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Int J Mol Sci. 2021 Dec 08;22(24). doi: 10.3390/ijms222413207.

Plant Sterol-Poor Diet Is Associated with Pro-Inflammatory Lipid Mediators in the Murine Brain.

International journal of molecular sciences

Madlen Reinicke, Judith Leyh, Silke Zimmermann, Soroth Chey, Ilijana Begcevic Brkovic, Christin Wassermann, Julia Landmann, Dieter Lütjohann, Berend Isermann, Ingo Bechmann, Uta Ceglarek

Affiliations

  1. Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, Liebigstr. 27, 04103 Leipzig, Germany.
  2. Institute of Anatomy, Leipzig University, Liebigstr. 13, 04103 Leipzig, Germany.
  3. Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.

PMID: 34948003 DOI: 10.3390/ijms222413207

Abstract

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 β-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 β-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.

Keywords: COX; brain; inflammation; microglia; plant sterols

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