Altered adipose tissue macrophage populations in people with HIV on integrase inhibitor-containing antiretroviral therapy.
Journal
AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219
Informations de publication
Date de publication:
01 09 2022
01 09 2022
Historique:
pubmed:
19
7
2022
medline:
20
8
2022
entrez:
18
7
2022
Statut:
ppublish
Résumé
Antiretroviral therapy (ART) extends the life of people with HIV (PWH), but these individuals are at increased risk for obesity, dyslipidemia, diabetes, and cardiovascular disease. These comorbidities may be a consequence of HIV-related chronic inflammation and/or adverse effects of ART on tissue regulatory adipose tissue macrophages (ATMs). We sought to determine the effects of HIV/ART on metabolically beneficial ATM populations and functions. We examined subcutaneous ATMs from PWH on integrase inhibitor-containing ART ( n = 5) and uninfected persons ( n = 9). We complemented these studies with ex vivo and in vitro analyses of peripheral blood mononuclear cell (PBMC) and murine macrophage lipid metabolism and fatty acid oxidation gene expression. ATM populations were examined by flow cytometry. Macrophage lipid metabolism and fatty acid oxidation gene expression were examined by Seahorse assay and quantitative PCR. Adipose tissue from PWH had reduced populations of metabolically activated CD9 + ATMs compared to that of uninfected controls ( P < 0.001). PBMCs of PWH had lower fatty acid metabolism compared to those of uninfected controls ( P < 0.01). Analysis of murine macrophages revealed that dolutegravir reduced lipid metabolism ( P < 0.001) and increased expression of the fatty acid beta-oxidation enzyme enoyl-CoA hydratase, short chain 1 ( P < 0.05). We report the loss of metabolically beneficial ATM populations in PWH on ART, altered fatty acid metabolism of blood immune cells, and evidence that dolutegravir alters macrophage fatty acid metabolism. Future studies should examine direct or indirect effects and mechanisms of dolutegravir, and other integrase inhibitors and ART classes, on fatty acid beta-oxidation.
Identifiants
pubmed: 35848549
doi: 10.1097/QAD.0000000000003278
pii: 00002030-202209010-00002
pmc: PMC9391287
mid: NIHMS1812295
doi:
Substances chimiques
Fatty Acids
0
HIV Integrase Inhibitors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1493-1500Subventions
Organisme : NIDDK NIH HHS
ID : K08 DK116668
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI045008
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK019525
Pays : United States
Organisme : NIMH NIH HHS
ID : P30 MH097488
Pays : United States
Informations de copyright
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.
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