DHA supplemented in peptamen diet offers no advantage in pathways to amyloidosis: is it time to evaluate composite lipid diet?
DHA supplemented in peptamen diet offers no advantage in pathways to amyloidosis: is it time to evaluate composite lipid diet?
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补充甲状腺素饮食中补充的DHA在淀粉样变性的途径中没有任何优势：是时候评估复合脂质饮食了吗？
DOI：
10.1371/journal.pone.0024094
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Rozmahel RF
中科院分区：
文献类型：
--
作者：
Amtul Z;Keet M;Wang L;Merrifield P;Westaway D;Rozmahel RF
许多报告已经证明了膳食二十二碳六烯酸（DHA）对β-淀粉样蛋白产生和阿尔茨海默病（AD）的有益作用。然而，这些研究都没有检查和比较二十二碳六烯酸与其他膳食营养素结合对斑块发病机制的影响。DHA与其他膳食营养素和脂肪酸的潜在相互作用通常被忽视。在这里，我们研究了DHA与两种饮食制度; peptamen（PEP+DHA）和低脂饮食（低脂+DHA）。Peptamen基础流质饮食是胃肠道功能障碍患者的标准单一来源营养。在这里，我们证明了一个强大的AD转基因小鼠模型显示出增加的趋势，产生β-淀粉样肽和淀粉样蛋白斑块时，喂养PEP+DHA的饮食。β-淀粉样肽的增加是由于β-分泌酶淀粉样前体蛋白（APP）裂解酶（BACE）、APP的蛋白水解C-末端片段β水平的升高趋势和内蛋白水解β-淀粉样蛋白的胰岛素降解酶水平的降低。相反，低脂+DHA饮食（基于脂肪摄入量减少约18%）的TgCRND 8小鼠改善了abeta肽的产生，并因此改善了淀粉样蛋白斑块。我们的工作不仅证明了DHA与肽胺一起服用时可能会对淀粉样斑块的形成产生不利影响，而且还加强了研究复合脂质或营养素而不是单一脂质或营养素对斑块发展重要途径的影响的重要性。
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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影响因子：
4.7
作者：
Bate, Clive;Marshall, Victoria;Williams, Alun
通讯作者：
Williams, Alun
影响因子：
4.1
作者：
Ando, H;Wen, ZM;Hearing, VJ
通讯作者：
Hearing, VJ
影响因子：
5.3
作者：
Christensen, MA;Zhou, WH;Song, WH
通讯作者：
Song, WH
DOI：
10.1073/pnas.0230450100
发表时间：
2003-04-01
影响因子：
11.1
作者：
Farris, W;Mansourian, S;Guénette, S
通讯作者：
Guénette, S
影响因子：
16.2
作者：
Calon, F;Lim, GP;Cole, GM
通讯作者：
Cole, GM