On the regulatory role of side-chain hydroxylated oxysterols in the brain. Lessons from CYP27A1 transgenic and Cyp27a1(−/−) mice
Open accessAbstract
The two oxysterols, 27-hydroxycholesterol (27OH) and 24S-hydroxycholesterol (24OH), are both inhibitors of cholesterol synthesis and activators of the liver X receptor (LXR) in vitro. Their role as physiological regulators under in vivo conditions is controversial, however. In the present work, we utilized a previously described mouse model with overexpressed human sterol 27-hydroxylase (CYP27A1). The levels of 27OH were increased about 12-fold in the brain. The brain levels of HMG-CoA reductase mRNA and HMG-CoA synthase mRNA levels were increased. In accordance with increased cholesterol synthesis, most of the cholesterol precursors were also increased. The level of 24OH, the dominating oxysterol in the brain, was decreased by about 25%, most probably due to increased metabolism by CYP27A1. The LXR target genes were unaffected or slightly changed in a direction opposite to that expected for LXR activation. In the brain of Cyp27(-/-) mice, cholesterol synthesis was slightly increased, with increased levels of cholesterol precursors but normal mRNA levels of HMG-CoA reductase and HMG-CoA synthase. The mRNA levels corresponding to LXR target genes were not affected. The results are consistent with the possibility that both 24OH and 27OH are physiological suppressors of cholesterol synthesis in the brain. The results do not support the contention that 27OH is a general activator of LXR target genes in this organ.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
27-hydroxycholesterol exerts regulatory effects on brain cholesterol homeostasis.
“Inclusion of 27-hydroxycholesterol is warranted based on studies in other models suggesting that this oxysterol exerts regulatory effects on brain cholesterol homeostasis (Ali et al., 2013; Zhang et al., 2015).”
From Suppression of brain cholesterol synthesis in male Mecp2-deficient mice is age dependent and not accompanied by a concurrent change in the rate of fatty acid synthesis (2017) · cites this paper as Ali et al., 2013
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 33 · Cited by 54
Research works printed but not linked: 2
- Janowski , B. A. , M. J. Grogan , S. A. Jones , G. B. Wisely , S. A. Kliewer , E. J. Corey , and D. J. Mangelsdorf . 1999 . Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta. Proc. Natl. Acad. Sci. USA . 96 : 266 -271 .
- Lütjohann , D. , O. Breuer , G. Ahlborg , I. Nennesmo , A. Siden , U. Diczfalusy , and I. Björkhem . 1996 . Cholesterol homeostasis in hu- man brain: evidence for an age-dependent fl ux of 24S-hydroxyc- holesterol from the brain into the circulation. Proc. Natl. Acad. Sci. USA . 93 : 9799 -9804 .
- Authors
- Ali, Z., Heverin, M., Olin, M., Acimovic, J., Lövgren-Sandblom, A., Shafaati, M., Båvner, A., Meiner, V., Leitersdorf, E., & Björkhem, I.
- Affiliations
- Karolinska Institutet (SE)
- Hebrew University of Jerusalem (IL)
- Corresponding author
- Björkhem, Ingemar
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 54
- Issue
- 4
- Pages
- 1033-1043
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC3605980
- OpenAlex
- W2066248739
- Cited by
- 54
- References
- 33
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 9 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 1 · 2016: 7 · 2015: 3 · 2014: 7 · 2013: 4
- FWCI
- 6.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Hjärnfonden
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- oxysterols, 27-hydroxycholesterol, 24S-hydroxycholesterol, CYP27A1, liver X receptor, cholesterol biosynthesis, HMG-CoA reductase, HMG-CoA synthase, brain, transgenic mice, cholesterol precursors
- MeSH terms
- Liver X Receptors, Animals, Brain, Cholesterol, Female, Humans, Hydroxycholesterols, Hydroxymethylglutaryl-CoA Synthase, Male, Mice, Transgenic, Mice, Knockout, Mice, Cholestanetriol 26-Monooxygenase, Orphan Nuclear Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
