July 27, 1995 in Nation/World

Hormone May Trigger Weight Loss ‘Leptin’ Called Advance In Research On Obesity

Los Angeles Times
 
Tags:health

Perhaps heralding a leaner future for an ever-fatter America, scientists have gotten genetically obese mice to lose a third of their weight in two weeks by injecting them with a newly discovered hormone that regulates body fat.

Besides studying the grotesquely obese mice, the scientists, led by Jeffrey M. Friedman, a molecular geneticist at Howard Hughes Medical Institute and Rockefeller University, also have found a nearly identical hormone in human beings.

Moreover, while the thrust of the work involved the mouse hormone, the researchers also found that obese mice injected with the human hormone similarly lost weight. This suggests that the hormone might someday be used as a high-tech reducing drug in people.

Claiming the pioneer’s right to name the discovery, Friedman proposes calling the hormone “leptin,” from the Greek for “thin.”

“The fact that human leptin reduces weight in the mice raises the possibility that giving leptin to people might have similar effects,” Friedman said.

“Extremely exciting,” said Dr. Carl Grunfeld, an endocrinologist at the University of California, San Francisco, and the Veterans Affairs Medical Center. “This is perhaps the major finding in the field of obesity in the last two decades.”

“A wonderful advance,” said Dr. Susan Yanovsky, executive secretary of the National Task Force on the Prevention and Treatment of Obesity. “But we’re a long way from knowing what’s going on in human beings with obesity, or the best way to treat it.”

In the recent studies, Friedman and co-workers showed that obese mice injected with leptin lost an average 30 percent of body weight after two weeks.

The federal government estimates that 58 million adults, or a third of the adult population, are obese, which is defined as weighing 20 percent or more above the ideal weight. That’s a substantial jump from a decade ago, when a quarter of American adults were obese, according to the National Institute of Diabetes, Digestive, and Kidney Diseases.

The search for this heretofore elusive substance began in the early 1970s, when Douglas Coleman, a senior researcher at the Jackson Laboratory in Bar Harbor, Maine, showed that special, lab-bred obese mice appeared to lack something that controls appetite and body fat in other mice.

Last December, after eight years of experiments, Friedman and co-workers announced that they had identified a mutant gene in the obese mice that, they believed, made the creatures pile on fat.

Once the researchers knew the chemical code inscribed in that gene’s DNA, they used standard recombinant DNA techniques to insert a normal version of the gene into bacteria in test tubes. The bacteria then manufactured the gene product - leptin.

ot only did the leptin-treated obese mice trim down, the researchers reported, but other measures of metabolism also changed. Body temperature rose, appetite fell, and the animals became more active.

The range of leptin’s metabolic effects indicates that it plays a central role in both monitoring and controlling body fat and energy balance, researchers said.

Friedman said, in mice anyway, leptin appears to be secreted almost exclusively by fat cells. And the more fat on board, the more leptin in the bloodstream.

When leptin reaches a certain level, scientists believe, it signals those brain centers that control hunger and appetite, such as the hypothalamus, which is sometimes described as the body’s thermostat. In people with a normal leptin-producing gene, the brain then responds to the signal by regulating the body’s fat stores and energy balance.

In those with a defective gene, however, that feedback process does not work properly.

The obese mice offer graphic evidence for leptin’s vital feedback role. “Ironically, here’s a massively obese animal that thinks it’s starving because the signal’s been interrupted,” Friedman said.

“If leptin plays a role in humans, it’s likely to be in the morbidly obese, and not all of them,” said Dr. C. Wayne Callaway, an endocrinologist specializing in obesity at George Washington University.

An important social implication of the obesity gene research, researchers say, is that it shows that obesity is not a weakness or a failure of willpower. In that sense, this high-tech lab work may help erase some of the stigma of being fat.


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