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Impact of dietary fat and obesity on biotransformation, tissue distribution and bioactivity of isoflavones

膳食脂肪和肥胖对异黄酮生物转化、组织分布和生物活性的影响

基本信息

批准号：
191837604
负责人：
Professorin Dr. Sabine E. Kulling, Ph.D.
金额：
--
依托单位：
Institut für Physiologie und Biochemie der Ernährung
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2011
资助国家：
德国
起止时间：
2010-12-31 至 2014-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/191837604?language=en
关键词：
Impact dietary fat obesity biotransformation

项目摘要

The bioavailability and the complex biotransformation of isoflavones (IF), which are both highly variable among individuals, have a substantial impact on their biological activity and thus on outcomes from clinical as well as animal studies. Based on our previous finding that around 45% of IF and their metabolites are associated to plasma lipoproteins (LP), we postulate that LP might be important vectors for IF to access target tissues. Therefore, factors which influence the amount and composition of circulating LP might affect the IF-LP association and IF distribution within LP subclasses. As a consequence IF bioavailability, IF tissue concentration and in the end the biological activity could be altered. In this project, we will focus on two factors which on one hand have an impact on the plasma LP profile and on the other hand are associated with an increased breast cancer risk in postmenopausal women: obesity and high intake of dietary fat. In one short-term and one long-term human intervention study with postmenopausal women, the following questions will be answered: 1) Do total body fat mass and/or a high intake of dietary fat confer changes in IF metabolism and distribution to target tissues? 2) What is the role of the LP? 3) Do the variations in bioavailability and metabolism alter IF bioactivity on mammary cancer- and obesity-related biomarkers? 4) Does regular IF consumption modulate obesityrelated DNA-methylation changes? To allow better transferability of animal studies to the human situation, and to characterize species (human/rat) specific differences in the bioavailability and biotransformation the same questions will be addressed in comparable studies with Wistar rats.

异黄酮（IF）的生物利用度和复杂的生物转化在个体之间高度可变，对其生物活性产生重大影响，从而对临床和动物研究的结果产生重大影响。基于我们之前的发现，大约45%的IF及其代谢物与血浆脂蛋白（LP）相关，我们假设LP可能是IF进入目标组织的重要载体。因此，影响循环低脂血数量和成分的因素可能会影响低脂血的关联和低脂血在低脂血亚类中的分布。因此，IF的生物利用度、IF组织浓度以及最终的生物活性都可能被改变。在这个项目中，我们将重点关注两个因素，这两个因素一方面影响血浆LP谱，另一方面与绝经后妇女乳腺癌风险增加有关：肥胖和高膳食脂肪摄入。在一项针对绝经后妇女的短期和长期人类干预研究中，将回答以下问题：1)身体总脂肪量和/或高膳食脂肪摄入量是否会改变IF代谢和目标组织的分布？2) LP的作用是什么？3)生物利用度和代谢的变化是否会改变IF在乳腺癌和肥胖相关生物标志物上的生物活性？4)规律的IF消费是否会调节肥胖相关的dna甲基化变化？为了使动物研究更好地转移到人类情况，并表征物种（人类/大鼠）在生物利用度和生物转化方面的具体差异，将在Wistar大鼠的可比研究中解决相同的问题。