Natural Hormone May Lead to New Weight-Loss Drugs
Researchers have identified a hormone naturally produced by the body that cut the amount of food volunteers consumed by up to 36%, a finding that could eventually lead to new types of natural weight-loss drugs.
The hormone “is what stops you from having a third helping,” said Dr. Stephen Bloom of Imperial College in London, who led the study. The hormone, called PYY3-36, was shown to reduce food intake in rats over a long period, the team reports in today’s issue of the journal Nature.
New ways of controlling weight gain are desperately needed. Some researchers estimate that as much as 60% of the American population is overweight, and the obesity epidemic is extending to childhood. About 13% of children and 16% of adolescents are estimated to be overweight, and the proportion is growing rapidly, fueled by fast food and lack of exercise. New studies have shown that obesity is the second leading cause of preventable deaths, after smoking.
Weight-loss drugs and programs are a $40-billion-per-year industry--and growing. There are about 15 drugs for treating obesity that are in human clinical trials or about to begin them, according to a recent study by the market research firm Marketdata Enterprises Inc. But many diet drugs produce only modest weight loss. The loss does not persist for long periods and most drugs have undesirable side effects, such as hyperactivity and extreme dry mouth.
“If we are to combat the global obesity epidemic, such breakthroughs [as this] are urgently needed,” wrote Dr. Michael W. Schwartz of the University of Washington in an editorial in the same journal.
Experts agree that it will be years before a useful drug can be produced from the new finding--if one can be at all. One stumbling block, for example, is that the hormone cannot be administered orally because acids in the stomach would destroy it.
But this discovery certainly represents one of the most promising leads in recent years.
Many hormones that reduce appetite have been identified, “but this one has important features that distinguish it from the others,” said Dr. David E. Cummings of the Veterans Affairs Puget Health Care System and the University of Washington.
Its effects lasted longer than those of other hormones and repeated injections produced long-lasting appetite suppression and weight loss in rats, he said.
“Others don’t do this,” he said. They change eating patterns but don’t produce long-term weight loss. Moreover, most of the other substances previously identified have not been tested in humans, he said.
Cummings himself made a splash earlier this year with the discovery of another hormone, called ghrelin, that increases appetite. PYY3-36, he said, “is the anti-ghrelin.”
The existence of PYY3-36 has been known about for some time, but the new study is the first to show what it does.
Bloom and colleagues from Oregon and Australia demonstrated that the hormone, a peptide containing 34 amino acids strung together, is produced in the intestines following a meal. Its natural function is to make you stop eating because you feel full, said team member Dr. Caroline J. Small of Imperial University.
The team gave injections of the drug under the skin to rats that were exposed continuously to food, as well as to rats that had been starved for 24 hours. Both groups showed marked decreases in appetite. Importantly, the drug did not lose its effectiveness after repeated administration, as has been observed with many other such hormones.
The results were also significant, Cummings said, because the team administered the drug at very low doses that were comparable to levels found naturally in the bloodstream.
The British team then infused low levels of the hormone directly into the bloodstream of 12 human volunteers, while infusing a placebo into a control group of 12 other adults. Two hours later, all the volunteers were allowed access to a buffet. Those who received the hormone ate 36% less food than those who received the placebo. They continued to eat less for at least 12 hours.
Because PYY3-36 must be given by infusion, it is unlikely to become a significant weight-loss drug itself, Bloom conceded.
“But it may be possible to identify foods which cause the release of more PYY3-36, helping to naturally limit appetite, or it may be possible to create a tablet with a similar effect, providing an excellent, natural and safe long-term treatment for obesity,” Bloom said.
Researchers have many hurdles to overcome before then, noted Dr. Richard Atkinson, president of the American Obesity Assn. Rats exposed to many other appetite-limiting hormones have been shown to develop a tolerance, and some fear that humans would develop a similar tolerance to PYY3-36.
“They need to give this every day for months and see if it results in significant weight loss,” he said.
