DHA Supplemented in Peptamen Diet Offers No Advantage in Pathways to Amyloidosis: Is It Time to Evaluate Composite Lipid Diet?

被引:18
作者
Amtul, Zareen [1 ,2 ]
Keet, Mary [1 ,2 ]
Wang, Lin [2 ]
Merrifield, Peter
Westaway, David [3 ]
Rozmahel, Richard F. [1 ,2 ]
机构
[1] Univ Western Ontario, Dept Biochem, London, ON, Canada
[2] Lawson Hlth Res Inst, London, ON, Canada
[3] Univ Alberta, Ctr Prions & Prot Folding Dis, Edmonton, AB, Canada
来源
PLOS ONE | 2011年 / 6卷 / 09期
基金
加拿大健康研究院;
关键词
DOCOSAHEXAENOIC ACID; ALZHEIMERS-DISEASE; TRANSGENIC MICE; NERVOUS-SYSTEM; ELEMENTAL DIET; PEPTIDE LEVELS; BETA-PROTEIN; MOUSE MODEL; IN-VIVO; HIV;
D O I
10.1371/journal.pone.0024094
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Numerous reports have documented the beneficial effects of dietary docosahexaenoic acid (DHA) on beta-amyloid production and Alzheimer's disease (AD). However, none of these studies have examined and compared DHA, in combination with other dietary nutrients, for its effects on plaque pathogenesis. Potential interactions of DHA with other dietary nutrients and fatty acids are conventionally ignored. Here we investigated DHA with two dietary regimes; peptamen (pep+DHA) and low fat diet (low fat+DHA). Peptamen base liquid diet is a standard sole-source nutrition for patients with gastrointestinal dysfunction. Here we demonstrate that a robust AD transgenic mouse model shows an increased tendency to produce beta-amyloid peptides and amyloid plaques when fed a pep+DHA diet. The increase in beta-amyloid peptides was due to an elevated trend in the levels of beta-secretase amyloid precursor protein (APP) cleaving enzyme (BACE), the proteolytic C-terminal fragment beta of APP and reduced levels of insulin degrading enzyme that endoproteolyse beta-amyloid. On the contrary, TgCRND8 mice on low fat+DHA diet (based on an approximately 18% reduction of fat intake) ameliorate the production of abeta peptides and consequently amyloid plaques. Our work not only demonstrates that DHA when taken with peptamen may have a tendency to confer a detrimental affect on the amyloid plaque build up but also reinforces the importance of studying composite lipids or nutrients rather than single lipids or nutrients for their effects on pathways important to plaque development.
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页数:8
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