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Probucol suppresses enterocytic accumulation of amyloid-β induced by saturated fat and cholesterol feeding.

Abstract

Amyloid-β (Aβ) is secreted from lipogenic organs such as intestine and liver as an apolipoprotein of nascent triacylglycerol rich lipoproteins. Chronically elevated plasma Aβ may compromise cerebrovascular integrity and exacerbate amyloidosis--a hallmark feature of Alzheimer's disease (AD). Probucol is a hypocholesterolemic agent that reduces amyloid burden in transgenic amyloid mice, but the mechanisms for this effect are presently unclear. In this study, the effect of Probucol on intestinal lipoprotein-Aβ homeostasis was explored. Wild-type mice were fed a control low-fat diet and enterocytic Aβ was stimulated by high-fat (HF) diet enriched in 10% (w/w) saturated fat and 1% (w/w) cholesterol for the duration of 1 month. Mice treated with Probucol had the drug incorporated into the chow at 1% (w/w). Quantitative immunofluorescence was utilised to determine intestinal apolipoprotein B (apo B) and Aβ abundance. We found apo B in both the perinuclear region of the enterocytes and the lacteals in all groups. However, HF feeding and Probucol treatment increased secretion of apo B into the lacteals without any change in net villi abundance. On the other hand, HF-induced enterocytic perinuclear Aβ was significantly attenuated by Probucol. No significant changes in Aβ were observed within the lacteals. The findings of this study support the notion that Probucol suppresses dietary fat induced stimulation of Aβ biosynthesis and attenuate availability of apo B lipoprotein-Aβ for secretion.

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  • Authors+Show Affiliations

    ,

    School of Public Health, Curtin University of Technology, GPO Box U1987, Perth, WA 6845, Australia.

    , , ,

    Source

    Lipids 47:1 2012 Jan pg 27-34

    MeSH

    Alzheimer Disease
    Amyloid beta-Peptides
    Amyloidosis
    Animals
    Anticholesteremic Agents
    Apolipoproteins B
    Cholesterol
    Diet, Atherogenic
    Diet, Fat-Restricted
    Dietary Fats
    Enterocytes
    Female
    Fluorescent Antibody Technique
    Intestine, Small
    Mice
    Mice, Inbred C57BL
    Probucol
    Triglycerides

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21805327

    Citation

    Pallebage-Gamarallage, Menuka M., et al. "Probucol Suppresses Enterocytic Accumulation of Amyloid-β Induced By Saturated Fat and Cholesterol Feeding." Lipids, vol. 47, no. 1, 2012, pp. 27-34.
    Pallebage-Gamarallage MM, Galloway S, Takechi R, et al. Probucol suppresses enterocytic accumulation of amyloid-β induced by saturated fat and cholesterol feeding. Lipids. 2012;47(1):27-34.
    Pallebage-Gamarallage, M. M., Galloway, S., Takechi, R., Dhaliwal, S., & Mamo, J. C. (2012). Probucol suppresses enterocytic accumulation of amyloid-β induced by saturated fat and cholesterol feeding. Lipids, 47(1), pp. 27-34. doi:10.1007/s11745-011-3595-4.
    Pallebage-Gamarallage MM, et al. Probucol Suppresses Enterocytic Accumulation of Amyloid-β Induced By Saturated Fat and Cholesterol Feeding. Lipids. 2012;47(1):27-34. PubMed PMID: 21805327.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Probucol suppresses enterocytic accumulation of amyloid-β induced by saturated fat and cholesterol feeding. AU - Pallebage-Gamarallage,Menuka M, AU - Galloway,Susan, AU - Takechi,Ryusuke, AU - Dhaliwal,Satvinder, AU - Mamo,John C L, Y1 - 2011/07/31/ PY - 2011/02/07/received PY - 2011/07/07/accepted PY - 2011/8/2/entrez PY - 2011/8/2/pubmed PY - 2012/6/7/medline SP - 27 EP - 34 JF - Lipids JO - Lipids VL - 47 IS - 1 N2 - Amyloid-β (Aβ) is secreted from lipogenic organs such as intestine and liver as an apolipoprotein of nascent triacylglycerol rich lipoproteins. Chronically elevated plasma Aβ may compromise cerebrovascular integrity and exacerbate amyloidosis--a hallmark feature of Alzheimer's disease (AD). Probucol is a hypocholesterolemic agent that reduces amyloid burden in transgenic amyloid mice, but the mechanisms for this effect are presently unclear. In this study, the effect of Probucol on intestinal lipoprotein-Aβ homeostasis was explored. Wild-type mice were fed a control low-fat diet and enterocytic Aβ was stimulated by high-fat (HF) diet enriched in 10% (w/w) saturated fat and 1% (w/w) cholesterol for the duration of 1 month. Mice treated with Probucol had the drug incorporated into the chow at 1% (w/w). Quantitative immunofluorescence was utilised to determine intestinal apolipoprotein B (apo B) and Aβ abundance. We found apo B in both the perinuclear region of the enterocytes and the lacteals in all groups. However, HF feeding and Probucol treatment increased secretion of apo B into the lacteals without any change in net villi abundance. On the other hand, HF-induced enterocytic perinuclear Aβ was significantly attenuated by Probucol. No significant changes in Aβ were observed within the lacteals. The findings of this study support the notion that Probucol suppresses dietary fat induced stimulation of Aβ biosynthesis and attenuate availability of apo B lipoprotein-Aβ for secretion. SN - 1558-9307 UR - https://www.unboundmedicine.com/medline/citation/21805327/Probucol_suppresses_enterocytic_accumulation_of_amyloid_β_induced_by_saturated_fat_and_cholesterol_feeding_ L2 - https://link.springer.com/article/10.1007/s11745-011-3595-4 DB - PRIME DP - Unbound Medicine ER -