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. 2020 Jul 1;319(1):E43-E47.
doi: 10.1152/ajpendo.00219.2020. Epub 2020 May 29.

SARS-CoV-2 perturbs the renin-angiotensin system and energy metabolism

Jun Mori  1 , Gavin Y Oudit  2   3   4 , Gary D Lopaschuk  4   5   6
Affiliations

SARS-CoV-2 perturbs the renin-angiotensin system and energy metabolism

Jun Mori et al. Am J Physiol Endocrinol Metab. .

Abstract

The COVID-19 pandemic, caused by the novel coronavirus, SARS-CoV-2, is threating our health systems and daily lives and is responsible for causing substantial morbidity and mortality. In particular, aged individuals and individuals with comorbidities, including obesity, diabetes mellitus, and hypertension, have significantly higher risks of hospitalization and death than normal individuals. The renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of diabetes mellitus, obesity, and hypertension. Angiotensin-converting enzyme 2 (ACE2), belonging to the RAS family, has received much attention during this COVID-19 pandemic, owing to the fact that SARS-CoV-2 uses ACE2 as a receptor for cellular entry. Additionally, the RAS greatly affects energy metabolism in certain pathological conditions, including cardiac failure, diabetes mellitus, and viral infections. This article discusses the potential mechanisms by which SARS-CoV-2 modulates the RAS and energy metabolism in individuals with obesity and diabetes mellitus. The article aims to highlight the appropriate strategies for combating the COVID-19 pandemic in the clinical setting and emphasize on the areas that require further investigation in relation to COVID-19 infections in patients with obesity and diabetes mellitus from the viewpoint of endocrinology and metabolism.

Keywords: RAS; SARS-CoV-2; energy metabolism; obesity.

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Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

Fig. 1.
Fig. 1.
Balance between the angiotensin-converting enzyme (ACE)-angiotensin II (Ang II)-angiotensin 1 receptor (AT1R) axis and the ACE2-Ang 1–7-Mas receptor axis. A: ACE2 converts Ang II to Ang 1–7. B: Ang II binds to AT1R and induces numerous detrimental effects, including vasoconstriction, production of reactive oxygen species (ROS), hypertrophy, and fibrosis. C: Ang 1–7 binds to the Mas receptor and induces protective effects and counteracts the ACE-Ang II-AT1R axis. D: ADAM17 mediates the shedding of the ectodomain of ACE2.
Fig. 2.
Fig. 2.
Role of angiotensin-converting enzyme 2 (ACE2) in the pathogenesis of SARS-CoV-2 infections. A: healthy condition. There is a balance between angiotensin II (Ang II)/AT1R and Ang 1–7/MasR. B: infection status. SARS-CoV-2 enters the cell by binding to the ACE2 receptor. The endocytosis of SARS-CoV-2 activates ADAM17, leading to a reduction in ACE2 activity and a shift from Ang 1–7 to Ang II.
Fig. 3.
Fig. 3.
Effects of SARS-CoV-2 infections on energy metabolism. A: healthy condition. B: SARS-CoV-2 infections increase the levels of angiotensin II (Ang II) and decrease the levels of Ang 1–7, which subsequently downregulates the activity of pyruvate dehydrogenase complex (PDC). The reduction in the activity of PDC decreases the rate of glycolysis, resulting in uncoupling between glycolysis and glucose oxidation. This uncoupling induces intracellular acidosis and energy depletion. Yellow arrow, fatty acid β-oxidation; pink arrow, glycolysis; blue arrow, glucose oxidation. Ac, acetylation; P, phosphorylation.
See this image and copyright information in PMC

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