 Hei. It really is a privilege to get to present my research to a public audience, so I'm very grateful that you're all there and I have this opportunity. What I'm going to do is tell you first a little bit about omega-3 fats, then a little bit about how obesity leads to disease, and then I'll take you through some of the work that I've done during my PhD. So omega-3 fats, they're a type of unsaturated fat that our bodies cannot make. We have to consume them if we want to increase the amount to our bodies. And they have effects on the body that are different to the other unsaturated fats or the saturated ones. The main sources of omega-3 are from the sea, and fish, crow and algae are the main sources, and you can get them from eating those or from oils made from them. However, these molecules are also highly reactive, which means that they go off or oxidise very easily during storage. The main reason that people take omega-3s are either to prevent heart attacks, prevent cardiovascular disease, or during pregnancy they're often taking with the hope of improving the intelligence of the child. And it would have to be said that in the last 10 years, both of these have really not been born out in most of the studies. Nevertheless, there's still the main reason people take them, and they're taken by a lot of people—about 17% of Americans in one study and 20% of pregnant women in New Zealand. Now, everyone will be well aware that obesity is a massive problem for us. It's a global problem. There are now 500 million obese people in the world, and New Zealand has a big problem with this as well. More than half of the population is now either overweight or obese. The reason this is important is because obesity leads to higher blood pressure, higher cholesterol, and the development of diabetes, and together these lead to cardiovascular disease, which are the biggest killer in this country. Importantly, the underlying problem that's linking obesity to these problems is that insulin, the hormone that controls your blood sugar, doesn't work as well if you're overweight or obese. A very special group that we should think about as well is women who are pregnant. We know that the offspring of women who are obese while they're pregnant are more likely to become obese themselves and have a higher rate of diabetes and metabolic problems as they age. And this, too, is probably because insulin's not working very well in mum. That leads to her to have higher blood sugars and fats that cross the placenta and have long-term effects on the baby. So, this raises the possibility that insulin-sensitising treatment, when it makes insulin work better, could have a dramatic impact on these populations. Now, could omega-3 fats be this treatment? Well, in mice and rats, treatment with omega-3 fats does restore insulin function. So, that's what we got excited about and why we've done the research that I'm going to describe. We've had four really important research questions. The first is that could omega-3 supplements improve how insulin works and people who are overweight are obese? Second is, if we gave omega-3 fats to obese mothers, could we improve the health of their offspring as they age? We also wanted to know, are omega-3 supplements offered at the time they're purchased by consumers and does that make a difference to how they work? So, please follow me down the wrapped hole that was my thesis. So, first, are these supplements oxidised when you buy them? The short answer to that is yes. I surveyed most of the omega-3 products on the NZ market and I measured how oxidised they were using a standard test. And this dotted line represents the recommended level of oxidation. You can see that almost every product exceeded that and some by a large degree. Now, what does that mean for people taking them? We're not sure. That dotted line is actually the dotted line for whether the oil tastes bad or not, not for whether it changes its function. So, it's a really important question to ask, given that everyone is taking oxidised oil. The next question is, could we use an omega-3 supplement to improve how insulin works and people who are overweight or obese? To find this out, we enrolled overweight middle-aged men into a trial and we randomised them to receive one of two treatments, a krill-based omega-3 supplement, which is a small crustacean fished up in the sea, or a controlled oil. And they took the supplement for eight weeks, we assessed their metabolism before and afterwards and then they had a break and took the other supplement. So, they didn't know what they were taking at each time, but every person got both supplements. And it's worth pointing out that neither of the oils we used were oxidised. That can't explain our findings. So, the first thing we found was that at the start of the trial, before anyone had taken any krill oil, those who had more omega-3 in their blood, insulin worked far better in their bodies. Those with the lowest level, insulin wasn't working very well and it was quite a big difference. So, that so far so good. However, when we gave them krill oil, we actually found that their insulin seems to be got worse. Insulin wasn't working as well as it was before we gave the krill oil. And it's actually quite a large effect. This suggests that if these men took this for years, it might have increased their risk of diabetes or cardiovascular disease. How did this happen? Why? We don't actually know. It's probably not due to the omega-3 fats in the krill. We think it's probably another compound that's unique to krill and probably not found in fish. Supporting that, a recent study from Europe has shown that giving a purified omega-3 supplement improvements on action and reduced the development of diabetes in adults. So, it looks like omega-3 probably is good for metabolism, but that krill is not the way to get it. The next question we had was, could we use fish oil in the offspring of obese mothers to prevent them developing metabolic disease? Now, to first test of this, we had to do it in animals. And the reason for that is because if we do an infection in mothers and have to wait for their children to grow up to be assessed, that takes years and years. And so, the first study was done in rats. What we did was we assigned some pregnant, sorry, some female rats to a normal diet and some to a high-fat diet. We know that a high-fat diet in pregnancy is similar to an obese pregnancy in that the offspring still become obese and they get problems with how insulin works. And so, the rats took those diets after we mated they continued on them and then we gave them an extra treatment, which was either fish oil or water, which was our control. And what we're aiming to do is see if, by giving that fish oil to the high-fat groups, we could prevent this problem with insulin action. Once the offspring were born, they fed an ordinary diet for their whole lives as much as they wanted to eat and we assessed them in adulthood. So the only thing we did was change what mum had during pregnancy. We also added one more group, which makes it look much more complicated. And what we did here was we took some of our very fresh fish oil and we oxidised it so that we had an oil that was identical, except that it was oxidised. So what happened when we did this? Well, the first thing was dramatic and completely unexpected. Once the pup started to get born and the group whose mother had had oxidised fish oil, we saw an incredible rate of death. Almost a third of those pups died very soon after being born. But it didn't happen in the fresh fish oil group, which tells us it was the fact that it was oxidised that mattered. And we don't know quite why that happened. We didn't expect it so he didn't do the right tests to find that out. Those that survived were often different to other animals as well and so this little guy, next to a rat from a different group, is about a third the size and he didn't move normally either. That's where I'll stop talking about the oxidised groups. This was featured in the listener earlier in the year as well and quite an in-depth article. But what happened to the other animals? What this graph shows is how they gained weight from early life through to adulthood and high-fat diet means that mum had the high-fat diet. Remember that offspring have had exactly the same thing. Now this finding isn't new but it kind of blows my mind. I think this is amazing. By changing mum's nutrition in this very small window, we've had a permanent effect on their self-spring. That's amazing. Now, what happened when we added fish oil to this? In terms of weight, nothing. The high-fat diet groups still became obese. But there was one very important difference and that was an insulin action. So what you can see on this graph is if mum had an ordinary diet, the offspring are nice and insulin sensitive. If mum had a high-fat diet, they are much less sensitive. It's a big effect. But if we added fish oil to that, we completely prevented that and so we had obese animals that were more metabolically well. And that would still be an outcome that would be very favourable if it could carry through to humans. Now, what is a response to this quite shocking effect of the oxidised oil? The dose we used was high and it was more oxidised than what's on the market. And it's clear that women taking fish oil in pregnancy are not having a look their babies die. But if there were more subtle effects on things like growth, we might not know about that because it's not being looked at. Our approach to this now is to say, look, there is no compelling reason for women to take fish oil in pregnancy and we know if they buy it, it will probably be oxidised. So women who are pregnant probably shouldn't take fish oil and should get their omega-3 from fish. Saying that women who have been taking fish oil have probably not done their babies harm. And where to from here is two studies which we're designing and looking for funding for. The first is a careful study in rat pregnancy using doses of oxidised fish oil that are relevant to women to try to better estimate the risk of a woman taking fish oil. And we're working with the Ministry of Prime Industries and a toxicologist to design the sort of study the Government would listen to. The second thing is a human trial of using a very fresh fish oil during the pregnancy of women who are obese to see if we really can affect the health of their children as they grow up. And if we can do this, I'm going to be very busy. So I've made it sound like all my work was solely my own and of course it was into tax of village of people assisting. And I'm very grateful to those people. Thank you.