Daily hormone injections helped dieters keep weight off in a study that helped shed light on why it is so easy to gain weight and so hard to keep it off, researchers said on Thursday.
Their study showed that the hormone leptin, useless for helping people lose weight, could help people maintain weight loss — as long as they got twice-daily injections.
The finding helps researchers understand the complex way that human bodies regulate metabolism and put on fat, said Dr. Michael Rosenbaum of the Columbia University College of Physicians and Surgeons in New York.
"Anybody who has ever lost weight and tried to keep it off knows ... that you never lose as much weight as you think you should. And if you manage to lose as much weight as you'd like to, it's very, very difficult to keep it off," Rosenbaum said in a telephone interview.
In the 1990s, scientists discovered leptin, a hormone produced by fat cells that caused rats to lose weight when injected. But it failed to have the same results in humans, except for people with a defect in the leptin gene.
Other hormones associated with hunger, metabolism and weight, such as neuropeptide Y and ghrelin, have had similarly disappointing results — indicating that obesity is far more complicated in humans than in rodents.
The study of 10 obese and non-obese volunteers showed it is possible to restore leptin levels to a pre-weight-loss point, and in turn keep a dieter's weight stable.
"The importance of this is understanding how leptin works. This study was not designed specifically to look at weight reduction therapy," said Rosenbaum, whose team reported their findings in the Journal of Clinical Investigation.
"If you give leptin to someone at their usual body weight ... nothing or almost nothing happens," Rosenbaum said.
"If I give leptin to you when your weight is stable after you lose weight, it reverses many of these systems that have conspired against you previously, so they are kind of happy that you have lost weight."
But the effect is not permanent. It seems the body can reset its metabolic thermostat upward, to put on weight, but never downward, Rosenbaum said. This explains why 85 percent of people who lose weight eventually put it back on.
"People who sustain weight loss for extended periods of time are extremely metabolically efficient," Rosenbaum said. For years after a diet their bodies struggles to hang on to fat, expending less energy than before.
Weight loss drugs create an artificial state, he said, either unnaturally suppressing hunger or temporarily raising metabolism. The key to fighting obesity is to change metabolism naturally, he said.
The leptin signaling pathway may be a way to do this.
"Healthier diet and exercise have to remain at the heart of any weight loss therapy with or without pharmacologists involved," Rosenbaum said.
"But the idea is that instead of therapy designed to move us into an abnormal state of low appetite and high energy expenditure, there should be therapy designed to make our bodies imprint at a lower weight."
Their 10 volunteers all lost 10 percent of body weight on a very low calorie liquid diet of 800 calories a day for eight weeks, then received the leptin injections for 5 weeks.
"The primary functional role of leptin is apparently to defend — not reduce — body fat by increasing food seeking and decreasing energy expenditure when fat stores are insufficient," the researchers concluded.