Obesity and COVID-19: the ominous duet affecting the renin-angiotensin system

Luzi, Livio; Bucciarelli, Loredana; Ferrulli, Anna; Terruzzi, Ileana; Massarini, Stefano

doi:10.23736/s2724-6507.20.03402-1

Cited by 11 publications

(16 citation statements)

References 65 publications

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“…Obesity is characterized by an expansion in white adipose tissue (WAT) mass and is linked to a number of comorbidities, including hypertension and diabetes [1]. More recently, obesity has emerged as a major risk factor for severe illness related to COVID-19 infection [2,3]. Infection with the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) occurs mainly through the airway [4].…”

Section: Introductionmentioning

confidence: 99%

“…Under conditions of hypertension and obesity, hyperactivation of the RAS leads to inflammation, fibrosis and oxidative damage [8]. In this context, therapies aimed at increasing flux through the counterregulatory arm of the RAS have gained attention as a potential treatment for hypertension and obesity [2,8]. These effects are mainly mediated by ACE2, which converts Ang-II into Ang(1,7) [8].…”

Section: Introductionmentioning

confidence: 99%

“…Ang (1,7) binds to the Mas receptor (MasR), which exerts protective, anti-inflammatory effects [9]. Moreover, Ang-II can also bind to angiotensin II, type 2 receptor (AT 2 R) [2]. AT 2 R exerts similar effects to MasR, however it is mainly expressed under conditions of AT 1 R hyperactivation and injury to suppress inflammation and oxidative stress [2,11].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, Ang-II can also bind to angiotensin II, type 2 receptor (AT 2 R) [2]. AT 2 R exerts similar effects to MasR, however it is mainly expressed under conditions of AT 1 R hyperactivation and injury to suppress inflammation and oxidative stress [2,11]. Following COVID infection, ACE2 becomes downregulated [2].…”

Section: Introductionmentioning

confidence: 99%

“…AT 2 R exerts similar effects to MasR, however it is mainly expressed under conditions of AT 1 R hyperactivation and injury to suppress inflammation and oxidative stress [2,11]. Following COVID infection, ACE2 becomes downregulated [2]. Consequently, the obesity-induced elevation in Ang-II increases signalling through AT 1 R, which promotes inflammation and tissue damage [2].…”

Section: Introductionmentioning

confidence: 99%

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Obesogenic and Ketogenic Diets Distinctly Regulate the SARS-CoV-2 Entry Proteins ACE2 and TMPRSS2 and the Renin-Angiotensin System in Rat Lung and Heart Tissues

2021

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Background: Obesity increases the severity of SARS-CoV-2 outcomes. Thus, this study tested whether obesogenic and ketogenic diets distinctly affect SARS-CoV-2 entry proteins and the renin-angiotensin system (RAS) in rat pulmonary and cardiac tissues. Methods: Male Sprague-Dawley rats were fed either standard chow (SC), a high-fat sucrose-enriched diet (HFS), or a ketogenic diet (KD) for 16 weeks. Afterwards, levels of angiotensin converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), RAS components, and inflammatory genes were measured in the lungs and hearts of these animals. Results: In the lungs, HFS elevated ACE2 and TMPRSS2 levels relative to SC diet, whereas the KD lowered the levels of these proteins and the gene expressions of toll-like receptor 4 and interleukin-6 receptor relative to HFS. The diets did not alter ACE2 and TMPRSS2 in the heart, although ACE2 was more abundant in heart than lung tissues. Conclusion: Diet-induced obesity increased the levels of viral entry proteins in the lungs, providing a mechanism whereby SARS-CoV-2 infectivity can be enhanced in obese individuals. Conversely, by maintaining low levels of ACE2 and TMPRSS2 and by exerting an anti-inflammatory effect, the KD can potentially attenuate the severity of infection and migration of SARS-CoV-2 to other ACE2-expressing tissues.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Obesogenic and Ketogenic Diets Distinctly Regulate the SARS-CoV-2 Entry Proteins ACE2 and TMPRSS2 and the Renin-Angiotensin System in Rat Lung and Heart Tissues

2021

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Interaction effects between angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers and steroid or antiviral therapies in COVID‐19: A population‐based study

Zhou

Tse²,

Lee

et al. 2021

Journal of Medical Virology

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To the Editor,We read the recent article published in your journal on the predictors of mortality in patients with coronavirus 2019 infection with great interest. 1 In that study, treatment with antibiotics, antifungals, antivirals, steroids, blood transfusion, and intubation was associated with increased mortality. Indeed, whether steroids have beneficial effects on mortality in COVID-19 remains controversial. 2 There may also be interactions between steroids and the renin-angiotensin-aldosterone system as well as differential effects between angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in COVID-19 outcomes. 3 The benefit of ACEIs/ARBs has also been controversial [4][5][6] and the association with worse outcomes may partly be explained by the presence of comorbidities. 7,8 Therefore, using a local population-based administrative health record system, we examined the interaction effects between the use of ACEIs or ARBs with steroids or antiviral therapies on severe disease outcome in COVID-19 patients.

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Interaction of ACEI antihypertensive agent's administration with the inflammatory status at admission concerning COVID-19 clinical stay outcomes

Martínez-Urbistondo

Moreno-Torres

Mora-Vargas

et al. 2022

Vascular Pharmacology

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Interactions between anti-hypertensive agents (ACEI), comorbidities, inflammation, and stress status may impact hospital stay duration in COVID-19 patients. This retrospective study analyzed epidemiological data, comorbidities, metabolic/inflammatory markers, and clinical information from 165 SARS-CoV-2 positive patients. In a multiple linear regression model, an IL-6 higher than 100 mg/L, glucose at admission (baseline levels at the hospital entry), and the interaction between ACEI administration and LDH predicted the days of hospital admission (P < 0.001). In conclusion, hypertensive patients suffering more severe inflammatory condition assessed by LDH levels clinically benefited more and reduced the hospital stay when prescribed ACEI agents than those with lower systemic baseline inflammation at admission.

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Obesity and COVID-19: the ominous duet affecting the renin-angiotensin system

Cited by 11 publications

References 65 publications

Obesogenic and Ketogenic Diets Distinctly Regulate the SARS-CoV-2 Entry Proteins ACE2 and TMPRSS2 and the Renin-Angiotensin System in Rat Lung and Heart Tissues

Obesogenic and Ketogenic Diets Distinctly Regulate the SARS-CoV-2 Entry Proteins ACE2 and TMPRSS2 and the Renin-Angiotensin System in Rat Lung and Heart Tissues

Interaction effects between angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers and steroid or antiviral therapies in COVID‐19: A population‐based study

Interaction of ACEI antihypertensive agent's administration with the inflammatory status at admission concerning COVID-19 clinical stay outcomes

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