The origin of pre-symptomatic illness and preventive measures through diet

Professor Satoshi Ishizuka

Affiliation: Graduate Research Faculty of Agriculture, Graduate Graduate School of Agriculture (Department of Biofunctional Chemistry School of Agriculture)

Specialized field: food nutrition science

Research Keywords: Metabolic Syndrome, Mebyou, Mebyou

Alma mater: Tokyo Institute of Technology High School

Final academic background: Graduate School of Agriculture, Hokkaido University

HP address:

*This article is a re-edited version of the article published in the 4th issue of "Frontiers of Knowledge". Updated December 6, 2022

What made you start your current research?

Until my master's degree in graduate school, I was researching low-molecular-weight compounds involved in the flavor of cheese during ripening. As my research progressed, my interest began to shift from "food" itself to "effects of food on the eating side," and I obtained my doctoral degree in research on the mechanism by which dietary fiber suppresses the onset of colon cancer. Nowadays, food with function claims is commonplace, but at that time, such efforts were widespread as research. Even before that, I had been researching the effects of food on the eating side in the food and nutrition research laboratory to which I currently belong. Here, while exploring the onset mechanisms of diseases that occur in organs such as the gastrointestinal tract and liver, which are the centers of nutrient metabolism, we have been conducting research on food ingredients and eating methods that contribute to the prevention of such pathologies. Since we belong to School of Agriculture, I think we should think about what kind of diet can reduce the risk of developing pathological conditions, rather than treating diseases that have already occurred.

What kind of equipment are you using and what kind of experiments are you doing?

Fig. 1 Rearing of rats Health status is monitored while food intake and body weight are recorded in individual cages.

Various biochemical tests and instrumental analyzes can be used to investigate changes in metabolism caused by adding and removing ingredients contained in experimental animal feed (Fig. 1). As you know, if the amount of energy you take in exceeds the amount of energy used during exercise, it will be stored in your body. In the so-called metabolic syndrome, cholesterol is an enemy. Cholesterol itself cannot be broken down in our body, but it can be converted into a substance called bile acid by attaching hydroxyl groups and carboxylic acids that make it compatible with water so that it can be taken out of the body. Bile acids are composed of diverse molecular groups, and their composition and concentration vary significantly depending on their location in the body. By extracting bile acids from various organs, gastrointestinal contents, feces, urine, blood, etc., and comprehensively analyzing them with a high-performance liquid chromatography mass spectrometer (Fig. 2) (Fig. 3), You can see how it "flows". Through such experiments, we have discovered the possibility of characteristic bile acid metabolism in metabolic syndrome. We found that such a change in the flow of bile acids creates a condition that facilitates the development of fatty liver. .

Figure 2 Bile acid metabolism analysis using high-performance liquid chromatography-mass spectrometer

Figure 3 Bile acid metabolism analysis

When we examined bile acid metabolism in rats fed a high-fat diet, we found that only a specific bile acid (12-hydroxy bile acid) increased. This 12-hydroxylated bile acid can be fed to rats to make their bile acid composition similar to that of a high-fat diet. We found that, when raised under these conditions for more than 10 weeks, various symptoms seen in lifestyle-related diseases, such as fluctuations in the intestinal flora, lipid accumulation in the liver, and deterioration of the gastrointestinal barrier function, were induced (Fig. 4). . Although these symptoms are not serious, they also found that inflammation made the symptoms worse. These findings suggest that 12-hydroxy bile acid triggers various symptoms of pre-symptomatic disease. In addition to individual-level nutritional experiments using rats as experimental animals, metabolic analysis experiments at the tissue and cell levels are essential for mechanism analysis. Using these facilities, equipment, and methods, we are conducting experiments to investigate not only the direct effects of food ingredients themselves, but also metabolic changes in the body depending on how we eat them. By carefully observing the events that occur in tissues and cells, we are conducting experiments to clarify the effects on the body caused by differences in diet and eating methods, especially problems.

Fig. 4 Symptoms induced in rats by 12-hydroxy bile acid

How does it relate to our lives?

Through animal experiments, we have found that minor metabolic fluctuations, such as those caused by differences in eating habits, create a state of presymptomatic disease, and we are working to elucidate the onset mechanism and factors involved in exacerbating symptoms. Depending on what kind of food you eat and how you eat it, you may or may not get sick easily. In a lecture for children held by School of Agriculture, when I provided a topic on food education, I planned to show a slide show of all the meals that I and the student staff had prepared over the course of seven days. Some people continue to eat well-balanced meals, but others do not. Through this experience, I realized again that "my common sense about food" is not always shared with others. Me-byo, which represents the pre-disease stage, can be rephrased as "a state that is not clearly ill, but is susceptible to illness." I am continuing my research with the hope that I can find a way to avoid pre-symptomatic disease caused by aging and eating habits and apply it to my daily eating habits.