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Genetic Target May Prevent Weight Gain on High Sugar Diet

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Lisa Winter

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2346 Genetic Target May Prevent Weight Gain on High Sugar Diet

The average American now consumes about 26 times more sugar a year than Americans did 200 years ago. That's easy to believe with 69% of the adult population now overweight or obese. Researchers may have found a way to break the connection by targeting a gene that prevents weight gain under a high-sugar diet. The research was led by Sean Curran of the University of Southern California and the results were published in Nature Communications

The study was performed using human cells in vitro along with Caenorhabditis elegans, a worm that has been used as a model organism in genetic testing for decades. The gene in question is known as SKN-1 in C. elegans, while the human homolog is known as Nrf2. It is a transcription factor for antioxidant enzymes, which protect the cells against oxidative stress from a variety of diseases. 


Previous research with C. elegans has revealed that individuals with a mutation that causes SKN-1 to become hyperactive did not gain weight when given a high-sugar diet, while worms without it gained a considerable amount of weight.

“The high-sugar diet that the bacteria ate was the equivalent of a human eating the Western diet,” Curran said in a press release. A stereotypical “Western diet” consists of high levels of carbohydrates including sugar, meat, fat, and not enough fresh vegetables. 

The gene has been targeted for years due to its ability to boost antioxidant properties. Not only could it reduce the effects of aging, but it has also been sought to treat diseases caused by oxidative stress including multiple sclerosis (MS), Parkinson’s disease, Alzheimer’s disease, and kidney disease. This recent study found that the gene not only turns on factors that metabolize proline, an amino acid which can contribute to oxidative stress, but it also contributes to fat metabolization as well. 

While it might sound tempting to just try to crank Nrf2 up as high as it can go, the body regulates its expression for a reason. If over-expressed at too high of levels, it can contribute to aggressive types of cancer that do not respond to chemotherapy. As with everything in life, moderation is key.


“Perhaps it is a matter of timing and location,” Curran continued. “If we can acutely activate Nrf2 in specific tissues when needed then maybe we can take advantage of its potential benefits.”

Even though the study utilized human cells in a dish, don’t expect to see Nrf2 activators sold as a diet supplement anytime soon. The researchers plan on continuing to study this genetic target by attempting to activate it in mice, progressing through more complex organisms that could better predict how the drug would act while in the human body.

Of course, gaining weight isn’t the only result of chronically high blood sugar, so even if this drug is eventually approved for human use, it won’t be a blank check to eat Willy Wonka out of house and home. Hyperglycemia has been associated with diabetes, irregular heartbeat, blurred vision, and decreased ability to heal wounds or fight infections, which could have potentially fatal results.


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