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

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), transmem-brane 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.