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：
8755224
负责人：
PAPASANI V SUBBAIAH
金额：
$ 19.94万
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 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8755224
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 Defect Diet Dietary Phospholipid Diffusion Docosahexaenoic Acids Eagles Esters Euphausiacea Fatty Acids Fish Oils Fistula Gas Chromatography Gas-Liquid Chromatography Goals 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 public health relevance 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（Docosahexaenoic Acid）是一种omega-3脂肪酸，对大脑的正常功能绝对必不可少，并且其缺乏症已知与几种神经系统疾病有关，包括阿尔茨海默氏病（AD），智力低下和精神分裂症。尽管大脑在器官中含有最高的DHA浓度，但它无法从前体中综合DHA，并且需要主要从饮食中获得。但是，目前可用的饮食补充剂（鱼油，乙酯，磷虾油等）在提高大脑DHA水平的效率低下，尽管它们都很容易与其他器官一起使用DHA。这样做的一个可能原因是，尽管所有其他器官都以整个脂蛋白颗粒的形式占据DHA，但大脑通过含DHA的脂质的分子扩散通过血液脑屏障将其抬高，DHA最有效的DHA是溶血磷脂酰胆碱（LPC）。因此，血浆磷脂中DHA的存在对于其脑摄取至关重要，因此，以磷脂的形式吸收饮食DHA，而不是三酰基甘油（TG），这是非常有利的。但是，目前可用的DHA补充剂都被吸收为TG，因为其中的DHA被胰腺脂肪酶和磷脂酶A2释放为肠腔中的游离脂肪酸，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：DHA作为磷脂酰胆碱的SN-1酯（PC）将导致其作为磷脂的吸收，因为它可以通过胰腺酶避免水解，因此将更多地用于大脑的最终吸收。在AIM 1中，我们将研究采用体外模型（CACO-2细胞）以及体内模型（淋巴结大鼠）的不同分子形式的DHA（游离酸，TG，SN-1酯，PC的SN-1酯，PC的SN-2酯，作为LPC）的吸收。吸收脂质的TG和PC中发现的相对量将由串联质谱和气相色谱法确定。在AIM 2中，我们将以DHA的各种分子形式为成年大鼠的正常饮食提供4周的补充，并确定其在血浆磷脂中的外观，及其在肝脏，脂肪组织和大脑中的积累。如果提出的假设是正确的，那么当DHA在饮食中以PC或LPC的SN-1酯形式存在时，DHA在大脑中的积累应最高。这些研究的结果可能导致新颖的营养方法，以达到足够的脑DHA水平以健康衰老，并预防AD，智力低下和精神分裂症等神经系统疾病。