Enhanced production of nitric oxide, reactive oxygen species, and pro-inflammatory cytokines in very long chain saturated fatty acid-accumulated macrophages
Open accessAbstract
Background: Deterioration of peroxisomal β-oxidation activity causes an accumulation of very long chain saturated fatty acids (VLCSFA) in various organs. We have recently reported that the levels of VLCSFA in the plasma and/or membranes of blood cells were significantly higher in patients with metabolic syndrome and in patients with coronary artery disease than the controls. The aim of the present study is to investigate the effect of VLCSFA accumulation on inflammatory and oxidative responses in VLCSFA-accumulated macrophages derived from X-linked adrenoleukodystrophy (X-ALD) protein (ALDP)-deficient mice. Results: Elevated levels of VLCSFA were confirmed in macrophages from ALDP-deficient mice. The levels of nitric oxide (NO) production stimulated by lipopolysaccharide (LPS) and interferon-γ (IFN-γ), intracellular reactive oxygen species (ROS), and pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interluekin-6 (IL-6), and interleukin-12p70 (IL-12p70), were significantly higher in macrophages from ALDP-deficient mice than in those from wild-type mice. The inducible NO synthase (iNOS) mRNA expression also showed an increase in macrophages from ALDP-deficient mice. Conclusion: These results suggested that VLCSFA accumulation in macrophages may contribute to the pathogenesis of inflammatory diseases through the enhancement of inflammatory and oxidative responses.
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Abcd1-deficient mouse peritoneal macrophages show a two-fold increase in the C26:0/C22:0 ratio compared with wild-type.
“Compared with wild-type levels, we found a two-fold increase in the ratio C26∶0/C22∶0 (Fig. 3A).”
From Abcd2 Is a Strong Modifier of the Metabolic Impairments in Peritoneal Macrophages of Abcd1-Deficient Mice (2014) · cites this paper as [27]
The Results section, “Quantification of C26:0” (page unavailable), reports that the C26:0/C22:0 ratio in macrophages from ALDP-deficient mice was significantly higher than in wild-type mice. Our copy does not give a numerical ratio or establish the claimed two-fold increase. (LLM, conf=0.86)
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Weber, F. D., Wiesinger, C., Forss-Petter, S., Regelsberger, G., Einwich, A., Weber, W. H. A., Kohler, W., Stockinger, H., & Berger, J. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddt645 · Cited by 63 · see citing works
Muneer, Z., Wiesinger, C., Voigtländer, T., Werner, H. B., Berger, J., & Forss-Petter, S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0108655 · Cited by 33 · see citing works
- Authors
- Yanagisawa, N., Shimada, K., Miyazaki, T., Kume, A., Kitamura, Y., Sumiyoshi, K., Kiyanagi, T., Iesaki, T., Inoue, N., & Daida, H.
- Affiliations
- Juntendo University (JP)
- Morinaga Milk Industry Co., Ltd. (Japan) (JP)
- Corresponding author
- Shimada, Kazunori
- Venue
- Lipids in Health and Disease
- Published
- 2008-11-28
- Volume
- 7
- Issue
- 1
- Pages
- 48-48
- ISSN
- 1476-511X (ISSN-L)
- PMC
- PMC2613382
- OpenAlex
- W2113312309
- Cited by
- 29
- References
- 1
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 1 · 2014: 3 · 2013: 3 · 2012: 1
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Lipids in Health and Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- Morinaga Milk Industry
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- very long-chain saturated fatty acids, macrophages, nitric oxide, reactive oxygen species, inflammatory cytokines, X-linked adrenoleukodystrophy, peroxisomal beta-oxidation, inducible nitric oxide synthase, inflammation, oxidative stress, metabolic syndrome, coronary artery disease
- MeSH terms
- Animals, Cells, Cultured, Fatty Acids, Interferon-gamma, Lipopolysaccharides, Macrophages, Male, Mice, Mutant Strains, Nitric Oxide, Tumor Necrosis Factor-alpha, Interleukin-6, Cytokines, Reactive Oxygen Species, Interleukin-12, Mice, Nitric Oxide Synthase Type II
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