Plant sterols (PSs) cannot be synthesized in mammals and are exclusively diet-derived.
PSs cross the blood-brain barrier and may have anti-neuroinflammatory effects. Obesity is linked
to lower intestinal uptake and blood levels of PSs, but its effects in terms of neuroinflammation—if
any—remain unknown. We investigated the effect of high-fat diet-induced obesity on PSs in the
brain and the effects of the PSs campesterol and -sitosterol on in vitro microglia activation. Sterols
(cholesterol, precursors, PSs) and polyunsaturated fatty acid-derived lipid mediators were measured
in the food, blood, liver and brain of C57BL/6J mice. Under a PSs-poor high-fat diet, PSs levels
decreased in the blood, liver and brain (>50%). This effect was reversible after 2 weeks upon changing
back to a chow diet. Inflammatory thromboxane B2 and prostaglandin D2 were inversely correlated
to campesterol and -sitosterol levels in all brain regions. PSs content was determined post mortem in
human cortex samples as well. In vitro, PSs accumulate in lipid rafts isolated from SIM-A9 microglia
cell membranes. In summary, PSs levels in the blood, liver and brain were associated directly with
PSs food content and inversely with BMI. PSs dampen pro-inflammatory lipid mediators in the
brain. The identification of PSs in the human cortex in comparable concentration ranges implies the
relevance of our findings for humans.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89055 |
| Date | 16 January 2024 |
| Creators | Reinicke, Madlen, Leyh, Judith, Zimmermann, Silke, Chey, Soroth, Begcevic Brkovic, Ilijana, Wassermann, Christin, Landmann, Julia, Lütjohann, Dieter, Isermann, Berend, Bechmann, Ingo, Ceglarek, Uta |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 13207 |
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