Study Identifies Uric Acid as New Culprit in Metabolic Syndrome

A team of researchers have found that uric acid plays a key role in causing metabolic syndrome.

Metabolic syndrome is a cluster of risk factors that increases the chances of high blood pressure, high levels of blood sugar, excess of body fat around the waist and abnormal levels of cholesterol. This group of risk factors elevates the risk of heart disease and other heart problems. The risk factors arise from insulin resistance accompanying abnormal adipose deposition and function.

Researchers at the Washington University, St. Louis, found that excess levels of uric acid - the normal waster product excreted from the body by the kidney and intestine that is released in the urine and stool - is the main cause for metabolic syndrome.

When levels of uric acid are high they are known to cause gout, an accumulation of the acid in the joints. High uric acid level is also known to be linked with markers of metabolic syndrome. But not much is known about whether uric acid itself is causing the damage or is a simple byproduct of other processes that cause dysfunctional metabolism.

The new study reveals that high levels of uric acid in the blood is no bystander, but plays a key role in disrupting normal metabolism

"Uric acid may play a direct, causative role in the development of metabolic syndrome," said first author Brian J. DeBosch, MD, PhD, an instructor in pediatrics. "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."

Senior author of the study Kelle H. Moley highlighted that GLUT9 is a protein that is a key transporter of uric acid.

In this study, researchers conducted experiments on mice to notice what happens when GLUT9 stops functioning in the gut, blocking the body's ability to remove uric acid from the intestine. They noticed that kidney's ability to remove uric acid remained normal.

Mice with no GLUT9 in the gut developed high levels of uric acid in the blood and urine as compared to the control mice. At 6-8 weeks of age they had signs of metabolic syndrome. Some of the metabolic health improved with intake of drug called allopurinol. This drug also helped lower blood pressure and total cholesterol levels.

Most of the diet contributes to uric acid level. Many foods contain compounds called purines that break into uric acid. Also, fructose metabolism in the liver triggers uric acid production.

"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 was documented in Nature Communications.