Obesity‐Induced Metabolic Priming Exacerbates <scp>SARS</scp>‐<scp>CoV</scp>‐2 Inflammation
Despite the early recognition that individuals living with obesity are more prone to develop adverse outcomes during COVID-19, the mechanisms underlying these conditions are still unclear. During obesity, an accumulation of free fatty acids (FFAs) in the circulation promotes low-grade inflammation. Here, we show that FFAs induce epigenetic reprogramming of monocytes, exacerbating their inflammatory profile after SARS-CoV-2 infection, a mechanism named metabolic-primed immunity. Monocytes from people with obesity or primed with palmitate, a central component of circulating FFAs, presented elevated viral load and higher gene expression of IL-6. Palmitate-primed monocytes upregulate fatty acid oxidation and FFAs entry into the mitochondria. FFA-derived acetyl-CoA is then converted into citrate, exiting the mitochondria and is used to support H3K18 histone acetylation, which regulates IL-6 accessibility. Ingestion of palm oil by lean and healthy individuals increased circulating FFAs levels and was sufficient to exacerbate the inflammatory profile of monocytes upon SARS-CoV-2 infection. Our findings demonstrate that obesity-derived FFAs induce the metabolic priming of monocytes, which exacerbates the inflammatory response observed in people with severe COVID-19.
Authors
- Gisele Castro (ORCID: https://orcid.org/0000-0001-9965-5485)
- Mariane Font Fernandes (ORCID: https://orcid.org/0000-0002-0262-4509)
- José Luís Fachi (ORCID: https://orcid.org/0000-0002-1035-5193)
- Joseph W. Guarnieri (ORCID: https://orcid.org/0000-0001-7802-7826)
- Nathália Araujo (ORCID: https://orcid.org/0000-0002-1567-6332)
- Gabriela F Rodrigues-Luiz (ORCID: https://orcid.org/0000-0003-3838-1008)
- Íkaro Breder (ORCID: https://orcid.org/0000-0003-4787-9916)
- Adriana Leandra Santoro (ORCID: https://orcid.org/0000-0002-7208-5037)
- João Victor Virgílio-da-Silva (ORCID: https://orcid.org/0000-0002-7846-7386)
- Bianca Gazieri Castelucci (ORCID: https://orcid.org/0000-0003-1534-305X)
- Marcelo A. Mori (ORCID: https://orcid.org/0000-0001-7112-5263)
- Marco Aurélio Ramirez Vinolo (ORCID: https://orcid.org/0000-0003-1335-760X)
- Helison Rafael Pereira do Carmo (ORCID: https://orcid.org/0000-0003-0608-8640)
- Alessandro S. Farias (ORCID: https://orcid.org/0000-0001-6759-1819)
- Daniel Martins‐de‐Souza (ORCID: https://orcid.org/0000-0003-3595-5846)
- Gustavo Gastão Davanzo (ORCID: https://orcid.org/0000-0002-6723-1933)
- Webster Leonardo Guimarães da Costa (ORCID: https://orcid.org/0000-0003-4289-4295)
- Larissa Menezes dos Reis (ORCID: https://orcid.org/0000-0003-1597-0176)
- Douglas C. Wallace
- José Luiz Proença‐Módena (ORCID: https://orcid.org/0000-0002-4996-3153)
- Stéfanie Primon Muraro (ORCID: https://orcid.org/0000-0002-5105-6659)
- Marcelo Rodrigues Berçot (ORCID: https://orcid.org/0000-0003-2803-482X)
- Pedro M. Moraes‐Vieira (ORCID: https://orcid.org/0000-0002-8263-786X)
- Afshin Beheshti (ORCID: https://orcid.org/0000-0003-4643-531X)
- Guilherme Ribeiro (ORCID: https://orcid.org/0000-0002-5564-8619)
- Andrei C. Spósito (ORCID: https://orcid.org/0000-0001-7127-2052)
- Gabriela Fabiano de Souza (ORCID: https://orcid.org/0000-0001-7285-0790)
- Sarah de Oliveira (ORCID: https://orcid.org/0000-0002-9449-9740)
- Ivone B. Oliveira
Institutions
- Broad Institute (US)
- Children's Hospital of Philadelphia (US)
- University of Pittsburgh (US)
- Universidade Estadual de Campinas (UNICAMP) (BR)
- McGowan Institute for Regenerative Medicine (US)
Publication Details
- Journal
- Immunology
- Published
- 2025-04-23
- DOI
- https://doi.org/10.1111/imm.13934
- Citations
- 1
- Primary Topic
- COVID-19 Clinical Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 1.40
Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Universidade Estadual de Campinas
- Fundo de Apoio ao Ensino, à Pesquisa e Extensão, Universidade Estadual de Campinas