Some headlines portended a miracle cure for fatness. “New hormonal supplement curbs appetite,” trumpeted one.
Hold off on the celebratory sundae.
It’s true that Medical Center researchers in Aaron Hsueh’s lab discovered a small peptide hormone that could lead to treatment for obesity—welcome news at a time when the Centers for Disease Control and Prevention estimates that 65 percent of Americans over the age of 20 are overweight or obese. But there’s no wonder pill on the immediate horizon.
For one thing, the appetite-suppressing hormone, dubbed obestatin, breaks down in the stomach. “Do people really want to inject themselves three times a day?” Hsueh asks. Even if a pill or nasal spray were developed, “obesity is not going to be solved by this, because there are psychological reasons for it, and many factors involved.”
Anyway, combating obesity isn’t really Hsueh’s objective. He’s a professor of obstetrics and gynecology. How did a reproductive endocrinologist make a pathbreaking obesity discovery? “Lots of people have asked me that,” he laughs. “With the advent of the genome project, it became obvious that we had to trace the evolutionary roots of hormones.” The boundaries between medical disciplines suddenly blur, Hsueh says, when researchers discover that fruit flies, which have no pituitary gland, nonetheless have a gene similar to the human gene that makes luteinizing hormone, which regulates the menstrual cycle.
Hsueh and his team used data from the genome project to identify gene sequences that had been preserved during hundreds of millions of years of evolution, suggesting biological significance. The sequence containing obestatin appears in 11 different species, including dogs, cats, bovines, porcines, monkeys and humans. “There’s a common ancestor for all of these mammals,” Hsueh says. If there are substantial changes in the gene sequence and the sequence affects something important, “this organism will not survive,” Hsueh says. “We looked at the region and said, ‘Wow—in all 11 species it does not change at all.’ ”
The sequence also contains ghrelin, an appetite-boosting hormone discovered in 1999. The fact that ghrelin and obestatin come from the same gene but have opposite effects was “a big surprise,” Hsueh says. He and his team synthesized the obestatin hormone and injected it into laboratory rats. Eight days later, the rats were eating only half as much as they had previously, which suppressed their weight gain. The research was sponsored by Johnson & Johnson and published in November in Science.
