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Molecular Form of Dietary DHA and its Bioavailability for the Brain

膳食 DHA 的分子形式及其对大脑的生物利用度

基本信息

批准号：
8900973
负责人：
PAPASANI V SUBBAIAH
金额：
$ 23.21万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8900973
关键词：
Abbreviations Acids Adipose tissue Adult Age Alzheimer&apos s Disease Appearance Attenuated Biological Availability Blood - brain barrier anatomy Blood Circulation Brain Caco-2 Cells Cholesterol Esters Chylomicrons Cleaved cell Cognitive deficits Diet Dietary Phospholipid Diffusion Docosahexaenoic Acids Eagles Esters Euphausiacea Fatty Acids Fish Oils Fistula Gas Chromatography Gas-Liquid Chromatography Goals Health High Density Lipoproteins Human Hydrolysis Intestinal Absorption Intestines Lead Lecithin Linolenic Acids Lipase Lipids Lipoproteins Liver Lymph Lysophosphatidylcholines Mass Spectrum Analysis Mental Retardation Molecular Monoglycerides Neurons Nonesterified Fatty Acids Nutraceutical Oils Omega-3 Fatty Acids Organ Pancreas Pancreatic enzyme Phosphatidylethanolamine Phospholipase A2 Phospholipids Plasma Positioning Attribute Preparation Prevention Rattus Relative (related person)Schizophrenia Source Testing Tissues Triglycerides absorption dietary supplements feeding healthy aging high density lipoprotein phosphatidylcholine improved in vitro Model in vivo Model mouse model nervous system disorder novel particle prevent uptake

项目摘要

DESCRIPTION (provided by applicant): DHA (docosahexaenoic acid) is an omega-3 fatty acid that is absolutely essential for the normal function of the brain, and its deficiency is known to be associated with several neurological disorders including Alzheimer's disease (AD), mental retardation, and schizophrenia. Although the brain contains the highest concentration of DHA among the organs, it is unable to synthesize DHA from the precursors, and needs to obtain it mostly from the diet. However, the presently available dietary supplements (fish oil, ethyl esters, krill oil, etc.) are inefficient in increasing the brain DHA levels, although they all easily enric the other organs with DHA. One possible reason for this is that while all other organs take up DHA in the form of whole lipoprotein particles, the brain takes it up through molecular diffusion of th DHA-containing lipids through the blood brain barrier, the most efficient carrier of DHA being lysophosphatidylcholine (LPC). Thus, the presence of DHA in plasma phospholipids is crucial for its brain uptake, and consequently, the absorption of dietary DHA in the form of phospholipids, rather than as triacylglycerol (TG), is highly advantageous. However, the presently available supplements of DHA are all absorbed as TG, because DHA in them is released as free fatty acid in the intestinal lumen by the pancreatic lipase and phospholipase A2, and incorporated into chylomicron TG. In this exploratory project, we will test the hypothesis that supplying the DHA as the sn-1 ester of phosphatidylcholine (PC) would result in its absorption as phospholipid because it escapes hydrolysis by the pancreatic enzymes, and thus will be more available for the eventual uptake by the brain. In Aim 1, we will study the absorption of different molecular forms of DHA (free acid, TG, sn-1 ester of PC, sn-2 ester of PC, and as LPC) employing an in vitro model (Caco-2 cells) as well as an in vivo model (lymph fistula rat). The relative amounts of DHA found in TG and PC of the absorbed lipids will be determined by tandem mass spectroscopy and gas chromatography. In Aim 2, we will feed the various molecular forms of DHA as supplements to the normal diets of adult rats for 4 weeks, and determine its appearance in plasma phospholipids, as well as its accumulation in the liver, adipose tissue and brain. If the proposed hypothesis is correct, the accumulation of DHA in the brain should be highest when it is present in the diet as sn-1 ester of PC or LPC. The results from these studies could lead to novel nutraceutical approaches to achieve adequate brain DHA levels for healthy aging and for prevention of neurological diseases such as AD, mental retardation, and schizophrenia.

描述（由申请人提供）：DHA（二十二碳六烯酸）是一种 omega-3 脂肪酸，对大脑的正常功能至关重要，但其缺乏是已知的与多种神经系统疾病有关，包括阿尔茨海默病 (AD)、智力低下和精神分裂症。虽然大脑中DHA含量是器官中最高的，但它无法从前体合成DHA，大部分需要从饮食中获取。然而，目前可用的膳食补充剂（鱼油、乙酯、磷虾油等）虽然很容易使其他器官充满 DHA，但在增加大脑 DHA 水平方面效果不佳。一个可能的原因是，虽然所有其他器官都以全脂蛋白颗粒的形式吸收 DHA，但大脑是通过含 DHA 的脂质通过血脑屏障的分子扩散来吸收的，DHA 最有效的载体是溶血磷脂酰胆碱 (LPC)。因此，血浆磷脂中 DHA 的存在对于大脑的吸收至关重要，因此，以磷脂形式而不是三酰甘油 (TG) 形式吸收膳食 DHA 是非常有利的。然而，目前市面上的DHA补充剂都是以TG的形式被吸收，因为其中的DHA在肠腔内被胰脂肪酶和磷脂酶A2以游离脂肪酸的形式释放出来，并掺入乳糜微粒TG中。在这个探索性项目中，我们将测试以下假设：以磷脂酰胆碱 (PC) sn-1 酯的形式提供 DHA 会导致其以磷脂的形式被吸收，因为它可以逃脱胰腺酶的水解，因此更容易被大脑最终吸收。在目标 1 中，我们将采用体外模型（Caco-2 细胞）和体内模型（淋巴瘘大鼠）研究不同分子形式的 DHA（游离酸、TG、PC 的 sn-1 酯、PC 的 sn-2 酯和 LPC）的吸收。吸收脂质的TG和PC中发现的DHA的相对量将通过串联质谱法和气相色谱法测定。在目标 2 中，我们将用各种分子形式的 DHA 作为成年大鼠正常饮食的补充剂喂养 4 周，并测定其在血浆磷脂中的出现，以及其在肝脏、脂肪组织和大脑中的积累。如果所提出的假设是正确的，那么当 DHA 以 PC 或 LPC 的 sn-1 酯形式存在于饮食中时，DHA 在大脑中的积累应该是最高的。这些研究的结果可能会带来新的营养保健方法，以达到足够的大脑 DHA 水平，从而实现健康老龄化并预防 AD、智力低下和精神分裂症等神经系统疾病。