# ACE2-Mediated Infection of Immortalized Human Visceral Adipocytes by SARS-CoV-2

## TL;DR

This study shows that SARS-CoV-2 can infect human visceral fat cells through the ACE2 receptor, which may explain why obesity worsens COVID-19.

## Contribution

The study experimentally confirms that ACE2 is the receptor for SARS-CoV-2 infection in visceral adipocytes.

## Key findings

- Visceral adipocytes express higher ACE2 levels and are more susceptible to SARS-CoV-2 infection than subcutaneous adipocytes.
- ACE2 knockout reduces SARS-CoV-2 infection, while overexpression increases it and promotes a proinflammatory response.
- Increased ACE2 levels in visceral adipocytes correlate with higher viral transcript levels and IL6 induction over time.

## Abstract

Adipocytes can be infected by SARS-CoV-2, potentially contributing to the obesity-associated severity of COVID-19. Circumstantial evidence points to angiotensin-converting enzyme 2 (ACE2) as the necessary receptor for adipocyte infection, but this has not been demonstrated experimentally. Using differentiated immortalized human preadipocyte lines that we developed, we found that visceral adipocytes express higher levels of ACE2 and are more susceptible to SARS-CoV-2 spike (S)-mediated luciferase-VSV infection than subcutaneous adipocytes. Overexpression of ACE2 significantly increased infection, whereas knockout of ACE2 significantly decreased S-mediated infection. Visceral adipocytes at baseline were susceptible to infection by SARS-CoV-2 (Delta variant); however, increased levels of viral transcript with time were not apparent. ACE2 knockout significantly decreased the susceptibility of visceral adipocytes to SARS-CoV-2, whereas overexpression of ACE2 resulted in increased SARS-CoV-2 infection and was associated with increased viral transcript levels with time, as well as induction of IL6, a marker of the proinflammatory response. Our results demonstrate that ACE2 confers susceptibility to SARS-CoV-2 infection of visceral adipocytes. Higher levels of ACE2 in these cells may play a role in establishment of infection and a proinflammatory response, potentially leading to pathogenesis.