An Investigation of the mechanisms of action for the effects of dietary phytosterols and Saskatoon berries on physiologic cholesterol and glucose metabolism in experimental mice: The crosstalk between gut microbiota and functional foods

背景：遗传和饮食是影响生理器官功能的两个主要因素。有些食物除了营养价值外，还有更多的好处；这些食物被称为“功能性食品”。“功能性食品”一词是20世纪80年代在日本制造的。从那时起，全世界已经生产和销售了数百种功能性食品。自20世纪90年代中期以来，我一直参与这一领域的研究。我的研究团队为我们了解植物甾醇(植物甾醇和甾醇)如何影响实验小鼠的生理胆固醇代谢和心血管功能做出了贡献。植物甾醇是由所有植物产生的，可以降低人类血液中的有害胆固醇水平。最近，我们阐明了其他几种食物，包括野生大米、萨斯卡通浆果和野生西瓜籽对小鼠模型正常血管功能以及葡萄糖和胆固醇代谢的影响机制。我的长期目标是开发合成和/或配制新的营养食品和/或活性药物成分的新方法，以保持生理胆固醇和葡萄糖代谢。以下两个目标是我今后5年的短期目标：目标1：建立植物甾醇对小鼠生理胆固醇代谢和正常血管功能影响的新的作用机制。目的：研究沙棘果对实验小鼠生理性糖代谢的影响。材料和方法：将使用雄性和雌性小鼠的胆固醇和葡萄糖代谢模型。在12-24周内，小鼠将被喂以添加或不添加植物类固醇或萨斯卡通浆果的适当实验饲料。意义：建议的研究符合NSERC的任务，因为它们旨在阐明健康状态下功能性食品对生理性胆固醇和葡萄糖代谢的影响的作用机制。拟议的研究将产生数据，这些数据将有助于理解饮食制剂如何维护生物系统的完整性。我们的数据将为新型营养食品和/或活性药物成分的开发提供新的方向，从而导致专利申请(S)。这对加拿大农业、卫生和经济部门产生了积极影响。这些研究可以培养几名研究生和本科生。学生将获得功能食品如何影响生理器官功能的知识，从而为该领域未来的研究和发展做出贡献。这些学员将有机会接触到我们多学科设施中的最先进的设备和专业知识，这些设施位于马尼托巴大学的食品和人类营养科学系、医学微生物学和化学系以及圣博尼法斯医院研究中心。

BACKGROUND: Genetics and diets are 2 main contributing factors to physiologic organ function. Some foods offer more benefits than just their nutritional values; these foods are called "functional foods." The term "functional foods" was made in Japan in 1980s. Since then hundreds of functional foods have been produced and marketed worldwide. I have been involved in this area of research since mid 1990s. My research team has contributed to our understanding of how phytosterols (Plant sterols and stanols) impact physiologic cholesterol metabolism and cardiovascular function in experimental mice. Phytosterols are produced by all plants and reduce blood bad cholesterol levels in humans. More recently, we elucidated the mechanisms of the effects of several other foods, including wild rice, Saskatoon berries, and wild watermelon seeds on normal vessel function as well as glucose and cholesterol metabolism in mouse models. My long-term goal is to develop new ways of synthesizing and/or formulating novel nutraceuticals and/or active pharmaceutical ingredients for preserving physiologic cholesterol and glucose metabolism. The following 2 objectives are my short-term objectives for the next 5 years: OBJECTIVE 1: To establish a new mechanism of action for the effects of phytosterols on physiologic cholesterol metabolism and normal vascular function in mouse models. OBJECTIVE 2: To establish how Saskatoon berries affect physiologic glucose metabolism in experimental mice. MATERIALS AND METHODS: Both male and female mouse models of cholesterol and glucose metabolism will be used. The mice will be fed with appropriate experimental diets supplemented with or without phytosterols or Saskatoon berries over 12-24 weeks. SIGNIFICANCE: The proposed studies are in line with NSERC's mandates, because they are designed to elucidate the mechanisms of action for the effects of functional foods on physiologic cholesterol and glucose metabolism in healthy state. The proposed studies will produce data that will shed light on understanding how dietary agents preserve the integrity of biological systems. Our data will provide new directions for development of novel nutraceuticals and/or active pharmaceutical ingredients, leading to filing patent application(s). This endorses a positive impact on the Canadian Agriculture, Health and Economy sectors. These studies allow training of several graduate and undergraduate students. The students will gain knowledge of how functional foods can impact physiologic organ function, thereby, can contribute to future research and development in this field. These trainees will have access to the state-of-the-art equipment and expertise in our multidisciplinary facilities available in the Departments of Food and Human Nutritional Sciences, Medical Microbiology and Chemistry at the University of Manitoba as well as St. Boniface Hospital Research Centre.