Interview with Professor Noriyuki Yanaka
In this modern age, with the rise in people’s health consciousness, the functionality of food has been drawing increasing attention. What are the mechanisms that cause obesity and other diseases? Dr. Yanaka strives to clarify how food constituents work in the human body at the molecular and genetic levels.
Studies on the relationship between food and health at the molecular and genetic levels
Dr. Yanaka specializes in food nutritive function science, which is a science that clarifies the physiological functions and effects of nutrients and other components contained in food.

Dr. Yanaka’s studies have focused on two core themes. One is the clarification of the relationship between the onset of lifestyle diseases and the physiological functions of food. The other is the development of new concept foods.

“For example, the deficiency of a certain food or nutrient could cause a particular disease. I try to clarify what the mechanism is, namely, the relationship between food and disease,” Dr. Yanaka said.
Taking the nutrient “choline” as an example, Dr. Yanaka explained: “Choline is a nutrient typically ingested through eggs. The constituent of egg lecithin contains choline. The scientific name of lecithin is phosphatidylcholine.”

Although choline, which is regarded as a vitamin in other countries, is an essential nutrient, many people in developed countries are said to be deficient in it. “Choline is a component of acetylcholine, which acts as a neurotransmitter in the brain. It is known that the brains of patients with Alzheimer’s disease show lower levels of acetylcholine. In addition, choline deficiency is said to be related to non-alcoholic steatohepatitis (NASH), which is becoming more common these days,” Dr. Yanaka said.
Then, the members of Dr. Yanaka’s laboratory investigate what changes in the body are caused by choline deficiency as well as what foods we can obtain choline from and what forms of intake are more effective.

The approach used for these studies is the genome-editing method. Dr. Yanaka said, “We observe what changes occur to animals’ bodies when choline is removed from their diets by using the genome-editing method. If we simply remove choline from their diets without using the genome-editing method, various changes occur in their bodies in parallel, such as liver failure, decreased muscle function, and dementia in the brain. In this case, we cannot know what occurred first and what occurred due to the effect of the first and subsequent symptoms. Then, we create special mice by manipulating their genes to cause choline deficiency only in a specific organ, such as the liver or a muscle.” He said that by using this approach, they can see in detail at a cellular level what changes occur when there is a deficiency in the nutrient.
Successful creation of genetically modified mice, which enable observation of the initial lesion of kidney disease from outside their bodies
When advancing the above research, Dr. Yanaka discovered a new method to evaluate the functions of foods. “Successful creation of genetically modified mice, which enable observation of the initial lesion of kidney disease from outside their bodies”?this is a topic recently reported both within and outside Japan as the first achievement of its kind in the world.*

The details of this method are as follows: Firstly, a genetically modified mouse that produces chemiluminescence at the initial stage of kidney disease is created. After being continuously fed food containing adenine, which induces nephritis, the mouse eventually develops nephritis, and its kidneys produce luminescence. By taking an image of the mouse’s back by using a high-sensitivity imaging system, lesions of the kidneys can be observed from outside the body.

Dr. Yanaka said that by using this method, he could experimentally confirm whether the development of nephritis can be suppressed by taking glucosyl hesperidin, which is recognized as a potential functional food material, in a short period of one week. This means that the method has been confirmed as a way to rapidly evaluate whether a new function of food is effective or not.
  Furthermore, Dr. Yanaka said that this method has other advantages. “If we find that taking an ingredient for one week after recognizing a sign of a kidney disease can suppress the development of the disease, we will be able to propose that this ingredient may be effective for the prevention of the disease. Since we aim to propose new functions of foods to society, acceleration of our research by using this evaluation method is a major advantage. In addition, “observability from outside the body” means that the same mouse can be continuously monitored. In conventional animal experiments in which kidneys must be extracted for investigation, many animals are sacrificed to check the progression of disease. In this regard, this method can considerably reduce the number of sacrificed experimental animals,” Dr. Yanaka said.

The genetically modified mice are created by utilizing the on/off switch of the serum amyloid A3 (Saa3) gene, whose expression sharply rises in the kidney when nephritis develops by the induction of food containing adenine. The switch of the Saa3 gene is also turned on by the development of other inflammatory diseases, such as colitis and dermatitis. Therefore, Dr. Yanaka said that this method has high potential to be applied to various studies on these diseases, as well as nephritis.
"I want to enjoy discovering interesting things together with local communities and students"
Dr. Yanaka also places importance on connections with local communities in his studies. “We are often asked by local people, “Are there any ways to utilize this ingredient?” So, thinking that it is great if we can help them develop products while introducing locally produced ingredients, we started our research with this approach. In other words, this is a community-based research to develop products using ingredients produced in Hiroshima Prefecture while promoting the health benefits of the ingredients,” Dr. Yanaka said.

One example is the development of products using hassaku. Hiroshima Prefecture is a production area of citrus fruits. As a result of careful investigation, Dr. Yanaka’s research team selected hassaku as a particularly healthy ingredient among locally produced citrus fruits and communicated its health benefits. After that, in cooperation with several local food production companies, the team developed “Seto Komachi,” a confection using hassaku, and “Hassaku Marmalade,” both of which are currently available in the market and have acquired a good reputation.

While Dr. Yanaka is currently involved in various studies as described above, he worked at a pharmaceutical company for ten years before joining Hiroshima University as a faculty member. “I majored in agriculture at university. At that time, I was involved in research to create useful things by making use of microorganisms. I joined a pharmaceutical company to do work associated with this theme. However, just around the time when I joined the company, it stopped this kind of research on microorganisms as a company policy. I was very disappointed as I had lost my purpose to work at the company. But I subsequently changed my mind and studied very hard to develop drugs with new concepts,” Dr. Yanaka said.

Although the subject of his research has changed from drugs to food, his attitude of clarifying the relationship between the subject and diseases as well as the human body remains unchanged. He said that the pleasure in conducting research is “to receive a fair evaluation of a valuable finding even though it may be modest” and “to try to discover interesting things together with students while feeling that it’s worthwhile.” He also added: “As is the case with community-based research, the biggest pleasure is to share the feeling of fun and pleasure with somebody.”
Dr. Yanaka said that he will continue to look for unknown functions and effects of ingredients. His motto is “to enjoy working harmoniously together.”

Finally, as a message to young people who aim to become researchers, Dr. Yanaka said, “I want all of you to challenge yourselves in everything you do instead of giving up before even trying. Unsolvable problems are wonderful. You should think that there are unknown worlds behind them. For example, in a test, students often try to solve the easy problems first, avoiding the difficult ones that they cannot solve. In terms of efficiency, this is indeed a better way. But in the world of academic research, I think that this attitude becomes a crucial disadvantage. If you go a different way that you have avoided before, you may be able to encounter a new landscape and discover something new. I welcome young people who have such a willingness to take on new challenges in my laboratory.”

* This study was jointly conducted by Dr. Yanaka, Shigei Medical Research Institute, and Radboud University in the Netherlands. It was published on the website of the British science magazine “Scientific Reports.”
Noriyuki Yanaka
Professor, Laboratory of Moleculer Nutrition

April 7, 1991 – Researcher, Discovery Research Laboratory, Mitsubishi Tanabe Pharma Corporation
December 1, 2001 – Associate Professor, School of Applied Biological Science, Hiroshima University
April 1, 2002 – Associate Professor, School of Applied Biological Science, Hiroshima University
April 1, 2019 – Associate Professor, Graduate School of Integrated Sciences for Life, Hiroshima University
April 1, 2020 – present Professor, Graduate School of Integrated Sciences for Life, Hiroshima University

Posted on Feb 25, 2020