Regional Innovation Strategy Promotion Program Sapporo Health Innovation 'Smart-H'

High fat foods, particularly those with high sucrose contents, are believed to be one of the causes of metabolic syndrome. Those foods have also been found to cause changes in the intestinal flora. Similar changes in intestinal flora can be induced by the oral administration of bile acid. Through the profile analysis of the bile acid in the intestine and the analysis of intestinal flora, we can clarify the mechanism by which high fat foods cause metabolic syndrome. Furthermore, we can establish an experimental model to clarify the effect of food microorganisms, such as lactic acid bacilli and bifidobacteria, on the innate immunity of intestinal mucosa and adipose tissue.

Over 70% of food with health claims focusing on living body adjusting functionalities, such as “Food for Specified Health Use (FOSHU) and health-promotion food, fulfills its functions by associated with bowel actions. Health promotion foods may be divided into two broad categories when classifying them by scene where they exercise their functionalities. One is the group which functions after absorption through intestinal tract. The other group has a functional role before absorption because of poorly-absorbed property. The former one is health promotion foods for people who are concerned about blood pressure, neutral fat and bone health, and the latter is effective for improvement of intestinal bacterial flora and for control of digestion absorption of nutrients.

As many have noted, there is a close relation between “functionality” and “absorption” of foodstuffs. This study aims to forge the platform for assessment of absorption and activity in nutrients of food functionalities on the basis of “separation & analysis”, “digestion & absorption”, and “food immunology” of food ingredients in collaboration with Faculty of Health Sciences, Faculty of Advanced Life Science and Faculty of Pharmaceutical Sciences of Hokkaido University.

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1. Development of separation and analysis system of food ingredients by applying proteomics
2. Mechanism analysis of digestion and absorption of foodstuffs based on pharmacokinetics
3. Evaluation of functionalities by using small-intestinal epithelial cells (epithelial enteroids) based on the perspective of food immunology

It becomes more obvious that ectopic fat accumulation is a more serious problem than deposition of cholesterol with respect to adiposis. Ectopic lipids cannot be diagnosed in conventional blood tests because they are distributed inside cells. In this study, in addition to measuring trace amounts of neutral lipid at nanomolar levels which are undetectable by conventional methods, we will make it possible to determine the quantity of lipid stored within cells and will develop an assessment system focusing on obesity and lipid oxidation. We are performing these joint research and commissioned analysis projects using the various lipid analysis apparatus integrated into the Laboratory for Advanced Lipid Analysis.

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1. Commissioned analysis using the Laboratory for Advanced Lipid Analysis
2. Formation of an information network
3. Analysis of lipids within single cells
4. Development of sports foods
5. Development of carbon nano tube sensors
6. Identification and commercialization of the health benefits of oysters

Naoki Morita, Group Leader, Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology Hokkaido (AIST Hokkaido)

“Nuclear receptor assay system” is one of the most useful methods to evaluate functionalities of food. AIST Hokkaido possesses over 20 varieties of receptor assay for evaluation. That is the nation’s largest number. AIST Hokkaido also has advanced its research in order to facilitate assay systems and to reduce costs through the development of basic technologies of the world’s first nuclear receptor assay by luminescence of secretional luciferase. In this project, AIST Hokkaido will transfer the nuclear receptor assay technology to a private business which has its own animal testing system. It is expected the establishment of analysis service for functionalities of foodstuffs in Hokkaido by integrating of both technologies.

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1. Establishment of nuclear receptor assay system through secretory luciferase for industrial use
2. Technology transfer of nuclear receptor assay system to private businesses
3. Establishment of functional substance analysis service by integration of nuclear receptor assay system and animal testing system

Nobutaka Wakamiya, Professor, School of Medicine, Asahikawa Medical University

The Research Center for Anti-oxidation Activity Analyses of Asahikawa Medical University has been analyzing the anti-oxidation ability of Hokkaido’s foodstuffs. The analyzed data and information of food ingredients are maintained in the antioxidant ingredient database and some of them have been released on the website. This study aims to improve infrastructure for research on food functionalities by the involvement of medical scientists and to establish an objective and transparent evaluation system focusing on antioxidative function of food with evidence-based analysis including clinical trials.

Furthermore, this study conducts not only analysis of antioxidative function of foodstuffs and clinical trials involving a group of volunteers but also fulfills a role in the field of dietary education utilizing local food products for local residents including medical experts, patients and the patients’ families.

＜Sub-projects＞

1. Establishment of a clinical evaluation system for the antioxidant functions of food
2. Development of a model for clinical intervention studies for food and supplements
3. Development of human resources for food science
4. Establishment of an internationally-comparable antioxidant ingredient database

Jun Nishihira, Professor, Faculty of Medical Informatics, Hokkaido Information University

The “Ebetsu Model” for human clinical trials for food has been conducted at the Health Information Science Center, Hokkaido Information University. It has been developed in close collaboration with local community within the framework of the Regional Innovation Strategy Promotion Program. Through the “Ebetsu Model”, researchers accumulate scientific evidence of the functionalities of foods, promote the general health conditions of community residents by utilizing foods rich in functionalities for maintaining and promoting health. Taking advantage of the model, the projects aim at the establishment of total healthcare system which integrates regional health promotion, preventive healthcare and nursing care support.

Concurrently, globalization will be pushed forward in partnership with local research institutions such as Hokkaido University Research & Business Park, National Institute of Advanced Industrial Science and Technology Hokkaido and regional research institutes. This partnership will encourage the regional development by contributing to structuring the global food valley. Furthermore, human clinical trials utilizing foods with functionalities will seek cooperation from research institutes and businesses in Asia, Europe and the United States in order to make progress of “Informatics relating to food and health” on a global scale based on scientific assessment data obtained from the research.

＜Sub-projects＞

1. Enhancement of the human clinical trials and study on health informatics
2. Development of a base toward globalization in study of nutrigenomics
3. Establishment of the base for regional research and network relating to food and information

The use of marine collagen has attracted attention due to the low risk of infectious pathogens compared with animal collagen. It becomes obvious that sturgeon collagen (especially type-II) has excellent characteristics such as a high denaturation temperature and high water affinity. This competence is expected to be used in areas of cosmetics (moisture retention, etc.) and medical supplies (substrate for cartilage regeneration, etc.). Together with advanced research into the use of sturgeon collagen, we will develop sturgeon farming techniques for caviar to expand on its use for promoting regional industry developments.

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1. Developing sturgeon farming techniques
2. Researching cosmetic and medical uses for sturgeon collagen, focusing on type-II collagen

We will elucidate whether functional materials in foods (sphingolipids, ceramides) are absorbed from the intestinal tract and will clarify the mechanism of the functionalities of absorbed materials. With the results of our research, we will develop new pharmaceuticals and utilize the fruits of our research in new industries. In addition, we will establish a hub of research and development by cooperating with companies through joint research as well as creating a world-class network of researchers, the "Sphingo Cluster".

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1. The development of a three dimensional model of skin and the screening methods for food materials
2. Development of ceramide-containing foods with the aim of cancer treatment and preventing cancer recurrence such 　as in tongue cancer and others.
3. Nutri-epigenomic analysis based on ceramide-containing foods
4. Enhanced fat metabolism and obesity prevention with yeast-derived phytoceramide-containing foods
5. Experimental study on the effects of ceramide-containing foods for Alzheimer' s disease prevention

"The Entirely Artificial Environment Plant Factory" can control all conditions that are required to grow plants such as temperature and lighting. By utilizing the plant factory, we have established cultivation techniques of galenic plants of which supply depends largely on overseas.

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1. Establishment of supply system for excellent quality seedlings
2. Establishment of cultivation techniques that allow stable production throughout the year
3. Development of cultivation techniques to increase the medicinal and functional content of galenic plants

Mushrooms exercise their various bio-functionality through an intestinal environment which is affected by intestinal bac-terial flora. However, the details of the mechanism are not yet clear. This research will evaluate the effects of dietary fiber and protein of the Taisetsu Hana No Mai No.1(the Hen of the Wood) on the enteral environment, and to clarify the mechanism of lipid metabolism and natural immunity enhancing effects brought by the changes in the intestinal environment. Moreover, based on the scientific evidence by the human interventional test, the Taisetsu Hana No Mai No.1 will be promoted as a functional food with the prebiotic effects.

Research and development regarding improvement in total sea urchin utilization will be carried out. The sea urchins which live in rocky-shore denudation areas are unsuitable for consumption and may be a cause of rocky-shore denudation themselves. The research laboratory has developed a system that effectively cultures the unused sea urchins. This project will aim to develop and commercialize prebiotic functional food that benefits human health by utilizing sea urchins which are not well grown despite that system.

Based on the fundamental research results related to influenza and respiratory diseases from the Research Center for Zoonosis Control, we will develop and commercialize adjuvants for infection inhibitors and vaccines, as well as therapeutic drugs and vaccines to prevent worsening of influenza and respiratory diseases.

We are developing the world-leading real-time tumor-tracking Proton Beam Therapy System with Molecular Imaging, which is used in the medical treatment for liver cancer and other diseases. Based on the results of clinical research, we will establish a research platform for the "Program of Disease Prevention, Diagnosis, and Treatment Planning" which will meet international standards. We will also invite researchers worldwide to share disease information and treatment expertise.

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1. Development of proton beam therapy systems
2. Development of a system for sharing patient treatment information

In the effort to prevent against obesity by appropriately utilizing 'physical exercise' and 'food habits', this study will develop methods to assess and analyze the effectiveness of 'physical exercise' with a focus on myokine and brain-derived neurotrophic factors (BDNF). Furthermore, the research on the regional foodstuffs associated with the secretion of these substances will be conducted. First of all, the current status of immobilization of Hokkaido citizens will be analyzed. Based on the results of the survey, the fundamental physical strength, skeletal muscle mass, and amount of physical exertion which may contribute to extend a healthy life expectancy will be investigated. The optimal biomarkers will be obtained. Based on the findings from the study, assistive devices for physical exercise and guidelines for kinetic and behavior therapy adapted to cold and snowy regions will be developed. Consequently, by maximizing accumulated scientific knowledge, an innovation hub as well as anti-obesity science will be created.

In Hokkaido, various types of cohort studies are conducted in cooperation with local communities, mainly by Sapporo Medical University. Through the utilization of these organizational frameworks and databases, the long-term effects on health caused by Hokkaido's foodstuffs will be considered as well as the awareness toward health of local residents will be evaluated.