U.S. scientists have identified a chemical in rats that naturally inhibits food consumption and helps control weight gain. The finding could offer insights for researchers developing obesity treatments, but they first must sort out the various functions of the growing list of hormones related to the body's energy balance.
In the past decade or more, scientists have discovered a bewildering array of hormones that help regulate body weight. This is a very active field of research, driven partly by increasing rates of obesity worldwide. Among the investigators is Matthias Tschop of the University of Cincinnati's Obesity Research Center.
"We are probably looking at even hundreds of factors that we know today are involved in the regulation of energy balance, food intake, body weight, body composition, and we don't know much yet about which ones are the essential ones and how all of these interact," he said.
Now, Stanford University School of Medicine scientists have introduced yet another factor into the mix. Taiwanese-born biologist Aaron Hsueh and colleagues have discovered a hormone called obestatin that, when injected into rats, dramatically decreased their food intake.
"The food intake is more than 50 percent down. The body weight is more like 20 percent down over an eight-day period," he noted. "This is a normal animal, and you don't expect a normal animal to go to half of its weight. That's a sick animal."
A statement from the journal Science, where Mr. Hsueh's study appears, says researchers thought they had found the last of the major weight regulating factors six years ago with the discovery of the hormone ghrelin, which increases appetite in rats.
The latest finding proves that notion wrong. Furthermore, it is unusual because it shows that obestatin is chemically related to ghrelin, a sister hormone produced by the same gene. It is biologically rare for one gene to produce two different proteins, especially hormones that have the opposite impact.
Matthias Tschop of the University of Cincinnati says their common lineage might help clear up some confusion caused by previous animal experiments on ghrelin. Scientists were perplexed about why animals lacking the gene failed to lose weight, since without it they also lacked ghrelin's appetite boost.
"Since we now know that obestatin has been removed at the same time as ghrelin has been removed -- so we have removed at the same time a hunger hormone and a satiety hormone. It becomes much more plausible that maybe the resulting mouse that's lacking that gene doesn't show much either of an increase or decrease in food intake," he explained.
Mr. Tschop says it seems counterintuitive to have a gene that is responsible for accelerating and slowing appetite at the same time, but he suggests that the obestatin and ghrelin hormones might act independently of each other in different cells or at different times in the hunger cycle.
The Stanford University scientists who discovered obestatin say it might have potential as an appetite suppressing drug for people who need to lose large amounts of weight for health reasons. The research was sponsored by the U.S. pharmaceutical company Johnson and Johnson, which has rights to the discovery and hopes to pursue it.
Mr. Tschop is cautious about the prospect for such a drug. He notes that the hormone's effect on weight loss in rats was much less than its impact on reducing food consumption.
"We don't know everything yet about how important that balance between obestatin and ghrelin is and if maybe there is even other players that we don't know that are involved, but this is certainly a major discovery," he said. "Although particularly obese patients shouldn't get their hopes up yet that there might be another drug, this is a step in the right direction."
The next step in Mr. Hsueh's research is to genetically engineer rats lacking the receptor to which obestatin binds, to see if the animals become obese without the appetite restraint. If they do, he will inject them with obestatin to see if it corrects the condition. The result will reveal whether this approach works and has promise for overweight people, who share the hormone.
