Exogenous Addition of 25‐Hydroxycholesterol Reduces Level of Very Long‐Chain Fatty Acids in X‐Linked Adrenoleukodystrophy
Open accessAbstract
X‐Linked adrenoleukodystrophy (X‐ALD) is a severe metabolic disorder characterized by the accumulation of very long‐chain fatty acids (VLCFAs). Recently, we demonstrated that levels of 25‐hydroxycholesterol (25‐HC) and cholesterol 25‐hydroxylase (CH25H) were found to be elevated in X‐ALD. Herein, we report that the exogenous addition of 25‐HC significantly reduces C26:0 levels in X‐ALD patient‐derived fibroblasts and oligodendrocytes differentiated from induced pluripotent stem cells (iPSCs) derived from X‐ALD patients. Moreover, 25‐HC treatment was found to down‐regulate the expression of ELOVL1, a key enzyme for the synthesis of C26. In addition, activation of liver X receptor (LXR), a molecular target of endogenous 25‐HC, also reduced C26:0 level. The reduction of C26:0 levels by 25‐HC treatment might result, at least partially, from the decrease of ELOVL1 expression as well as the activation of LXR. Our findings could provide a better understanding of the role of 25‐HC in X‐ALD and useful information to find therapeutic agents to treat X‐ALD.
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25-hydroxycholesterol represses ELOVL1 mRNA levels.
“Conversely, 25-HC repressed ELOVL1 mRNA levels (Fig. 5c), confirming a previous observation in human fibroblasts44.”
From Peroxisomal very long-chain fatty acid transport is targeted by herpesviruses and the antiviral host response (2022) · cites this paper as [44]
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Weinhofer, I., Buda, A., Kunze, M., Palfi, Z., Traunfellner, M., Hesse, S., Villoria-Gonzalez, A., Hofmann, J., Hametner, S., Regelsberger, G., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03867-y · Cited by 20 · see citing works
- Authors
- Jang, J., Lee, J. W., Song, J., Kim, D., & Min, K. H.
- Affiliations
- Yonsei University (KR)
- Chung-Ang University (KR)
- Corresponding author
- Jang, Jiho
- Min, Kyung Hoon
- Venue
- ChemistryOpen
- Publisher
- Wiley
- Published
- 2019-02
- Volume
- 8
- Issue
- 2
- Pages
- 188-191
- ISSN
- 2191-1363 (ISSN-L)
- PMC
- PMC6369660
- OpenAlex
- W2912523205
- Cited by
- 6
- References
- 6
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 1 · 2020: 1 · 2019: 2
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- ChemistryOpen (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Funders
- Advanced Research Center Program (2015R1 A5 A1008958)
- Bio & Medical Technology Development Program of the National Research Foundation (NRF-2018R1D1 A1B07046207)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- X-linked adrenoleukodystrophy, 25-hydroxycholesterol, very long chain fatty acids, cholesterol 25-hydroxylase, ELOVL1, liver X receptor, oligodendrocytes, induced pluripotent stem cells, fibroblasts, therapeutic target
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