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These Mutant Worms Hide the Secret to Gorging on Sugar Without Getting Fat

Researchers have discovered a genetic pathway responsible for converting sugar into fat.
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Sugar makes us fat, especially when it's over consumed—science tells us it is so. But what if it just didn't?

In the future, that could be a real possibility: Scientists have discovered a gene that apparently controls sugar's conversion into stored fat, and are actively working on devising drugs that could allow us to load up on the stuff without gaining any weight.

In a new study published in Nature Communications, Sean Curran and a team of researchers at the University of Southern California describe mutant nematodes that, even when fed diets insanely high in sugar, don't gain any weight.

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these mutants seem to be blind to the fact that they are eating the excess sugar

Yeah, OK—we aren't nematodes. But the gene, called skn-1, has an analogue in humans, and early experiments on human cells have shown the same findings. The research is being done with the specific purpose of finding a cure for obesity—or at the very least, of figuring out why sugar seems to rapidly build up fat deposits in some people, while seemingly having little effect in others.

In his experiment, Curran took both genetically-modified nematodes (C. elegans, a popular research organism) and normal, wild nematodes. He fed them both a normal diet, then switched both groups to a high glucose one. Even a small glucose increase had a major effect on the wild nematodes:

"We found that addition of 2 percent glucose to the standard diet could significantly induce a 250 percent increase in stored intestinal fat in wild-type C. elegans, as compared with worms feeding on a normal diet," Curran wrote in the study.

"Strikingly, when skn-1 gain-of-function mutants were fed the [high sugar] diet, they did not manifest this increased lipid phenotype," he continued.

In other words, "these mutants seem to be blind to the fact that they are eating the excess sugar," Curran told me in an email.

What now? Well, as I mentioned, this genetic pathway seems to be roughly identical in humans, with one main problem. The human analogue is called Nrf2, a gene that has also been associated with many types of cancer. So, targeting the expression of that gene with new drugs could, potentially, allow humans to be "blind" to high sugar diets as well. But it could also have unintended side effects.

That's all down the line, but research into that line of thinking is not as far off as you might think: Curran said that big pharma companies already know how to target that specific gene (for other reasons), and that future research is going to focus on how this initial finding can be used to fight obesity.

"We have targeted this pathway in human cells and it works in a manner similar to the worm," he told me. "We are exploring the possibility of using small molecules and drugs to target the pathway and see if we get the same change."