These days it seems that we are always hearing about the latest ‘wonder pill’ that will help you to get fit - often with very little science to back it up. Well, this time things are a little different. Scientists at the Salk Institute in California have discovered a new pathway used by the body during exercise and are able to recreate its effects in mice by simply giving them a pill. The mice were able to run for a much longer period of time and gained less weight! Tom Crawford spoke to senior researcher Weiwei Fan to find out how it all works.
Weiwei - This involves a protein called PPL-delta. So it is a lipid sensor and exercise activates this protein and this turns up genes that burn lipids, and turn down genes that burn sugar for energy that your muscle needs.
Tom - So basically, when we exercise this protein is activated and it causes the muscles to burn fat instead of sugar?
Weiwei - Exactly. So that’s why we think this is really interesting because previously people thought that turning up the genes in lipid burning is more important, but now we’re showing the glucose is the limiting factor in endurance determination.
Tom - I guess the next question then is if you’ve identified this protein which switches from burning sugar or using glucose to instead burning fat, then can we make this more active and would that give a boost to endurance?
Weiwei - Exactly. Yeah, that’s what we showed in the study. When we gave mice this drug called GW1516, this is a chemical that activates PPL-delta. So the mice that had this drug for 8 weeks, when we test their endurance capacity, they can run for about 270 minutes. The control mice, the mice that were not on this drug, they could only run about 160 minutes. And the increase was about 70%, and that’s huge.
Tom - With the idea here being to increase fat burning in the muscle instead of glucose, then surely this should also, for example, result in weight loss?
Weiwei - Yes. I think this drug will give enormous health benefits and something we can think about is obesity, type 2 diabetes, and fatty liver disease.
Tom - Did you actually see any changes in the weight of the mice?
Weiwei - Actually yes. These mice: we call them normal diet, so this is just where the diet was normal amount of lipid and sugar. When we give the mice a normal diet they slightly lost some weight and the weight loss was mostly on fat. But when we gave these mice a high-fat diet the change is enormous. When we compare the mice on high fat and with the drug to mice on high fat without the drug, we saw a 50% reduction on weight gain, so that’s huge. And the good thing is it mostly happened on fat mass so the muscle mass doesn’t change, but the mice they just had less fat.
Tom - Are you planning to hopefully try this out in humans? If you could say to somebody I can give you a pill and you will reduce your weight or something by 50% - that’s incredible.
Weiwei - Yeah. So I think that’s our ultimate goal is to apply our finding in humans. Right now this drug is not allowed to be used in humans because it has some really bad side effects. But our lab is developing what we call the next generation PPL-delta activator. Now we have some prototype that can give the same benefits - increasing endurance and fat loss. We are pretty sure that this new drug has very limited side effects are we are hoping that this PPL-delta activator can be tested in humans soon.
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