Dietary plant sterols accumulate in the brain

Paula J. Jansen; Dieter Lütjohann; Karlygash Abildayeva; Tim Vanmierlo; Torsten Plösch; Jogchum Plat; Klaus von Bergmann; Albert K. Groen; Frans C.S. Ramaekers; Folkert Kuipers; Monique Mulder

doi:10.1016/j.bbalip.2006.03.015

Dietary plant sterols accumulate in the brain

Paula J. Jansen^*, Dieter Lütjohann, Karlygash Abildayeva, Tim Vanmierlo, Torsten Plösch, Jogchum Plat, Klaus von Bergmann, Albert K. Groen, Frans C.S. Ramaekers, Folkert Kuipers, Monique Mulder

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

86 Citations (Scopus)

Abstract

Dietary plant sterols and cholesterol have a comparable chemical structure. It is generally assumed that cholesterol and plant sterols do not cross the blood-brain barrier, but quantitative data are lacking. Here, we report that mice deficient for ATP-binding cassette transporter G5 (Abcg5) or Abcg8, with strongly elevated serum plant sterol levels, display dramatically increased (7- to 16-fold) plant sterol levels in the brain. Apolipoprotein E (ApoE)-deficient mice also displayed elevated serum plant sterol levels, which was however not associated with significant changes in brain plant sterol levels. Abcg5- and Abcg8-deficient mice were found to carry circulating plant sterols predominantly in high-density lipoprotein (HDL)-particles, whereas ApoE-deficient mice accommodated most of their serum plant sterols in very low-density lipoprotein (VLDL)-particles. This suggests an important role for HDL and/or ApoE in the transfer of plant sterols into the brain. Moreover, sitosterol upregulated apoE mRNA and protein levels in astrocytoma, but not in neuroblastoma cells, to a higher extend than cholesterol. In conclusion, dietary plant sterols pass the blood-brain barrier and accumulate in the brain, where they may exert brain cell type-specific effects.

Original language	English
Pages (from-to)	445-453
Number of pages	9
Journal	Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume	1761
Issue number	4
DOIs	https://doi.org/10.1016/j.bbalip.2006.03.015
Publication status	Published - Apr 2006
Externally published	Yes

Bibliographical note

Funding Information:
The authors express their gratitude to Vincent Bloks from the University Medical Center Groningen, The Netherlands, Patrick van Gorp from the University of Maastricht, The Netherlands, Elga de Vries from the VU University Medical Center, The Netherlands and Anja Kerksiek from the University of Bonn, Germany for their excellent technical assistance. This study was supported by a grant from ISAO (grant no. 03516), by the Marie Curie Fellowship Organisation (Quality of Life and Management of Living Resources; Contract number: QLK6-CT-2000-60042; Fellow reference number: QLK6-GH-00-60042-20), by the Dutch Heart Foundation (grant 2004T048 to Torsten Plösch), and by the Hersenstichting Nederland.

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10.1016/j.bbalip.2006.03.015

Cite this

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title = "Dietary plant sterols accumulate in the brain",

abstract = "Dietary plant sterols and cholesterol have a comparable chemical structure. It is generally assumed that cholesterol and plant sterols do not cross the blood-brain barrier, but quantitative data are lacking. Here, we report that mice deficient for ATP-binding cassette transporter G5 (Abcg5) or Abcg8, with strongly elevated serum plant sterol levels, display dramatically increased (7- to 16-fold) plant sterol levels in the brain. Apolipoprotein E (ApoE)-deficient mice also displayed elevated serum plant sterol levels, which was however not associated with significant changes in brain plant sterol levels. Abcg5- and Abcg8-deficient mice were found to carry circulating plant sterols predominantly in high-density lipoprotein (HDL)-particles, whereas ApoE-deficient mice accommodated most of their serum plant sterols in very low-density lipoprotein (VLDL)-particles. This suggests an important role for HDL and/or ApoE in the transfer of plant sterols into the brain. Moreover, sitosterol upregulated apoE mRNA and protein levels in astrocytoma, but not in neuroblastoma cells, to a higher extend than cholesterol. In conclusion, dietary plant sterols pass the blood-brain barrier and accumulate in the brain, where they may exert brain cell type-specific effects.",

author = "Jansen, {Paula J.} and Dieter L{\"u}tjohann and Karlygash Abildayeva and Tim Vanmierlo and Torsten Pl{\"o}sch and Jogchum Plat and {von Bergmann}, Klaus and Groen, {Albert K.} and Ramaekers, {Frans C.S.} and Folkert Kuipers and Monique Mulder",

note = "Funding Information: The authors express their gratitude to Vincent Bloks from the University Medical Center Groningen, The Netherlands, Patrick van Gorp from the University of Maastricht, The Netherlands, Elga de Vries from the VU University Medical Center, The Netherlands and Anja Kerksiek from the University of Bonn, Germany for their excellent technical assistance. This study was supported by a grant from ISAO (grant no. 03516), by the Marie Curie Fellowship Organisation (Quality of Life and Management of Living Resources; Contract number: QLK6-CT-2000-60042; Fellow reference number: QLK6-GH-00-60042-20), by the Dutch Heart Foundation (grant 2004T048 to Torsten Pl{\"o}sch), and by the Hersenstichting Nederland.",

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doi = "10.1016/j.bbalip.2006.03.015",

language = "English",

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pages = "445--453",

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T1 - Dietary plant sterols accumulate in the brain

AU - Jansen, Paula J.

AU - Lütjohann, Dieter

AU - Abildayeva, Karlygash

AU - Vanmierlo, Tim

AU - Plösch, Torsten

AU - Plat, Jogchum

AU - von Bergmann, Klaus

AU - Groen, Albert K.

AU - Ramaekers, Frans C.S.

AU - Kuipers, Folkert

AU - Mulder, Monique

N1 - Funding Information: The authors express their gratitude to Vincent Bloks from the University Medical Center Groningen, The Netherlands, Patrick van Gorp from the University of Maastricht, The Netherlands, Elga de Vries from the VU University Medical Center, The Netherlands and Anja Kerksiek from the University of Bonn, Germany for their excellent technical assistance. This study was supported by a grant from ISAO (grant no. 03516), by the Marie Curie Fellowship Organisation (Quality of Life and Management of Living Resources; Contract number: QLK6-CT-2000-60042; Fellow reference number: QLK6-GH-00-60042-20), by the Dutch Heart Foundation (grant 2004T048 to Torsten Plösch), and by the Hersenstichting Nederland.

PY - 2006/4

Y1 - 2006/4

N2 - Dietary plant sterols and cholesterol have a comparable chemical structure. It is generally assumed that cholesterol and plant sterols do not cross the blood-brain barrier, but quantitative data are lacking. Here, we report that mice deficient for ATP-binding cassette transporter G5 (Abcg5) or Abcg8, with strongly elevated serum plant sterol levels, display dramatically increased (7- to 16-fold) plant sterol levels in the brain. Apolipoprotein E (ApoE)-deficient mice also displayed elevated serum plant sterol levels, which was however not associated with significant changes in brain plant sterol levels. Abcg5- and Abcg8-deficient mice were found to carry circulating plant sterols predominantly in high-density lipoprotein (HDL)-particles, whereas ApoE-deficient mice accommodated most of their serum plant sterols in very low-density lipoprotein (VLDL)-particles. This suggests an important role for HDL and/or ApoE in the transfer of plant sterols into the brain. Moreover, sitosterol upregulated apoE mRNA and protein levels in astrocytoma, but not in neuroblastoma cells, to a higher extend than cholesterol. In conclusion, dietary plant sterols pass the blood-brain barrier and accumulate in the brain, where they may exert brain cell type-specific effects.

AB - Dietary plant sterols and cholesterol have a comparable chemical structure. It is generally assumed that cholesterol and plant sterols do not cross the blood-brain barrier, but quantitative data are lacking. Here, we report that mice deficient for ATP-binding cassette transporter G5 (Abcg5) or Abcg8, with strongly elevated serum plant sterol levels, display dramatically increased (7- to 16-fold) plant sterol levels in the brain. Apolipoprotein E (ApoE)-deficient mice also displayed elevated serum plant sterol levels, which was however not associated with significant changes in brain plant sterol levels. Abcg5- and Abcg8-deficient mice were found to carry circulating plant sterols predominantly in high-density lipoprotein (HDL)-particles, whereas ApoE-deficient mice accommodated most of their serum plant sterols in very low-density lipoprotein (VLDL)-particles. This suggests an important role for HDL and/or ApoE in the transfer of plant sterols into the brain. Moreover, sitosterol upregulated apoE mRNA and protein levels in astrocytoma, but not in neuroblastoma cells, to a higher extend than cholesterol. In conclusion, dietary plant sterols pass the blood-brain barrier and accumulate in the brain, where they may exert brain cell type-specific effects.

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DO - 10.1016/j.bbalip.2006.03.015

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SN - 1388-1981

VL - 1761

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EP - 453

JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

IS - 4

ER -

Dietary plant sterols accumulate in the brain

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