Dr. Jing Kang – How the Fat-1 Mouse Creates Omega-3 from Omega-6
OmegaMatters: Episode 13
Hosts: Drs. Bill Harris & Kristina Harris Jackson
Guest: Dr. Jing Kang, Associate Professor in the Department of Medicine at Harvard & Director of the Laboratory for Lipid Medicine and Technology at Mass General Hospital
Background and Key Takeaways: Dr. Jing Kang is an associate professor in the Department of Medicine at Harvard University and he’s also the director of the Laboratory for Lipid Medicine and Technology at Mass General Hospital. He received his MD degree in China and then got his PhD at the University of Alberta. He then went on to do post-doctoral work with Alex Leaf at Harvard University where he remains to this day. Several years ago, Dr. Kang created Fat-1 transgenic mice, which are capable of producing omega-3 fatty acids from omega-6 fatty acids, leading to abundant omega-3 fatty acids with reduced levels of omega-6 fatty acids in their organs and tissues, and without the need of getting omega-3 from the diet. In this episode, Dr. Kang talks about the implications of using Fat-1 technology in both research studies and to increase the fatty acid content of the food supply naturally.
Visit www.omegaquant.com/omegamatters-broadcasts/ to learn more.
Kristina Harris Jackson: All right. Hello, everyone. Welcome back to another episode of omega Matters, where we talk all things omega-3s. I’m Kristina, and with me here is Bill Harris, who will be introducing our guest for today.
Bill Harris: Yeah. Thank you, Tina. I’m really happy today to have Dr. Jing Kang with us from Boston. He’s apparently got a snow day there today so he gets to be at home, working. Jing got his MD degree in China and then got a PhD at the University of Alberta, and then went on to do post-doctoral work with Alex Leaf at Harvard University where he remains to this day. Now an associate professor in the Department of Medicine at Harvard, he’s also the director of the Laboratory for Lipid Medicine and Technology at Mass General Hospital.
Bill Harris: Almost 30 years ago, he published his first omega-3 paper. And that was with Dr. Leaf on cardiac cell membrane biology and omega-3 effects. Since then he has published 150 papers on omega-3 specifically.
Bill Harris: We wanted to have him here because he was the inventor and he’s been the father of one of the most novel research tools in the omega-3 toolbox — butt it’s not a tool, it’s an animal, which is, kind of, a weird thing. But we’ll let him tell you all about it. So, Jing, thank you for joining us and welcome.
Dr. Jing Kang: Thank you. Thank you for having me. I can’t believe I’ve been at Harvard almost 30 years.
Bill Harris: Well, that’s great. Let me just start out by asking you to tell us all about the Fat-1 transgenic mouse. What is that?
Dr. Jing Kang: Most mammals such as poultry and livestock and even fish cannot synthesize omega-3 fatty acid de novo, the whole molecules. The must get it from food.
Kristina Jackson: Mm-hmm (affirmative).
Dr. Jing Kang: So we created a technology to get animals to produce omega-3 without getting it from food. That’s the technology — an animal capable of producing omega-3 fatty acids from omega-6 fatty acids. So when we talk about the transgenic fat-1 mouse model, that’s only part of this technology. We can create a cell, a mammalian cell, so these animals are able to produce the omega-3 fatty acids without getting it from the diet.
Dr. Jing Kang: The technology is based on a gene called fat-1, which comes from C. elegans. We transport this gene into a mammalian cell or a whole animal and they can produce omega-3 fatty acid by converting omega-6 into omega-3. There are many fantastic things you can do if you change the level for omega-3 fatty acid at the cellular level, in the tissue, in whole, in the organ, in the whole body.
Bill Harris: So, what’s the advantage in creating a genetic model that makes its own omega-3 versus just feeding the animal omega-3?
Dr. Jing Kang: Okay. That’s a good question. We want to solve important problems. We know omega-3 can come from marine products, like seafood and some micro algae, which are the current main sources of omega-3 fatty acids.
Dr. Jing Kang: So with this technology we can create omega-3 in land fed animals without having to rely on any marine resources. This means we can still enjoy the food we like to eat — steak, eggs, bacon — but now with lot of omega-3 fatty acids in there. For humans, this means they won’t have to change their lifestyle or eating habits.
Dr. Jing Kang: And this is not just about the convenience — this technology is also good for human health and the environment. Our technology ultimately solves the issue of omega-3 availability.
Dr. Jing Kang: The Fat-1 mouse model can overcome a few very important problems we encounter every day in the lab. Everyone working in this field know very well that in order to modify the fatty acid composition in animal tissue, we have to use a different diet or different fatty acid composition. For example, we create a higher omega-3 fatty acid or a low omega-3, and we can compare these two different fatty acid compositions to see which one is better for health. But there are many confounding factors through this process. This is the main problem for nutritional studies, especially when using omega-3 fatty acids, because they are so unstable. This is why these studies can be so inconsistent and sometimes conflicting.
Dr. Jing Kang: So, I think that’s a big issue for a feeding study. So, with the availability of a Fat-1 mouse model, because the Fat-1 mouse can convert the omega-6 to omega-3, now we can use that synchronized to feed the two group of animals. They all eat the same thing. But the consequence is the one group will have a higher omega-3 and one is lower.
Dr. Jing Kang: This is a nice system that allows us to see many things such as the lipid mediators and gene expression. We can answer a lot more questions in studies using this technology of gene transfer.
Dr. Jing Kang: So, that’s the first thing we can overcome with this technology are the confounding factors from the diet. That’s number one. More than that this allows us to examine fishes and ask many other questions. Normally, we cannot do that in the feeding study. For example, we can look at the development the user are mating strategically, allowed a mother can have a littermate, maybe for the Fat-1 or wild type in the same litter.
Dr. Jing Kang: So, after birth, they can follow, they come from the same mother, but one with the Fat-1 gene, one without, and eat the same thing, everything the same, identical. And then you can look at the offspring is in healthy condition and track the disease development, and the sensitivity to environmental factors.
Dr. Jing Kang: And we are also able to at something like the microbiota. We can use the microbiota intervention. We can just simply change the gut cells, the fatty acid profile without changing the diet. The diet is still the same for the two groups, but one group has the high omega-3 and the other one does not. And then you look at the microbiota in the animal. And that’s something we’re able to examine. Otherwise, if you feed different diets, you don’t know what’s causing the change.
Bill Harris: So, you’ve really got two big motivations, as I see it, one is to create a research model that avoids some of the problems of feeding studies and the other purpose was to provide a way to get “regular foods” for humans to have omega-3 naturally.
Dr. Jing Kang: Correct.
Bill Harris: Now, tell us what you’ve learned from the Fat-1 mouse, just a few of the highlights.
Dr. Jing Kang: First, thank you for your summary. The main two things is for the technology to produce omega-3 and the second to provide a model for the research. And I think, that’s quite important. This Fat-1 mouse model so far has more than 250 publications from the obesity to the longevity. The mouse model is being used in more than 20 countries by now. That is something I didn’t expect.
Bill Harris: That’s great.
Dr. Jing Kang: Many investigators use this model. Also, they can use that feeding study to side by side try to validate them. We can use the data to validate the study done before or they done now, whether it’s a feeding study. We can convince the mainstream that omega-3 is important. And they can do a lot of things there. That’s the point. So, I think that we already addressed many things. To simply change part for the omega-6 to omega-3, they bring the total amount. That’s another thing I want to emphasize here. The total amount of the PUFA — just omega-6, omega-3 is different.
Dr. Jing Kang: And then you can see a lot of conditions, from the obesity, fatty liver, to cancer, to mental diseases and the brain development, gut microbiota, and so many things change. That’s why I feel this so important, we hope that more people understand the importance of omega-3 for human health.
Bill Harris: Right. Right.
Dr. Jing Kang: We can see that what in the animal and then we can see what in the human.
Kristina Jackson: Yeah.
Dr. Jing Kang: So, we haven’t found so many thing that can be modified, that’s changing the omega-3 content or change of omega-6 formation. So, I think that that’s something I learned a lot about. First thing, that they affect many things. And the second, it is some fundamental thing, for example, decoding that information — that’s a very important thing.
Dr. Jing Kang: And almost every study to measure the cytokines and how their fat, the microbiota, this is relatively new, their fat, their lipogenesis. And I view these three things as fundamentally important for the development of a chronic disease.
Dr. Jing Kang: Now, omega-3 fatty acids can fundamentally, profoundly change a disease. And often these three things can be a factor. And so, the important thing is that many of those chronic disease — cancer and CVD, diabetes, and Alzheimer disease —they have the same pathology, or they relate to those three things I mentioned. So, omega-3 can change this thing, which is why many studies use the fat-1 mouse.
Bill Harris: Yeah.
Dr. Jing Kang: And we can use that at the genetic level for lipidomics, for metabolomics. I think this is exciting.
Bill Harris: I can see you’re excited!
Dr. Jing Kang: Yeah, no, there is this other thing that is going on there. That’s another nice thing you get closer, this fat-1 mouse model be for other disease, model, for example, cancer, cancer or Alzheimer’s disease, and many other disease, genetic, disease model.
Dr. Jing Kang: Then you can follow up from the beginning to the end, to see what is changed there.
Bill Harris: Yeah.
Dr. Jing Kang: And without it, we have to give the different diet where we end up putting confounding factors into the study.
Bill Harris: Can you achieve levels in humans equal to what you achieved with your mouse model?
Dr. Jing Kang: Oh, actually, you know, as I mentioned, there are many, many study that where they used the two approaches — the transgenome, mouse model, and also the feeding study. You can see the fatty acid level is very comparable. And even when they feed the different level of omega-3. You see how much the omega-3 you feed you can raise it to the level in the fat-1 mouse model.
Bill Harris: Okay.
Dr. Jing Kang: So, the study, they get the answer. I think one group in Korea, they published the paper already. They found that for by body weight, if like a human, like 60 kilogram, their body weight, if we, you get a one gram bread, you get the omega-3 fatty acid similar to that in the fat-1 mouse model.
Bill Harris: Oh, really?
Dr. Jing Kang: So, it’s more than one gram, but not… So, more than one gram, EPA, that, they, the purer, omega-3 fatty acid. And so, that’s very comparable.
Bill Harris: So, you’re saying that, roughly speaking, about one gram of EPA DHA per day for human would get you the levels that you see in your mice?
Dr. Jing Kang: Yes.
Bill Harris: What is that dose you get? ‘Cause as you said, you take omega-6 and convert it to omega-3 so you’re reducing the omega-6 at the same time.
Dr. Jing Kang: Yeah.
Bill Harris: Can you tell if the effects you’re seeing are due to the omega-3 going up or the omega-6 going down?
Dr. Jing Kang: Well, that’s another very important point, Bill. This model, they use omega-3 as the substrate and to produce omega-3. So, when the omega-3 up, omega-6 down. They adjust the level.
Kristina Jackson: Mm-hmm (affirmative).
Dr. Jing Kang: So, you know now, today many people have a too much omega-6, yeah. But we cannot reduce omega-6 this significantly. Okay? You ask them to eat more omega-3 to try to get their omega-3 level up. If they’re raised or changed, because it relies on how much omega-3 we eat.
Kristina Jackson: Okay.
Dr. Jing Kang: And that’s why sometimes if we just look at the omega-3 alone, the amount that they take, sometimes we can see the outcome, it’s a little bit different. So, what we learned from fat-1 mouse is that we can reduce the certain level for omega-6, that way, the fat-1 mouse you decrease that from inside.
Dr. Jing Kang (23:42): I think that we need to prove that in human if we do a study to validate that. But of course, we’re not all the same. It will depend on the omega-6. If someone already has a very high level for omega-6, if they do apply it, the life, what we’re talking about, maybe it’s more effective. If there’s somebody is already low, and maybe it’s not. So, I think depend- depending on what we need to check find out.
Bill Harris: Yeah, let me ask you one more question. Going back to what you talked about in changing the omega-3 composition of poultry and beef, and pork and, even fish, right?
Dr. Jing Kang: Yeah.
Bill Harris: Have any of those animals been commercialized or are they available in the marketplace?
Dr. Jing Kang: Ha, I actually, perhaps you should know about that.
Bill Harris: Regulatory.
Dr. Jing Kang: Better than a regulatory issue. You know, I can say this technology is really useful, helpful to the public health. And as I mentioned earlier, unlike many other, genetically modified animals, they can make the animal grow faster or many, or resisting to a disease, or something else, but our technology is just try to increase the nutritional value. It’s overcome a big problem that we are facing right now, the whole wide world, because we need these nutrients.
Bill Harris: Yeah.
Dr. Jing Kang: But we cannot just rely on the ocean or relies on the fish, that we can increase the omega-3 in different product lines.
Dr. Jing Kang: So, I think that something, even though we have a testing issue there, that I am so confident that this technology can help.
Bill Harris: Yeah, yeah.
Dr. Jing Kang: I hope that it can come to the market.
Bill Harris: Great.
Dr. Jing Kang: Now it’s not, Bill. It’s not.
Bill Harris: Not yet. Ok.
Bill Harris: But I think we need to wrap up our talk today. We want to thank you for taking the time.
Bill Harris: …to share the Fat-1 mouse with people. I’m sure many of them never heard about it but it’s a fascinating development. Congratulations for thinking about this.
Dr. Jing Kang: Thank you, thank you.
Bill Harris: And, we wish you well as you continue with this work and we’ll stay in touch.
Dr. Jing Kang: Thank you. I enjoyed talking with you both and I look forward to more exciting studies from your group.
Bill Harris: Great. Thank you. So, we’ll be in touch, take care.
Dr. Jing Kang: Okay.
Bill Harris: Bye bye.
Kristina Jackson: Thank you so much.