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''Obesity Hormone'' Gene Mutation Found in Some Obese

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Misty

Thursday, November 22, 2001 3:58 AM

''Obesity Hormone'' Gene Mutation Found in Some Obese

http://dailynews./h/nm/20011031/hl/obesity_10.html

 

''Obesity Hormone'' Gene Mutation Found in Some Obese

By Merritt McKinney

 

NEW YORK (Reuters Health) - UK researchers said on Wednesday that they have

discovered certain obese people do have a genetic mutation that leads to low

levels of the ''obesity hormone'' leptin. The finding suggests that boosting

leptin levels with injections of the hormone may lead to weight loss in at

least some people, the researchers say.

 

But in an interview with Reuters Health, the study's lead author warned that

the research is preliminary.

 

The implications for people who are obese ``are only theoretical and

potential,'' according to Dr. Stephen O'Rahilly of Addenbrooke's Hospital in

Cambridge, UK. The findings suggest ``that there are some patients with

obesity whose leptin levels are somewhat lower than one would expect for

their fat mass,'' he said.

 

The discovery of leptin--a hormone released by fat cells and other tissues

that can tell the brain to curb appetite--was met with much fanfare and high

hopes that the drug could be used to treat obesity. However, most obese

people were found to have elevated levels of the hormone and thus can not be

helped by injections of the hormone.

 

In 1997, O'Rahilly and his colleagues reported the cases of two children who

lacked both copies of the leptin gene. Consequently, the children did not

produce any leptin. The children were ``ravenously hungry'' and became

severely obese very early in life, O'Rahilly said.

 

The children's cases suggested that leptin deficiency might be involved in

some cases of obesity and that treatment with the hormone might reduce

obesity. In fact, after one of the children started taking injections of

leptin, her appetite became normal and she began to lose weight.

 

But since then ``it has become clear that most obese people do not have an

absolute deficiency in leptin,'' according to O'Rahilly. In fact, leptin

levels tend to be higher in heavier people, he said.

 

``Giving extra leptin by injection to most people with obesity has not had a

dramatic effect on their obesity,'' according to the UK researcher.

 

The discouraging results of leptin injections as well as additional research

in rodents has led to the idea that a ''little bit'' of leptin is

sufficient, and ``after that other things determine your body fat mass,''

O'Rahilly said.

 

But a study of relatives of the original two children who lacked leptin

disputes this notion, O'Rahilly and his colleagues report in the November

1st issue of the journal Nature.

 

The researchers examined 13 people from three unrelated familes that had

children who lacked leptin completely. Unlike the children, who each had two

copies of a non-functional leptin gene, the relatives had only one mutated

copy of the gene. The other copy of the leptin gene was normal.

 

When O'Rahilly and his colleagues compared the relatives to a ``control''

group of people of the same ethnic background, they found that their leptin

levels were about half of what would have been expected. The relatives with

the single leptin mutation were also more likely to be obese than controls,

who had two working copies of the gene. And the relatives tended to have a

higher percentage of body fat than expected.

 

``These results suggest that moderate reductions in plasma leptin might

actually have an influence on fat mass, tending to push it up,'' O'Rahilly

said. The findings suggest that leptin levels are not only important ``at a

low threshold level,'' according to the researcher.

 

The results raise the possibility of using leptin injections to treat obese

people who have moderately low levels of the hormone, according to

O'Rahilly. Giving these people leptin injections might be beneficial, at

least theoretically, he said.

 

However, he cautioned that much more research is needed before prescribing

leptin to obese people.

 

``All we are saying is that our data suggest that such a trial may be

worthwhile,'' he said.SOURCE: Nature 2001;414:34-35.

 

 

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