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Principal Investigator: TRACEY MCLAUGHLIN
Organization: STANFORD UNIVERSITY
Fiscal Year: 2021
Award: $236,175
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY/ABSTRACT
Obesity is a major risk factor for severe outcomes in Covid-19, exceeding the risk associated with type 2 diabetes
and hypertension by 3-fold. The underlying reason is unknown. While obese individuals may have an impaired
immune response or a predilection towards inflammation, hypertension, and cardiac decompensation due to
underlying metabolic syndrome, we hypothesize that a more specific mechanism is at play: ACE2, the receptor for
the spike protein on SARS-CoV-2 is highly expressed in subcutaneous and visceral adipose tissue, which may allow
for viral entry and replication. Particularly in peri-organ fat depots, inflammation, vasoconstriction and fibrosis as a
consequence of viral infection and subsequent downregulation of ACE2 may contribute to organ damage including
heart, gut, liver, and kidney. As such, the goal of this project is to determine whether SARS-CoV-2 infects human
adipocytes from subcutaneous (SAT), visceral (VAT), epicardial (EAT), and paracardial adipose tissue (PAT),
whether infection incites inflammation, and whether pharmacologic compounds that target the renin-angiotensin
system (RAS)/ACE2 alter infectivity and inflammation.
1. Assess the ability of SARS-CoV-2 to infect adipocytes and/or other resident cells in adipose tissue (SAT, VAT,
EAT, PAT)
2. Profile the inflammatory response in adipose tissue cells exposed to SARS-CoV-2
3. Determine the ability of pharmacologic compounds that target RAS/ACE2 to inhibit infectivity and/or
inflammation
The results of this research will: 1) address a fundamental and critically-important question: does adipose tissue play a
role in the link between obesity and COVID-19, via increased infection and/or inflammation; and 2) evaluate the effects
of treatments targeting RAS/ACE2 that may mitigate infectivity and/or inflammation in adipose tissue.
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