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Uric Acid Plays Key Role in Causing Metabolic Syndrome, Study

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Washington University researchers in St.Louis have found that uric acid is a key factor in causing metabolic syndrome.

Uric acid is a normal waste product removed from the body by the kidneys and intestines that is released in urine and stool. Higher levels of uric acid cause gout, an accumulation of the acid in the joints, and are associated with the markers of metabolic syndrome.

But until now, it hasn't been clear whether uric acid alone is the perpetrator or is it a byproduct of other processes that causes dysfunctional metabolism. The researchers said that excess uric acid in the blood appears to be one of the culprits in disrupting normal metabolism.

"Uric acid may play a direct, causative role in the development of metabolic syndrome," said first author Brian J. DeBosch, a professor in paediatrics, in a statement. "Our work showed that the gut is an important clearance mechanism for uric acid, opening the door to new potential therapies for preventing or treating type 2 diabetes and metabolic syndrome."

For the study, the researchers examined GLUT9 protein, a transporter of uric acid, in mice. They wanted to find out what happens when GLUT9 stops working in the gut and significantly blocks the body's ability to remove uric acid from the intestine.

The researchers found that the absence of GLUT9 caused elevated uric acid levels in the blood and urine in mice as compared to their counterparts in the controlled groups. Within 6-8 weeks of age, they developed hallmarks of metabolic syndrome: high blood pressure, elevated cholesterol, high blood insulin and fatty liver deposits, among other symptoms.

They also found that the drug allopurinol, which lowers uric acid production in the body and used in the treatment of gout, improved some of the measures of metabolic health. The drug lowered blood pressure and overall cholesterol levels.

"Switching so heavily to fructose in foods over the past 30 years has been devastating," Moley said. "There's a growing feeling that uric acid is a cause, not a consequence, of metabolic syndrome. And now we know fructose directly makes uric acid in the liver. With that in mind, we are doing further research to study what happens to these mice on a high-fructose diet."                       

The finding is published in the journal Nature Communications.

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