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Fructose Alters Brain Genes, Can Lead to Disease

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Diseases ranging from diabetes to cardiovascular disease and from Alzheimer’s disease to attention deficit hyperactivity disorder are linked to changes to genes in the brain. A new study by scientists from UCLA life sciences and the school of medicine has found that hundreds of those genes can be damaged by fructose, a sugar that’s common in the Western diet, in a way that could lead to those diseases. However, the researchers also discovered good news: An omega-3 fatty acid known as docosahexaenoic acid, or DHA, seems to reverse the harmful changes produced by fructose.

“DHA changes not just one or two genes; it seems to push the entire gene pattern back to normal, which is remarkable,” says Xia Yang, PhD, assistant professor of integrative biology and physiology. Dr. Yang and Fernando Gomez-Pinilla, PhD, professor of neurosurgery and of integrative biology and physiology, are coauthors of the study.

To test the effects of fructose and DHA, the researchers trained rats to escape from a maze and then randomly divided the animals into three groups. After six weeks, the rats were put through the maze again. The animals that had been given only the fructose navigated the maze about half as fast as the rats that drank only water — indicating that the fructose diet had impaired their memory. The rats that had been given fructose and DHA, however, showed very similar results to those that only drank water — which strongly suggest that the DHA eliminated fructose’s harmful effects.

Other tests revealed that the rats receiving a high-fructose diet had much higher blood glucose, triglycerides and insulin levels than the other two groups. Those results are significant because in humans, elevated glucose, triglycerides and insulin are linked to obesity, diabetes and many other diseases.

The research team sequenced more than 20,000 genes in the rats’ brains and identified more than 700 genes in the hypothalamus and more than 200 genes in the hippocampus that were altered by the fructose. Of those 900 genes they identified, the researchers found that two in particular, called Bgn and Fmod, appear to be among the first genes in the brain that are affected by fructose. Once those genes are altered, they can set off a cascade effect that eventually alters hundreds of others, Dr. Yang says. That could mean that Bgn and Fmod would be potential targets for new drugs to treat diseases that are caused by altered genes in the brain.

The research also uncovered new details about the mechanism fructose uses to disrupt genes. The scientists found that fructose removes or adds a biochemical group to cytosine, one of the four nucleotides that make up DNA. This type of modification plays a critical role in turning genes “on” or “off.”

“Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders,” EBioMedicine, April 13, 2016


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