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Obesity‐Induced Metabolic Priming Exacerbates SARS ‐ CoV ‐2 Inflammation
Author(s) -
Davanzo Gustavo Gastão,
Castelucci Bianca Gazieri,
Souza Gabriela Fabiano,
Muraro Stéfanie Primon,
Menezes dos Reis Larissa,
Oliveira Isabella Bonilha,
Fachi José Luís,
VirgiliodaSilva João Victor,
Berçot Marcelo Rodrigues,
Fernandes Mariane Font,
Oliveira Sarah,
Araujo Nathalia Vitoria Pereira,
Ribeiro Guilherme,
Castro Gisele,
Costa Webster Leonardo Guimarães,
Santoro Adriana Leandra,
RodriguesLuiz Gabriela Flavia,
Carmo Helison Rafael P.,
Breder Ikaro,
Mori Marcelo A.,
Farias Alessandro S.,
MartinsdeSouza Daniel,
Guarnieri Joseph W.,
Wallace Douglas C.,
Vinolo Marco Aurélio Ramirez,
ProençaMódena José Luiz,
Beheshti Afshin,
Sposito Andrei C.,
MoraesVieira Pedro M.
Publication year - 2025
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13934
Subject(s) - inflammation , lipolysis , downregulation and upregulation , priming (agriculture) , immunology , obesity , monocyte , immune system , mitochondrion , biology , endocrinology , chemistry , adipose tissue , biochemistry , gene , botany , germination
ABSTRACT 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.