Team Wins $2.2 Million to Expand Study of Innovative Obesity Therapy

By Eric Sauter and Mika Ono

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have been awarded nearly $2.2 million by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH) to advance an innovative approach to the treatment of obesity, a serious health problem that affects more than one-third of all Americans.

Anutosh Chakraborty, a TSRI assistant professor, is the principal investigator of the new five-year project.

Obesity, especially when combined with type 2 diabetes, leads to conditions including coronary heart disease, stroke, hypercholesterolemia, fatty liver, sleep apnea, osteoarthritis, certain cancers and various other diseases. If current trends continue, the number of Americans who are obese could reach 50 percent by 2030, according to the Trust for America's Health and the Robert Wood Johnson Foundation. According to Britain’s Fiscal Times, the estimated cost of obesity in the United States is already $305.1 billion annually. Current medications have limited success.

In an effort to address this dilemma, scientists want to identify relevant proteins, especially enzymes, to target with new and more effective drug candidates.

“Anti-obesity drugs generally work on reducing how much you eat or absorb,” Chakraborty said. “We investigate the problem from a different perspective.”

Chakraborty and his colleagues discovered that an enzyme called inositol hexakisphosphate kinase-1 (IP6K1) plays a significant role in promoting the action of insulin on energy/fat storage. Mice without IP6K1 are not only lean on regular chow diet, they are also protected against high-fat-diet-induced obesity and insulin resistance.

“IP6K1 knockout mice eat a similar amount of food, yet are lean as they efficiently expend the extra energy,” he said. “For us, that means that IP6K1 is the regulating factor when it comes to energy storage. Conversely, abnormal regulation of IP6K1 leads to obesity and insulin resistance. The new grant will allow us to identify the underlying mechanisms of how it works.”

In addition to gaining a broader understanding of the fundamental mechanism by which IP6K1 regulates metabolism, Chakraborty and his colleagues—including Scripps Florida’s Ted Kamenecka, assistant professor and associate scientific director of the Translational Research Institute, and Michael Cameron, associate professor of molecular therapeutics and DMPK—are working on the development of drugs which are expected to treat obesity, type 2 diabetes and other metabolic diseases via IP6K1 inhibition.

The number of the grant is 1R01DK103746.

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