Dietary plant sterols accumulate in the brain

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

doi:10.1016/j.bbalip.2006.03.015

Cited by 87 publications

(91 citation statements)

References 35 publications

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“…Because the onset of motor dysfunction in untreated LXR␤ Ϫ/Ϫ mice begins at Ϸ6 months of age, it appears that ␤-sitosterol accentuates and accelerates the degeneration that occurs in LXR␤ Ϫ/Ϫ mice. Elevated levels of plant sterols occur in the brains of ABCG5 Ϫ/Ϫ or ABCG8 Ϫ/Ϫ mice (17). Although high levels of plant sterol disrupt cholesterol metabolism in extra-cerebral tissues, accumulation of ␤-sitosterol has no detectable effect on overall brain cholesterol metabolism (17).…”

Section: Discussionmentioning

confidence: 99%

“…Elevated levels of plant sterols occur in the brains of ABCG5 Ϫ/Ϫ or ABCG8 Ϫ/Ϫ mice (17). Although high levels of plant sterol disrupt cholesterol metabolism in extra-cerebral tissues, accumulation of ␤-sitosterol has no detectable effect on overall brain cholesterol metabolism (17). Our study suggests that when LXR␤ signaling is abnormal, ingestion of ␤-sitosterol can lead to neuronal damage in both spinal cord and substantia nigra, thus ␤-sitosterol could be a common etiological agent in both PDC and ALS.…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in ABCG5 and ABCG8 have been found in sitosterolemic patients, but those subjects do not develop motor neuron disease (11)(12)(13)(14)(15)(16). Similarly, mice in which ABCG5 and ABCG8 have been inactivated develop sitosterolemia but not motor neuron disease (17).…”

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confidence: 99%

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Liver X receptor β (LXRβ): A link between β-sitosterol and amyotrophic lateral sclerosis–Parkinson's dementia

Kim¹,

Fan²,

Gabbi³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

122

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Administration of ␤-sitosterol (42 mg/kg per day) for 3 weeks to 8-month-old male LXR␤ ؊/؊ mice resulted in the death of motor neurons in the lumbar region of the spinal cord and loss of tyrosine hydroxylase-positive dopaminergic neurons in the substantia nigra. In mice at 5 months of age, ␤-sitosterol had no observed toxicity but at 16 months of age, it caused severe paralysis and symptoms typical of dopaminergic dysfunction in LXR␤ ؊/؊ mice. WT mice were not affected by these doses of ␤-sitosterol. In 5-month-old mice, levels of the intestinal transporters, ABCG5/8 and Niemann-Pick C1 Like 1, were not affected by loss of liver X receptor (LXR) ␤ and/or treatment with ␤-sitosterol nor were there changes in plasma levels of cholesterol or ␤-sitosterol. In 8-monthold LXR␤ ؊/؊ mice there was activation of microglia in the substantia nigra pars reticulata and aggregates of ubiquitin and TDP-43 in the cytoplasm of large motor neurons in the lumbar spinal cord. Brain cholesterol concentrations were higher in LXR␤ ؊/؊ than in their WT counterparts, and treatment with ␤-sitosterol reduced brain cholesterol in both WT and LXR␤ ؊/؊ mice. In LXR␤ ؊/؊ mice but not in WT mice levels of 24-hydrocholesterol were increased upon ␤-sitosterol treatment. These data indicate that multiple mechanisms are involved in the sensitivity of LXR␤ ؊/؊ mice to ␤-sitosterol. These include activation of microglia, accumulation of protein aggregates in the cytoplasm of large motor neurons, and depletion of brain cholesterol.central nervous system ͉ cholesterol ͉ microglia ͉ neurodegenerative disease ͉ nuclear receptor

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Liver X receptor β (LXRβ): A link between β-sitosterol and amyotrophic lateral sclerosis–Parkinson's dementia

Kim¹,

Fan²,

Gabbi³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

122

View full text Add to dashboard Cite

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“…Brain cholesterol homeostasis and phytosterol intake are closely interlinked and diets with specific composition of phytosterols are possibly important in the maintenance of liver, brain and oxysterol metabolism [97][98][99][100][101][102][103][104][105][106]. Phytosterols such as campesterol and stigmasterol inhibit intestinal cholesterol absorption and beta-sitosterol and stigmasterol act on the liver to reduce cholesterol levels (Figure 2, ref [97,99,101]).…”

Section: Phytosterols and Cholesterol Homeostasismentioning

confidence: 99%

High Fibre Diets and Alzheimer’s Disease

Martins¹,

Fernando²

2014

FNS

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“…Pelo fato de serem substâncias com comprovado efeito biológico, é possível que a interação entre CLA e fitosteróis melhore e/ou potencialize seus efeitos, aumentando a absorção dos fitosteróis pelo organismo, atuando na composição corporal, regulando os níveis de lipoproteínas séricas e reduzindo a resistência à insulina (COULTATE, 2002;NTANIOS et al, 2003;JANSEN et al, 2006). O objetivo deste trabalho foi, portanto, avaliar as possíveis alterações causadas pela ingestão de CLA e de fitosteróis no ganho de peso, na glicemia e no perfil lipídico de camundongos alimentados com dieta hiperlipídica.…”

Section: Introductionunclassified

Redução do peso e da glicemia resultante da suplementação de ácido linoleico conjugado e fitosteróis à dieta hiperlipídica de camundongos

2012

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Redução do peso e da glicemia resultante da suplementação de ácido linoleico conjugado e fitosteróis à dieta hiperlipídica de camundongosWeight and blood glucose reduction resulting from conjugated linoleic acid and phytosterols supplementation on hiperlipidic diets of mice INTRODUÇÃOA informação de que a obesidade é um problema de saúde pública já se tornou senso comum. Entre as principais consequências dessa doença, que atinge milhões de pessoas no mundo, tem-se o desenvolvimento de dislipidemia, doenças cardiovasculares, osteoartrite, hérnias, diabetes, entre outros (COSTA, 2005). Diante da gravidade do quadro, inúmeras pesquisas têm apontado possíveis medicamentos, compostos e alimentos capazes de reduzir tanto a incidência quanto a prevalência da obesidade.Entre os compostos oriundos dos alimentos, o ácido linoleico conjugado (CLA) vem recebendo destaque devido a sua ação reguladora do balanço energético e da composição corporal, reduzindo o ganho de peso e de massa gorda, além de aumentar massa magra (MOURÃO et al., 2005). O CLA é um grupo de ácidos graxos isômeros geométricos e de posição do ácido linoleico (C18:2 9c,12c n-6), sendo os isômeros 9c,11t e 10t,12c os mais estudados. A gordura e o leite de animais ruminantes são importantes fontes alimentares desse composto, o qual pode também ser produzido quimicamente a partir do ácido linoleico

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Dietary plant sterols accumulate in the brain

Cited by 87 publications

References 35 publications

Liver X receptor β (LXRβ): A link between β-sitosterol and amyotrophic lateral sclerosis–Parkinson's dementia

Liver X receptor β (LXRβ): A link between β-sitosterol and amyotrophic lateral sclerosis–Parkinson's dementia

High Fibre Diets and Alzheimer’s Disease

Redução do peso e da glicemia resultante da suplementação de ácido linoleico conjugado e fitosteróis à dieta hiperlipídica de camundongos

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