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Cited by 18Cholesterol and Lipid MetabolismImmune cells in cancerAtherosclerosis and Cardiovascular Diseases

Accumulation of cholesterol suppresses oxidative phosphorylation and altered responses to inflammatory stimuli of macrophages

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Chiu, Yi-Chou, Chu, Pei-Wen, Lin, Hua-Ching, Chen, Shau-Kwaun·2021·Biochemistry and Biophysics Reports
DOI 10.1016/j.bbrep.2021.101166PMC PMC8579117
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Abstract

Hypercholesterolemia induces intracellular accumulation of cholesterol in macrophages and other immune cells, causing immunological dysfunctions. On cellular levels, cholesterol enrichment might lead to mitochondrial metabolic reprogramming and change macrophage functions. Additionally, as cholesterol is permeable to the plasma membrane and might integrate into the membranous organelles, such as endoplasmic reticulum or mitochondria, cholesterol enrichment might change the functions or properties of these organelles, and ultimately alters the cellular functions. In this study, we investigate the mitochondrial alterations and intracellular oxidative stress induced by accumulation of cholesterol in the macrophages, and the possible immunological impacts caused by these alterations. Macrophage cells RAW264.7 were treated with cholesterol to induce intracellular accumulation of cholesterol, which further triggered the reduced production of reactive oxygen/nitrogen species, as well as decrease of oxidative phosphorylation. Basal respiration rate, ATP production and non-mitochondrial oxygen consumption are all suppressed. In contrast, glycolysis remained unaltered in this cholesterol-enriched condition. Previous studies demonstrated that metabolic profiles are associated with macrophage polarization. We further verified whether this metabolic reprogramming influences the macrophage responses to pro-inflammatory or anti-inflammatory stimuli. Our results showed the changes of transcriptional regulations in both pro-inflammatory and anti-inflammatory genes, but not specific toward M1 or M2 polarization. Collectively, the accumulation of cholesterol induced mitochondrial metabolic reprogramming and suppressed the production of oxidative stress, and induced the alterations of macrophage functions.

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Authors
Chiu, Y.-C., Chu, P.-W., Lin, H.-C., & Chen, S.-K.
Affiliations
  • Cheng Hsin General Hospital (TW)
  • National Chengchi University (TW)
  • Ming Chuan University (TW)
Corresponding author
Chen, Shau-Kwaun
ORCID
Venue
Biochemistry and Biophysics Reports
Publisher
Elsevier BV
Published
2021-12
Volume
28
Pages
101166
ISSN
2405-5808 (ISSN-L)
DOI
10.1016/j.bbrep.2021.101166
PMC
PMC8579117
OpenAlex
W3209157631
Cited by
18
References
2
Citations by year
2026: 5 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 3
FWCI
2.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Biochemistry and Biophysics Reports (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Cheng Hsin General Hospital (CHGH108)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Keywords
intracellular cholesterol accumulation, hypercholesterolemia, macrophages, oxidative phosphorylation, mitochondrial metabolic reprogramming, oxidative stress, reactive oxygen species, glycolysis, macrophage polarization, immunometabolism, RAW 264.7 macrophages

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