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.

Daniel Da Eira,Shailee Jani,Rolando B Ceddia

doi:10.3390/nu13103357

Abstract

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.

Highlights

Our study aims to compare the effects of different dietary interventions on the contents of viral entry proteins and renin-angiotensin system (RAS)
Weighing 200–250 g—were maintained in a constant-temperature (23 ◦ C), with a fixed 12-h light/12-h dark cycle and fed for 16 weeks ad libitum either a standard chow diet (SC, 27.0%, 13.0%, and 60.0% of calories provided by protein, fat, and carbohydrates, respectively) a HF, sucrose-enriched (HFS) diet (20.0%, 60.0%, and 20.0% of calories provided by protein, fat, and carbohydrates [sucrose], respectively) or a ketogenic diet (KD)
Here,we weshow showthat thatobesogenic obesogenicand andketogenic ketogenicdiets dietsregulate regulateininaadistinct distinctand andtissuetissueHere, specific manner proteins of the RAS, as well as major components of the molecular maspecific manner proteins of the RAS, as well as major components of the molecular machinery involved in cellular infection by SARS-CoV-2

Summary

Introduction

The interaction between ACE2 and SARS-CoV-2 occurs via the virus’s spike (S) protein; an additional crucial step, catalysed by transmembrane protease serine 2 (TMPRSS2), leads to cleavage of the S protein [4,5]. The enhanced susceptibility of obese individuals to severe COVID19 outcomes has been linked to elevations in ACE2 and TMPRSS2 in lung tissues [4,7]. Batchu et al reported elevations in ACE2 and TMPRSS2 protein contents in the lungs of HF-fed, diabetic mice [7] In this context, the diet-induced elevations in SARS-CoV-2 entry proteins provide a plausible mechanism that explains the increased susceptibility of obese individuals to severe outcomes. 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. 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

Methods

Results

Conclusion