Appetite-Suppressing Hormone Discovered

WASHINGTON - Scientists have discovered a biological brake for a hunger hormone: a competing hormone that seems to counter the urge to eat. The substance, named obestatin, has been tested just in laboratory rats so far. But if it pans out, the discovery of the dueling hormones could lead not only to a new appetite suppressant, but also help unravel the complex ways that the body regulates weight. It turns out that the same gene sparks production of the two opposing hormones, Stanford University researchers say in Friday's edition of the journal Science. "It is an unexpected but very, very intriguing finding," said Matthias Tschop of the University of Cincinnati, who reviewed the work. "It seems counterintuitive that Mother Nature would press on the brake and gas pedal at the same time." Years of additional research lie ahead to see whether obestatin might work as an appetite suppressor. Other weight-related hormones announced to great fanfare, such as leptin, have yet to lead to obesity treatments, and scientists now know that dozens of hormones probably are involved in the balancing act of weight gain and loss. But with one-third of American adults obese and only a few prescription drugs providing modest weight-loss help, every new clue generates intense interest. "Obese patients shouldn't get their hopes up yet," Tschop said. Among the crucial questions to be answered is whether obestatin made the rats eat less not because it directly suppressed their appetite but because it made them feel ill. People should not read too much into the new hormone's name. It's not a "statin" like that well-known class of cholesterol-lowering drugs. Instead, the name combines the Latin words for devour and suppression. The latest discovery stems from the hunger hormone called ghrelin. Produced in the stomach, it boosts appetite. The theory is that ghrelin helped early humans survive famine by fattening them up during times when food was plentiful, a mechanism that can backfire in today's culture of plenty. Obestatin is a sister hormone to ghrelin and is produced in the gut, too, Stanford endocrinologist Aaron Hsueh and colleagues discovered. It might be better dubbed the anti-ghrelin. Hsueh's team was scouring databases of genes from humans and other organisms in a quest to discover types of hormones that could be turned into drugs fairly easily. They narrowed their hunt to stretches of genes conserved through millions of years of evolution in far-ranging species, a sign that those sequences may be of particular biological importance. The genetic sequence that leads to ghrelin had an extra protein hanging on the end — obestatin. It was present in humans and at least 10 other mammal species. "It was really extraordinary to think the hormone had been sitting there in plain sight," Science deputy editor Katrina Kelner said. Hsueh then created a synthetic version of the hormone and set out to see what it does. Surprisingly, normal-weight rats injected with obestatin cut their food intake in half, leading to a 20 percent drop in weight over eight days. That is not a big weight loss, but these were not fat rats; they would have gotten sick had they lost too much. So Hsueh's next step is to test whether obestatin suppresses appetite and leads to more weight loss in obese rats. Obestatin also slowed the emptying of rodents' stomachs and the movement of food through the intestines, important steps in countering ghrelin's hunger-inducing effects. The stomach does not work alone, but is part of a complex gut-brain network where hormones and other substances in the stomach and intestines signal the brain about fullness or hunger. Indeed, Hsueh found that obestatin is present in rats' stomach and brain tissue. Moreover, the researchers also discovered the receptor where obestatin binds to cells so it can regulate gastrointestinal functions. That means in addition to studying obestatin itself as a potential drug, researchers can hunt for other substances that might suppress appetite by triggering that receptor. The research was funded by Johnson & Johnson Pharmaceutical Research & Development LLC.