Tags

Type your tag names separated by a space and hit enter

The effect of exogenous cholesterol and lipid-modulating agents on enterocytic amyloid-beta abundance.

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.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    School of Biomedical Sciences, Curtin University of Technology, Perth, WA, Australia.

    , , , ,

    Source

    The British journal of nutrition 101:3 2009 Feb pg 340-7

    MeSH

    Amyloid beta-Peptides
    Animals
    Anticholesteremic Agents
    Atorvastatin
    Azetidines
    Body Weight
    Cholesterol
    Cholesterol, Dietary
    Enterocytes
    Ezetimibe
    Female
    Heptanoic Acids
    Hydroxymethylglutaryl-CoA Reductase Inhibitors
    Immunohistochemistry
    Intestinal Absorption
    Mice
    Mice, Inbred C57BL
    Pyrroles
    Random Allocation
    Triglycerides

    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 -