Lilly Discovers Breakthrough To Control The Hunger Hormone

Research points to a possible way to battle obesity. Lilly has discovered a hormone, made in the stomach, which tells the brain it's time to eat. 

In the battle to help Americans slim down, scientists have tried for years to unlock the mysteries of the "hunger hormone." The hormone, made in the stomach, tells the brain it's time to eat. Around the world, obesity researchers have wondered whether it was possible to manipulate the hormone, known as ghrelin, and help people tame their hunger.

Now, researchers at two institutions, including Eli Lilly and Co., say they independently have made a key discovery that one day could lead to a new medicine to reduce appetite and diminish obesity.

Both research teams say they have found an enzyme responsible for putting a fatty acid onto the hunger hormone. Without the fatty acid, the hormone might not have the same effect on appetite and the body's layering of fat. The enzyme is called GOAT, which stands for gastric O-acyl transferase.

"It's really the Holy Grail," said Jesus A. Gutierrez, a research adviser in integrative biology at Lilly. "It's something scientists have been looking for since 1999, when ghrelin was discovered."

Piling up unwanted pounds is a major epidemic in the United States. About two-thirds of U.S. adults are either overweight or obese, increasing their risks for coronary heart disease, stroke, Type 2 diabetes and other serious ailments, according to the Centers for Disease Control and Prevention.

Treatments for obesity-related diseases cost the health system billions of dollars a year in medicines, surgery and rehabilitation.

Discovering the enzyme is just the first step of a very long process in coming up with a new medicine to treat obesity. Lilly's chemists are now testing thousands of compounds, looking for a promising molecule that could block the enzyme. It's a painstaking, trial-and-error process that could take months or years to complete and then test in animals and humans.  Some outside scientists say the discovery could be key to figuring how to control hunger and weight gain.

But not all scientists agree that ghrelin is a key factor in obesity. Even the research papers call the role of ghrelin a controversial topic that could take much more study.

Researchers could take many approaches to trying to develop an enzyme inhibitor. One approach is to try to sop up the hormone with antibodies, which drug makers do for lots of diseases. Another approach is to try to block a receptor in the brain that gets the signal that the body is hungry.

Lilly's approach is to keep fatty acids from attaching to the ghrelin hormone while still in the stomach, before the signal is ever sent to the brain.

"In the realm of how hard it is to develop drugs, an enzyme in your stomach is a much easier target," said Dr. David Bredt, vice president for neuroscience research at Lilly. "This enzyme is only present in the stomach. It's not in the brain, where drugs can do harm. Secondly, when you take a pill, the first place it goes is to your stomach. So the pill doesn't have to go very far to work."

Source: Diabetes In Control: Lilly's research findings were published in the May issue of the journal Proceedings of the National Academy of Sciences. Another team, at the University of Texas Southwestern Medical Center in Dallas, published its discovery of the GOAT enzyme in the February issue of the journal Cell.