193, P01HL28481, and Academy of Finland Grants 271961, 272741 and 258753. SMB was supported in part by a grant from the National Institute of General Medical Sciences under award 5T32 GM007092 and acknowledges the Global Partnership Award and UNC Global for travel funds. SV is supported by the National Council of Science and Technology of Mexico (CONACYT). SARS-CoV-2 serological analyses were supported by a COVID urgent response grant from the Chronic Disease Research Foundation (CDRF, CJS) and a King{\textquoteright}s Together Rapid COVID-19 Call award (MHM, KJD, CJS). Questionnaire material for the assessment of COVID-19 symptoms was developed as part of the Wellcome Longitudinal Population Study COVID-19 Steering Group and Secretariat (supported by Wellcome funding 221574/Z/20/Z). Data on TwinsUK participants are available to bona fide researchers under managed access due to governance and ethical constraints. Raw data should be requested via our website ( https://twinsuk.ac.uk/resources-for-researchers/access-our-data/ ) and requests are reviewed by the TwinsUK Resource Executive Committee (TREC) regularly. The authors acknowledge use of the research computing facility at King{\textquoteright}s College London, Rosalind ( https://rosalind.kcl.ac.uk ), which is delivered in partnership with the National Institute for Health Research (NIHR) Biomedical Research Centres at South London & Maudsley and Guy{\textquoteright}s & St. Thomas{\textquoteright} NHS Foundation Trusts, and part-funded by capital equipment grants from the Maudsley Charity (award 980) and Guy{\textquoteright}s & St. Thomas{\textquoteright} Charity (TR130505). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHCR, King{\textquoteright}s College London, or the Department of Health and Social Care. The authors thank Dr. J{\"o}rg Sa{\ss}mannshausen and Dr Lukasz Zalweski from the Rosalind support team for their computational support. Funding Information: KSS acknowledges funding from the Medical Research Council (MR/M004422/1 and MR/R023131/1). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health and Care Research (NIHCR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust in partnership with King{\textquoteright}s College London. The FUSION and METSIM studies were supported by US National Institutes of Health (NIH) grants U01DK062370, 1-ZIA-HG000024, R01DK093757, R01DK072193, P01HL28481, and Academy of Finland Grants 271961, 272741 and 258753. SMB was supported in part by a grant from the National Institute of General Medical Sciences under award 5T32 GM007092 and acknowledges the Global Partnership Award and UNC Global for travel funds. SV is supported by the National Council of Science and Technology of Mexico (CONACYT). SARS-CoV-2 serological analyses were supported by a COVID urgent response grant from the Chronic Disease Research Foundation (CDRF, CJS) and a King{\textquoteright}s Together Rapid COVID-19 Call award (MHM, KJD, CJS). Questionnaire material for the assessment of COVID-19 symptoms was developed as part of the Wellcome Longitudinal Population Study COVID-19 Steering Group and Secretariat (supported by Wellcome funding 221574/Z/20/Z). Data on TwinsUK participants are available to bona fide researchers under managed access due to governance and ethical constraints. Raw data should be requested via our website (https://twinsuk.ac.uk/resources-for-researchers/access-our-data/) and requests are reviewed by the TwinsUK Resource Executive Committee (TREC) regularly. The authors acknowledge use of the research computing facility at King{\textquoteright}s College London, Rosalind (https://rosalind.kcl.ac.uk), which is delivered in partnership with the National Institute for Health Research (NIHR) Biomedical Research Centres at South London & Maudsley and Guy{\textquoteright}s & St. Thomas{\textquoteright} NHS Foundation Trusts, and part-funded by capital equipment grants from the Maudsley Charity (award 980) and Guy{\textquoteright}s & St. Thomas{\textquoteright} Charity (TR130505). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHCR, King{\textquoteright}s College London, or the Department of Health and Social Care. The authors thank Dr. J{\"o}rg Sa{\ss}mannshausen and Dr Lukasz Zalweski from the Rosalind support team for their computational support. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = aug,
doi = "10.1038/s41366-022-01136-w",
language = "English",
volume = "46",
pages = "1478--1486",
journal = "International Journal of Obesity",
issn = "0307-0565",
publisher = "Springer Nature [academic journals on nature.com]",
number = "8",
}
