Lipidomics is Finally Coming! The Frontiers of Lipid Research and the Road to Health Value Creation

Lipid research, with its diverse functions, is now at a major turning point. Lipids are the building blocks of cell membranes, responsible for energy production and storage, and signal molecules for information transmission. The research field of "lipidomics" offers unlimited possibilities. Experts from various fields passionately discussed the next research hotspot, "lipidomics," following "genomics" and "proteomics.

speaker
Hiroki Nakanishi (Representative Director, Lipidome Labs, Inc.)
Hideo Shindo (National Center for Global Health and Medicine) [now National Institutes of Health and Crisis Management, JIHS].  (Director of Tenure Track Department / Adjunct Professor, Graduate School of Medicine, The University of Tokyo)
Makoto Mitarai (Manager, Innovation, Business Planning Department, Maruha Nichiro Corporation)

moderator
(President and CCO, LIVERNESS Corporation)

The "Finally Coming" Lipidomics Present

Inoue: Hello everyone. I am very pleased to have all of you oil lovers here. We have been given the title of lipidomics, and it is a very important topic. I am sure you have all heard of genomics and proteomics. You have probably also heard of metabolomics. However, although people have been saying for a long time that lipidomics is "coming, coming, coming," it has yet to really take off.

Shindo: They are coming.

Venue: Laughter

Inoue: No, no, I think that objectively speaking, they are not here yet.

Venue: Laughter

Shindo: They are coming.

Venue: Laughter

Inoue: Now (laughs), in your research, do you all think, "I have to examine lipids"? In biological research, we are going to examine genomes and mitochondria. Biomolecules composed of proteins are also important. Metabolomics, the study of metabolites from biological activities and their effects, is also attracting attention. However, the motivation to look at lipids is hard to find. The reason for this is that it is difficult to know the types of lipids that can be analyzed and how far the level of analysis has progressed. In this session, I would like to delve into the field of lipidomics and provide a road map for the creation of new health value.

Inoue: Today we will discuss with specialists in lipid research. Dr. Shindo from the National Center for Global Health and Medicine, Mr. Mitarai from Maruha Nichiro, and Mr. Nakanishi from Lipidome Labs. First of all, Dr. Shindo will introduce himself!

Shindo: My name is Shindo from the National Center for Global Health and Medicine. I specialize in lipid research. First of all, I would like you to know that there are good lipids and bad lipids, and that balance is important. Today, I would like to talk about "research on manipulation of biomembrane phospholipids, which has finally become possible.

Inoue: I'm curious about the "finally" part.

Shindo: That part is really "finally". The cells of our body are covered by a biological membrane. The reason why each type of cell has a different shape is because of the different composition of the biomembrane that covers it. Intracellular organelles and nuclei are also covered by membranes, each with a different composition of membrane. To zoom in, the biomembrane is a bilayer structure, the main component of which is phospholipids. Phospholipids are composed of hydrophilic heads and hydrophobic fatty acids, and there are more than 1,000 types of phospholipids in our bodies.

Shindo: Can you imagine the ratio of cell size to membrane thickness? If a cell is a ball one meter in diameter, the thickness of the membrane is only one millimeter. The actual size of a cell is about 10 to 50 micrometers (one micrometer is one millionth of a meter), and the thickness of the membrane is only about 10 nanometers (one nanometer is one billionth of a meter). In other words, they are very thin.

Inoue: You mean very thin.

Shindo: Yes, it is very thin. Various fatty acids are the building blocks of this very thin film.among (other things)Fatty acids called omega-3 and omega-6 are essential fatty acids that we cannot make in our bodies. These must be obtained from the diet. There are also saturated fatty acids and other fatty acids that can be synthesized in the body. The combination of these various fatty acids produces membranes with different functions. However, the mechanism of how each fatty acid regulates biological functions is still largely unknown.

Diversity of lipids that shape the body and new research possibilities

Shindo: There are diverse types of phospholipids, and their composition varies depending on the tissue, cell, and even the location within the cell. This is the same as our clothing, which changes material and shape according to its use. Cells and cell organelles are similarly optimized in their membrane composition according to their function.

Shindo: The reason I say "finally" is that the concept of phospholipids was proposed in the 1950s, but the responsible genes were not identified until around 2000, and we had to wait until around 2020 to identify the current number of genes. We have discovered several genes, but the ability to create genetically engineered mice (mice in which specific genes have been manipulated) has made it possible for the first time to experimentally manipulate phospholipids in vivo. This made it possible to conduct comparative experiments with normal mice.

Shindo: For example, when the production of phospholipids including arachidonic acid decreases, dietary lipids accumulate in the cells of the small intestine, making it impossible to transport nutrients into the body; when phospholipids including docosahexaenoic acid (DHA) cannot be produced, abnormal sperm morphology and visual function can occur. This is one of the reasons DHA is good for the eyes. Although there is still much to be elucidated, the importance of DHA is clear.

Inoue: So this study is relatively new?

Shindo: The phospholipids that all cells have acquired diversity during evolution. Or perhaps life evolved because of the diversity it acquired. Lipids influence all life phenomena and are involved in many diseases. Therefore, we believe that they may be potential targets for the development of new diagnostic and therapeutic methods.

Inoue: So lipid research is just the beginning. Now is the time!

Shindo: This is a real opportunity. There will be many discoveries to come.

Inoue: Let's hear from Mr. Mitarai of Maruha Nichiro about the important omega-3 as a food mentioned by Dr. Shindo.

Mitarai: I am Mitarai of Maruha Nichiro. DHA is good for the eyes and brain, and is expected to improve cognitive function and memory. We conducted a clinical study to confirm its effectiveness.

Mitarai: We conducted a study with the cooperation of Shimane University in a community with a large elderly population on the border of Shimane and Hiroshima prefectures. Residents were asked to consume Risaara sausage daily for 6 months, and cognitive function tests were conducted periodically. As a result, data showed that scores improved after 3 and 6 months compared to the beginning of consumption. This result was statistically significant, and the Consumer Affairs Agency granted the product a Food with Functional Labeling "Supports Cognitive FunctionThis was one of the evidences of the

Mitarai: In addition to "Green Risaara," which is effective in lowering neutral fat, the Risaara series also includes "Blue Risaara," a low-sodium type, and "Red Risaara" (food for specified health uses), which is designed for heart and blood vessel health.We are developing a product lineup that helps maintain a healthy cardiovascular system.

Inoue: Next, let's talk to Mr. Nakanishi of Lipidome Labs, an expert in lipid analysis.

Nakanishi: I am proud to say that I am the biggest "oil lover" of them all. I have been engaged in lipid research for many years. Originally, under the guidance of Dr. Shindo, I studied the important structures of biological membranes. The research methods used at that time did not capture the diversity and comprehensiveness of lipids, and we only investigated the one-to-one relationship between individual lipids and phenomena. I felt that this was not the way to achieve a true understanding.

Nakanishi: In order to analyze lipids comprehensively, we focused on mass spectrometry (a method to measure the mass of a substance with high precision). At the time, however, the technology and equipment were inadequate, and "lipids could be measured, but the overall picture was unknown. Therefore, I started by developing the technology and equipment myself, which led to the current Lipidome Lab.

Oil Lovers" Talk about the Evolution of Lipids and Their Role on the Planet

Nakanishi: Lipids have existed for about 4 billion years since life began on Earth. Lipids were essential to the cell membranes of the first unicellular organisms. During the course of evolution, lipids have acquired diversity and function. Modern humans synthesize lipids in their bodies, but most of them are obtained from food. The body metabolizes the lipids it takes in and converts them into lipids with different functions, or uses special lipids derived from plants.

Nakanishi: Currently, there are about 50,000 types of lipids registered in international databases. Theoretically, however, it is said that several million types exist. There is a vast number of lipids that we have not yet grasped. Even for the 50,000 lipid species that have been identified, although their structures are known, their functions are still largely unknown. We believe that it is our mission to explore this uncharted territory.Our vision at Lippidome Lab is to "create a society where the value of Lippidome changes the value of things.

Inoue: Let me share some general information about the importance of lipids. It is said that the human body is composed of about 60% water and 18% protein, but there is as much lipid as protein, and some people have more lipid than others. Although lipids are an important component of one's body, their analysis is not yet fully developed.

Inoue: Lipids as nutrients are also important. It is one of the five macronutrients, but unlike protein and vitamins, we may not consciously consume it.

Inoue.: Should I cut back on fatty foods like stewed cubes from now on?

direction: The type and balance of fats is important. It is important to consume fish oil, especially omega-3 fatty acids, rather than cubes.

directionThere are several reasons why we can't live without oil: it's a source of energy, it's a source of protein, and it's a source of protein. In addition to being a source of energy, oil plays a variety of roles, including being a source of hormones, a component of cell membranes, and assisting in the absorption of fat-soluble vitamins. While some believe that "oil should be avoided," essential fatty acids such as omega-3 and omega-6 cannot be synthesized by the body and must be obtained from the diet. However, overall balance is important.

Inoue: Regarding the current status of lipidomics, according to RIKEN data, lipids are classified into eight categories and about 20,000 species have been identified. Including predicted structures, there are more than 40,000 species, but according to Nakanishi, there may actually be from 100,000 to more than 1 million species. In other words, there is still far more that we do not know about lipids.

The Future of Lipidomics and "Sashimi is the Heart of Japan

Inoue: I would like to ask Mr. Nakanishi, one of the leading experts in Japan, about the current status of lipid analysis.

Nakanishi：We perform lipid analysis on 4,000 to 5,000 samples per year. Many of our analyses are food-related and microorganism-related. Lipid research has a full-fledged history of about 60 to 70 years. In the beginning, the focus was on industrial oleochemistry, but gradually nutritional and life science approaches have increased.

Nakanishi: Current lipid analysis utilizes mass spectrometry technology to obtain higher resolution and more detailed information. It is now possible to observe lipids more precisely, just like increasing the magnification of a microscope. For example, it has long been said that lipids are important for the brain and skin, but now it is possible to identify which lipid molecules are particularly important at the molecular level.

Inoue: So far, you have only studied the relationship between specific lipids and phenomena individually.

Nakanishi：Yes. For example, in genome research, initially only the presence or absence of specific genes was examined, but with the development of genomics, it has become possible to comprehensively analyze all genes at once. Lipid research has undergone a similar evolution, and it is now possible to analyze a variety of lipids in cells at once as lipidomics.

Inoue: If a medical researcher wants an exhaustive lipid analysis, how should he/she request it?

Nakanishi：Basically, if you send us your cell and tissue samples as they are, we will perform appropriate pretreatment and analysis. If you want to examine the relationship between lipids and a specific physiological phenomenon such as an immune response, it is more effective if you provide us with samples from control and treated groups. If we find lipid differences, we can perform a more detailed analysis.

Inoue: What kind of lipid regulation of biological functions do you have in mind, and what do you think are the results that can be achieved by further lipid research, Dr. Shindo?

Shindo: A clear example of the biological effects of lipids is prostaglandins, which induce fever and pain. Analgesics such as aspirin and loxonin inhibit the production of these. In addition, the results of lipid research are already contributing to medicine and health maintenance, such as cholesterol-lowering drugs and functional foods containing EPA and DHA. Further progress in elucidating the functions of cell membranes may lead to completely new approaches to drug discovery. It will also deepen our understanding of disease mechanisms and life phenomena that have not yet been elucidated.

Inoue: Mr. Mitarai, as a company, you are focusing on functional lipids such as EPA and DHA. If new functions of new lipids are discovered, is there a possibility that this could lead to product development?

Mitarai: Of course there are. However, it is important to make the right choice because some fats are good for the body and some are bad for it. Also, good lipids are not something that can be consumed once and have an immediate effect; it is important to accumulate them in the body through continuous intake. The presence of lipids in food and their absorption efficiency are also important factors.

Inoue: How do DHA and EPA work in the body?

directionDHA/EPA: DHA/EPA is taken directly into the body and incorporated into cell membranes, etc., where it functions. Although DHA and EPA are eventually metabolized, their concentration can be maintained at a certain level through continuous intake.

Inoue: So that's why fish consumption is recommended.

directionThat's right. Fresh fish, especially sashimi, is recommended.

Inoue: "Japanese heart, sashimi is very good!" That's what I mean.

Nakanishi：Unlike other lipids, there are few reports of side effects from excessive intake of EPA and DHA. However, they are not completely harmless, and a good balance is important.

The Future of Lipid Research and the Road to Social Implementation

Inoue: What is the view of each expert on the future of lipid research? Mr. Mitarai, do you see any possibility for EPA/DHA to be marketed in forms other than sausages?

Mitarai: One of our eternal themes is to research the application of DHA to foods other than sausages. Beverages are one promising target.

Inoue: So the time for taking DHA as a beverage is approaching.

Mitarai: The issue is the fish smell of DHA and we need technology to control this. If anyone has technology in this area, please contact us.

Inoue: Mr. Nakanishi, what do you think about the future of lipid research?

Nakanishi: Compared to protein and genome research, lipid research still has a short history and many unexplored areas. I see potential for lipid research not only in human health, but also in a wide range of fields such as food, plants, and microorganisms. These fields are still largely unexplored, and I believe it is time to actively promote research in these areas using current technologies.

Inoue: Mr. Mitarai, what is the future outlook for Maruha Nichiro?

Mitarai: As a fishery company, we want to deliver the value of the health functions of fish, especially functional ingredients such as DHA, more widely to society. We will continue to contribute to a healthy society by offering our products in a form that is easy to consume.

Inoue: Dr. Shindo, from an academic perspective, how do you see lipid research developing in the future?

Shindo: Lipid research is now in a period of opportunity. However, there are limitations to lipid research alone, and it is important to interact and collaborate with different fields. By intermingling various fields with lipids at the core, we can expect an explosive development of research.

Inoue: Thank you very much. Lipidomics is a field that will develop in earnest in the future. Those who are considering lipid analysis can consult with Mr. Nakanishi, conduct joint research with Dr. Shindo on the target lipids discovered, and then collaborate with Maruha Nichiro to link the results to the development of Maruha Nichiro products. Thank you very much for your time today.