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Probucol suppresses enterocytic accumulation of amyloid-β induced by saturated fat and cholesterol feeding.
Lipids 2012; 47(1):27-34L

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.

Authors+Show Affiliations

School of Public Health, Curtin University of Technology, GPO Box U1987, Perth, WA 6845, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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 -