Fat or sugar? Genes may decide for you

10 October 2016

Interview with

Professor Sadaf Farooqi, University of Cambridge

Given a choice, which would you prefer: a creamy korma, or a sugary eton Korma Currymess? Your genes may well be making your mind up for you: a new study out in Nature Communications this week has shown for the first time a direct link between our DNA makeup and our food preferences. Naked Scientist Graihagh Jackson went to chew the fat with the author of the study, from Cambridge University, Sadaf Farooqi...

Sadaf - Well really what we're interested in doing is trying to work out why some people gain weight much more easily than others. And we know that whilst for all of us the amount of food we eat, and the amount of activity that we undertake are really important, some people gain weight much more easily than others and find it very hard to lose weight and, for those people, genes play a major role in their weight problem. And so what we been doing for many years really is trying to find some of those genes and work out what they're doing and here we were focused on one particular gene called MC4R.

Graihagh - And what does that gene do?

Sadaf - Well we know from quite a lot of work, including work that's been done in mice, that that gene is key to regulating weight and it does so by affecting appetite. And here what we were looking is whether the gene also might affect food preference: which foods you choose.

The challenge of course is humans are not mice and we needed to find a way to test food preference using regular meals. And, so what we did, we did lots of tests ourselves, and I personally volunteered to try all of the food, and what we did was we found that chicken korma and rice was a really useful food to use. And the reason it's useful is we could make a chicken korma and rice that was twenty per cent fat, forty percent fat, and sixty per cent fat. The key thing really we wanted to do here is you need to make sure they look exactly the same and they taste the same.

So the study involved normal weight people, people who are overweight but have a normal MC4 gene, and people who are overweight but have a faulty MC4 gene. And what we found is that when we asked everybody just to do a little taste test and try out the three types of chicken korma, they couldn't tell them apart. But then, when we left them in a room with a large tray, a buffet style approach, we found that the people with the MC4R gene that was defective ate ninety-five percent more of the high fat food than the normal weight controls, and they eat sixty-five percent more than the obese controls. So really a very marked food preference.

Now what was interesting was the total amount they ate at that meal was exactly the same in all three groups. So it's not that people necessarily ate more, but they switched their preference towards high fat.

So what we thought originally is that they may be both fat and sucrose preference in these folks because both things will give you plenty of calories. Interestingly, while we were doing the study on sucrose preference, mouse data came out suggesting that mice have less of a preference for sucrose, they don't like sugar.

So we set out to test that out in people as well. Originally we tried yogurt; that didn't work very well because nobody really like the sweetened fruit yoghurt, so we ended up with Eton Mess. And what we found is that the lean people; the obese people do what most people would do is that they like the sweeter things but, actually, the patients with the MC4R defect actually really didn't like the high sucrose Eton Mess. In fact, they hardly ate any of the Eton Messes that we gave.

So it suggests really that we have a pathway in the brain that can pick up the fat content in the food, even when we don't realise.

Graihagh - That's really intriguing because you would have thought, evolutionary speaking, you want to put on as much weight as you can for those feasts and famines, so why would you choose fat over sugar?

Sadaf - I think the possible explanation, but we would have to test it, is that this pathway is there to defend us against starvation. So, in people where the MC4R gene is defective, effectively that pathway's on the whole time; their brains and their behaviour is like as if they're starving; they need food. So I think it would make a lot of sense is that if you're starving you want to get more fat because fat has twice as many calories per gram as carbohydrate or protein. So that bit, I think, makes quite a lot of sense.

The bit that was confusing is the sucrose because, surely, that's got calories in it. Why wouldn't you eat sucrose? But then actually, what we thought about is that if you eat quite a lot of sucrose, you can only store a certain amount in the liver and actually, after that, it's waste. Whereas fat, of course, you can keep storing in your fat tissue so it would make a lot of sense that if you're starving, the thing you need to is fat and, actually, you need to make sure that you don't waste time eating sucrose because you can't store very much of it, whereas you can store the fat.

Graihagh - As many of us I'm sure know, myself included.

Sadaf - Exactly. And I think this is what's interesting is that whilst this finding came from studying a relatively rare group of people who have this gene problem, actually its relevance is much broader because we all have this pathway. And it's part of understanding really that you know what, our biology will influence our behaviour.

Graihagh - Does that mean, in some way, we're powerless, we're predetermined to always want to put on weight or does this mean we can perhaps harness this and work with it a bit?

Sadaf - So, of course, I often get asked that question.  And I think the main thing is the assumption that something like eating and eating behaviour is purely down to free will is something that is challenged by this research. I think this research, and the work that's been done in animal models before this clearly shows that biology has an important part to play. But, of course, human beings are complex creatures and we work with our environment so there are potentially ways of modulating, or controlling, or influencing this behaviour, so I don't really think it's deterministic but I think it's important to recognise there's a biological component too.

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