Fat fish may help us lose weight

Over 60% of the UK population are classed as overweight or obese, which carries anincreased risk of many health conditions from diabetes to cancer. But it's not just humans that can get a little plump. By studying the genes of some chubby fish from Mexico, Harvard's Ariel Aspiras found our fat fishy friends were actually very healthy and suffered none of the ill effects that overweight humans do. What makes these fish so special? How do they get so fat yet stay healthy? And what can we learn from them when it comes to fighting the flab? Amy Goodfellow swam across the pond to find out more...

Ariel - I was really curious as to why some people can eat a lot of food and not gain weight, and why other people can eat very little food and gain a lot of weight. And so, these inherent differences in metabolism are not really well-understood. We were interested in looking for population differences, in metabolism between this species, the Mexican cavefish. There's a subset of the population that lives in the caves and then there's a surface population and they're both the same species. So, when we started this experiment, we thought this would be a great system.

Amy - These fish are the same species but the cavefish have evolved slightly differently. The cave dweller is a bit of a fatty compared to the surface counterpart. This makes them great to study because you can find out which genes cause which traits.

Ariel - We found a few metabolic differences. One of them was their starvation resistance - their ability to just lose less weight when they're fasting. Another is just their general adiposity - how fat they are in general. And then the third type was this hyperphagia phenotype or overeating. They kind of tend to binge eat relative to the surface fish.

Amy - The cavefish are fatter and have slower metabolisms, so don't lose weight as quickly as the surface fish. They also have this remarkable ability to binge eat - sounds pretty similar to me! But given they're the same species, why are they so different?

Ariel - It's because of their environment. Throughout the year, they're kind of starving for the most part and then one time of the year, when there's flooding and there's food getting washed in, there's a lot of food available. And so, they kind of just have to gorge on food. And so, they've evolved to take advantage of that by binge eating and not stopping when they're full. Whereas the surface fish, if they do that, they get a lot fatter and then they become more of a target with predators whereas these cavefish, they don't have any predators.

Amy - I have a great image in my mind of these really fat fish swimming around in these caves. But are these fish actually unhealthy because of this large amount of fat or do they cope well with this?

Ariel - In our lab, these fish are pretty healthy. They live for 10 years. So did the surface fish. We've looked at some blood parameters to test whether or not they have liver damage or other complications associated with being really fat and they appear to be fine.

Amy - What's key here is that these fish have one vital alteration in their genome - a gene called MC4R and guess what, this mutation is also found in humans.

Ariel - There's a lot of humans that have mutations in this gene and are obese. So, it's associated with obesity. And when you knockout this gene - so 'knockout' means takeaway or you don't have a copy of this gene. You get really, really fat and it happens not just in humans but in mice and other animals as well. And so, this is a really good candidate gene to explain some of the differences in this overeating phenotype we see.

Amy - Does your research have any applications for humans and obesity?

Ariel - With this particular gene, no. This is more of an initial pass at trying to identify genes that are involved. This is kind of a good proof of principle given that we identified this gene that's different between these two populations and this gene is also different in a lot of obese humans. It is promising though because it does tell us that we keep looking at these metabolic differences between this fish. We could potentially identify other genes that are novel that could be contributing to both their differences in fat content, but also to their difference in their ability to tolerate extreme differences in their adiposity.