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The effect of exogenous cholesterol and lipid-modulating agents on enterocytic amyloid-beta abundance.
Br J Nutr 2009; 101(3):340-7BJ

Abstract

Dietary cholesterol may influence Alzheimer's disease risk, because it regulates the synthesis of amyloid-beta. It was recently demonstrated in enterocytes of wild-type mice that intracellular amyloid-beta expression is enhanced in response to a high-fat diet made up of SFA and cholesterol. Intestinally derived amyloid-beta may be associated with postprandial lipoproteins in response to dietary fats and could be a key regulator in chylomicron metabolism. The present study was designed to investigate the role of cholesterol in modulating amyloid-beta abundance in enterocytes. Wild-type mice were fed a low-fat diet supplemented with 2 % (w/w) cholesterol. The effects of cholesterol absorption inhibition and cholesterol biosynthesis inhibition utilising ezetimibe and atorvastatin, respectively, were also studied. Quantitative immunohistochemistry was utilised to determine enterocytic amyloid-beta homeostasis. We found that enterocytic amyloid-beta concentration was significantly attenuated in mice fed the 2 % (w/w) cholesterol diet. However, blocking cholesterol absorption reversed the cholesterol-feeding effect. Consistent with a suppressive effect of cholesterol on enterocytic amyloid-beta abundance, atorvastatin, an inhibitor of cholesterol biosynthesis, enhanced amyloid-beta. However, providing exogenous cholesterol abolished the atorvastatin-induced effect. In contrast to the suppression of enterocytic amyloid-beta by dietary cholesterol, mice fed a diet enriched in SFA had markedly greater abundance. Collectively, the findings suggest that exogenous and endogenous cholesterol reduce amyloid-beta concentration in enterocytes by suppressing production, or enhancing secretion associated with postprandial lipoproteins. Intestinally derived amyloid-beta will contribute to the pool of plasma protein and may influence cerebral amyloid homeostasis by altering the bi-directional transfer across the blood-brain barrier.

Authors+Show Affiliations

School of Biomedical Sciences, Curtin University of Technology, Perth, WA, Australia.No affiliation info availableNo 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

18631412

Citation

Pallebage-Gamarallage, Menuka M., et al. "The Effect of Exogenous Cholesterol and Lipid-modulating Agents On Enterocytic Amyloid-beta Abundance." The British Journal of Nutrition, vol. 101, no. 3, 2009, pp. 340-7.
Pallebage-Gamarallage MM, Galloway S, Johnsen R, et al. The effect of exogenous cholesterol and lipid-modulating agents on enterocytic amyloid-beta abundance. Br J Nutr. 2009;101(3):340-7.
Pallebage-Gamarallage, M. M., Galloway, S., Johnsen, R., Jian, L., Dhaliwal, S., & Mamo, J. C. (2009). The effect of exogenous cholesterol and lipid-modulating agents on enterocytic amyloid-beta abundance. The British Journal of Nutrition, 101(3), pp. 340-7. doi:10.1017/S0007114508012269.
Pallebage-Gamarallage MM, et al. The Effect of Exogenous Cholesterol and Lipid-modulating Agents On Enterocytic Amyloid-beta Abundance. Br J Nutr. 2009;101(3):340-7. PubMed PMID: 18631412.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of exogenous cholesterol and lipid-modulating agents on enterocytic amyloid-beta abundance. AU - Pallebage-Gamarallage,Menuka M, AU - Galloway,Susan, AU - Johnsen,Russell, AU - Jian,Le, AU - Dhaliwal,Satvinder, AU - Mamo,John C L, Y1 - 2008/07/17/ PY - 2008/7/18/pubmed PY - 2009/6/12/medline PY - 2008/7/18/entrez SP - 340 EP - 7 JF - The British journal of nutrition JO - Br. J. Nutr. VL - 101 IS - 3 N2 - Dietary cholesterol may influence Alzheimer's disease risk, because it regulates the synthesis of amyloid-beta. It was recently demonstrated in enterocytes of wild-type mice that intracellular amyloid-beta expression is enhanced in response to a high-fat diet made up of SFA and cholesterol. Intestinally derived amyloid-beta may be associated with postprandial lipoproteins in response to dietary fats and could be a key regulator in chylomicron metabolism. The present study was designed to investigate the role of cholesterol in modulating amyloid-beta abundance in enterocytes. Wild-type mice were fed a low-fat diet supplemented with 2 % (w/w) cholesterol. The effects of cholesterol absorption inhibition and cholesterol biosynthesis inhibition utilising ezetimibe and atorvastatin, respectively, were also studied. Quantitative immunohistochemistry was utilised to determine enterocytic amyloid-beta homeostasis. We found that enterocytic amyloid-beta concentration was significantly attenuated in mice fed the 2 % (w/w) cholesterol diet. However, blocking cholesterol absorption reversed the cholesterol-feeding effect. Consistent with a suppressive effect of cholesterol on enterocytic amyloid-beta abundance, atorvastatin, an inhibitor of cholesterol biosynthesis, enhanced amyloid-beta. However, providing exogenous cholesterol abolished the atorvastatin-induced effect. In contrast to the suppression of enterocytic amyloid-beta by dietary cholesterol, mice fed a diet enriched in SFA had markedly greater abundance. Collectively, the findings suggest that exogenous and endogenous cholesterol reduce amyloid-beta concentration in enterocytes by suppressing production, or enhancing secretion associated with postprandial lipoproteins. Intestinally derived amyloid-beta will contribute to the pool of plasma protein and may influence cerebral amyloid homeostasis by altering the bi-directional transfer across the blood-brain barrier. SN - 1475-2662 UR - https://www.unboundmedicine.com/medline/citation/18631412/The_effect_of_exogenous_cholesterol_and_lipid_modulating_agents_on_enterocytic_amyloid_beta_abundance_ L2 - https://www.cambridge.org/core/product/identifier/S0007114508012269/type/journal_article DB - PRIME DP - Unbound Medicine ER -