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。有些食物提供更多的好处，而不仅仅是它们的营养价值，这些食物被称为“功能性食品”。“功能性食品”一词是20世纪80年代在日本提出的。从那时起，数百种功能性食品在世界各地生产和销售。我从1990年代中期开始从事这方面的研究。我的研究团队为我们理解植物甾醇（植物甾醇和甾烷醇）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。植物甾醇由所有植物产生，可降低人体血液中的胆固醇水平。最近，我们阐明了其他几种食物，包括野生稻，萨斯卡通浆果和野生西瓜籽对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/或配制新型营养品和/或活性药物成分的新方法，以保护生理胆固醇和葡萄糖代谢。以下2个目标是我未来5年的短期目标：目标1：建立植物甾醇对小鼠模型中生理性胆固醇代谢和正常血管功能的作用的新机制。目的2：研究萨斯卡通浆果对小鼠生理性糖代谢的影响。材料和方法：将使用胆固醇和葡萄糖代谢的雄性和雌性小鼠模型。在12-24周内，用补充有或没有植物甾醇或萨斯卡通浆果的适当实验饮食喂养小鼠。 重要性：拟议的研究符合NSERC的任务，因为它们旨在阐明功能性食品对健康状态下生理胆固醇和葡萄糖代谢的作用机制。拟议中的研究将产生数据，这些数据将有助于了解膳食制剂如何保持生物系统的完整性。我们的数据将为新型营养品和/或活性药物成分的开发提供新的方向，从而提交专利申请。这对加拿大农业、卫生和经济部门产生了积极影响。这些研究允许培训若干研究生和本科生。学生将了解功能性食品如何影响生理器官功能，从而有助于该领域的未来研究和发展。这些受训人员将有机会在我们的多学科设施中获得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、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.