Metabolic impact of weight loss induced reduction of adipose ACE-2 - Potential implication in COVID-19 infections?

doi:10.1016/j.metabol.2020.154401

Randomized Controlled Trial

. 2020 Dec:113:154401.

doi: 10.1016/j.metabol.2020.154401. Epub 2020 Oct 13.

Metabolic impact of weight loss induced reduction of adipose ACE-2 - Potential implication in COVID-19 infections?

Linna Li¹, Leonard Spranger², Dominik Soll², Finja Beer², Maria Brachs³, Joachim Spranger⁴, Knut Mai⁵

Affiliations

¹ Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Clinical Research Unit, 10117 Berlin, Germany.
² Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany.
³ Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité Center for Cardiovascular Research, 10117 Berlin, Germany.
⁴ Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité Center for Cardiovascular Research, 10117 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany. Electronic address: joachim.spranger@charite.de.
⁵ Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité Center for Cardiovascular Research, 10117 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Clinical Research Unit, 10117 Berlin, Germany.

PMID: 33065163
PMCID: PMC7552972
DOI: 10.1016/j.metabol.2020.154401

Randomized Controlled Trial

Metabolic impact of weight loss induced reduction of adipose ACE-2 - Potential implication in COVID-19 infections?

Linna Li et al. Metabolism. 2020 Dec.

. 2020 Dec:113:154401.

doi: 10.1016/j.metabol.2020.154401. Epub 2020 Oct 13.

Authors

Linna Li¹, Leonard Spranger², Dominik Soll², Finja Beer², Maria Brachs³, Joachim Spranger⁴, Knut Mai⁵

Affiliations

¹ Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Clinical Research Unit, 10117 Berlin, Germany.
² Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany.
³ Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité Center for Cardiovascular Research, 10117 Berlin, Germany.
⁴ Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité Center for Cardiovascular Research, 10117 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany. Electronic address: joachim.spranger@charite.de.
⁵ Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Endocrinology and Metabolism, 10117 Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité Center for Cardiovascular Research, 10117 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Clinical Research Unit, 10117 Berlin, Germany.

PMID: 33065163
PMCID: PMC7552972
DOI: 10.1016/j.metabol.2020.154401

Abstract

Background & aims: Angiotensin converting enzyme (ACE)-2 is a modulator of adipose tissue metabolism. However, human data of adipose ACE-2 is rarely available. Considering that, ACE-2 is believed to be the receptor responsible for cell entry of SARS-CoV-2, a better understanding of its regulation is desirable. We therefore characterized the modulation of subcutaneous adipose ACE-2 mRNA expression during weight loss and the impact of ACE-2 expression on weight loss induced short- and long-term improvements of glucose metabolism.

Methods: 143 subjects (age > 18; BMI ≥ 27 kg/m²) were analyzed before and after a standardized 12-week dietary weight reduction program. Afterwards subjects were randomized to a 12-month lifestyle intervention or a control group (Maintain-Adults trial). Insulin sensitivity (IS) was estimated by HOMA-IR (as an estimate of liver IS) and ISI_Clamp (as an estimate of skeletal muscle IS). ACE-2 mRNA expression (ACE-2_AT) was measured in subcutaneous adipose tissue before and after weight loss.

Results: ACE-2_AT was not affected by obesity, but was reduced in insulin resistant subjects. Weight loss resulted in a decline of ACE-2_AT (29.0 (20.0-47.9) vs. 21.0 (13.0-31.0); p = 1.6 ∗ 10^-7). A smaller reduction of ACE-2 _AT (ΔACE-2_AT) was associated with a larger improvement of ISI_Clamp (p = 0.013) during weight reduction over 3 months, but not with the extend of weight loss. The degree of changes in insulin resistance were preserved until month 12 and was also predicted by the weight loss induced degree of ΔACE-2_AT (p = 0.011).

Conclusions: Our data indicate that subcutaneous adipose ACE-2 expression correlates with insulin sensitivity. Weight loss induced decline of subcutaneous adipose ACE-2 expression might affect short- and long-term improvement of myocellular insulin sensitivity, which might be also relevant in the context of ACE-2 downregulation by SARS-CoV-2.

Trial registration: ClinicalTrials.gov number: NCT00850629, https://clinicaltrials.gov/ct2/show/NCT00850629, date of registration: February 25, 2009.

Keywords: ACE-2; Adipose tissue; Insulin sensitivity; Obesity; Weight loss.

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Conflict of interest statement

Declaration of competing interest We declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Figures

**Fig. 1**
Association of weight loss induced changes of ACE-2_AT with ΔISI_Clamp during weight loss.

See this image and copyright information in PMC

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References

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[1] Zhu L., She Z.G., Cheng X., Qin J.J., Zhang X.J., Cai J. Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes. Cell Metab. 2020;31(6):1068–77 e3. doi: 10.1016/j.cmet.2020.04.021. - DOI - PMC - PubMed

[2] Zhu L., She Z.G., Cheng X., Qin J.J., Zhang X.J., Cai J. Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes. Cell Metab. 2020;31(6):1068–77 e3. doi: 10.1016/j.cmet.2020.04.021. - DOI - PMC - PubMed

[3] Argenziano M.G., Bruce S.L., Slater C.L., Tiao J.R., Baldwin M.R., Barr R.G. Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series. BMJ. 2020;369 doi: 10.1136/bmj.m1996. - DOI - PMC - PubMed

[4] Argenziano M.G., Bruce S.L., Slater C.L., Tiao J.R., Baldwin M.R., Barr R.G. Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series. BMJ. 2020;369 doi: 10.1136/bmj.m1996. - DOI - PMC - PubMed

[5] Kalligeros M., Shehadeh F., Mylona E.K., Benitez G., Beckwith C.G., Chan P.A. Association of obesity with disease severity among patients with COVID-19. Obesity (Silver Spring) 2020 doi: 10.1002/oby.22859. - DOI - PMC - PubMed

[6] Kalligeros M., Shehadeh F., Mylona E.K., Benitez G., Beckwith C.G., Chan P.A. Association of obesity with disease severity among patients with COVID-19. Obesity (Silver Spring) 2020 doi: 10.1002/oby.22859. - DOI - PMC - PubMed

[7] Simonnet A., Chetboun M., Poissy J., Raverdy V., Noulette J., Duhamel A. High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation. Obesity (Silver Spring) 2020 doi: 10.1002/oby.22831. - DOI - PMC - PubMed

[8] Simonnet A., Chetboun M., Poissy J., Raverdy V., Noulette J., Duhamel A. High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation. Obesity (Silver Spring) 2020 doi: 10.1002/oby.22831. - DOI - PMC - PubMed

[9] Watanabe M., Caruso D., Tuccinardi D., Risi R., Zerunian M., Polici M. Visceral fat shows the strongest association with the need of intensive care in patients with COVID-19. Metabolism. 2020;111:154319. doi: 10.1016/j.metabol.2020.154319. - DOI - PMC - PubMed

[10] Watanabe M., Caruso D., Tuccinardi D., Risi R., Zerunian M., Polici M. Visceral fat shows the strongest association with the need of intensive care in patients with COVID-19. Metabolism. 2020;111:154319. doi: 10.1016/j.metabol.2020.154319. - DOI - PMC - PubMed

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Metabolic impact of weight loss induced reduction of adipose ACE-2 - Potential implication in COVID-19 infections?

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Metabolic impact of weight loss induced reduction of adipose ACE-2 - Potential implication in COVID-19 infections?

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