MORE NEWS ON LEPTIN
By Sean Henahan, Access Excellence
New research provides an improved understanding of the
role of leptin, a protein produced by the "obese" gene, in weight
gain in humans, report investigators at Rockefeller University.
Earlier this year a team led by Jeffrey Friedman, M.D., Ph.D., professor
at The Rockefeller University gained much public attention with a
study documenting a 30 percent weight loss in genetically obese
mice given daily injections of leptin for two weeks. While
receiving leptin, the mice ate less and increased their use of
In their latest study, the same investigators found that the
greater the body mass and percent of fat, the higher the levels
of leptin. In humans, the amount of leptin in blood highly
correlated to a person's percent of body fat and his or her body
mass index. However, the leptin level varied greatly from person
to person. For example, the amount of leptin for some obese
patients with BMIs larger than 40 was the same as for patients
with BMIs less than 20.
"We found the amount of leptin highly correlates to how much fat
is stored in the body, with greater levels found in individuals
with more fat and reduced levels in those who dieted. However,
not all obese patients have increased levels, which suggests
there may be important differences in the cause of obesity," said
Among the 87 lean and obese people in the study, 59 were
Americans of different ethnicities and 28 were Pima Indians, a
population with high rates of obesity. The people ranged in age
from 20 to 65 and included 50 women and 37 men. For two days
prior to the study, all participants ate a standardized, 35
percent fat diet that was calorically adjusted to maintain their
weight. The Pima Indians received a diet that was 30 percent
Women had significantly more leptin than men. However, when
compared by percent of body fat, women and men had similar leptin
levels. "The greater absolute leptin levels in women reflects
that they have higher body fat content than men," Friedman
The 13 dieting participants ate low calorie diets, 520 to 800
calories per day. The investigators measured individual's leptin
levels in blood samples and ob gene activity in fat tissue.
Dieting decreased leptin levels in the 13 volunteers. In general,
the greater their initial leptin level, the more it declined with
dieting, noted Friedman.
In animal studies, the scientists found that leptin levels
related to BMI. Specifically, when the researchers compared
normal weight mice from the same litters to four kinds of
genetically overweight mice, the leptin levels were 10 times
greater in diabetic (db) and yellow agouti (Ay) mutant mice,
five-fold more in fat mutant mice and twice as high in tubby
(tub) mutant mice. Also, three strains of overweight, nonmutant
mice had increased leptin levels ranging from 25 to seven times
more than littermates. Leptin levels in fatty (fa) mutant rats
were 50 times greater than that of non-mutant litter mates.
In normal mice, leptin levels dropped to 60 percent of the
pre-diet amount after a three-day fast and 20 percent after a
six-day fast. In db mice, leptin levels did not drop after 15
days of restricted food, but after 28 days of dieting, the mice
had no detectable levels of leptin in their blood, and tests
revealed reduced ob gene activity.
Friedman and his colleagues think leptin acts as a signal of how
much fat is in the body to the brain's hypothalamus, which
coordinates basic body functions such as eating. Differences in
the fat's production rate of leptin, resistance to leptin at its
site of action or a combination of these factors could influence
eating behaviors and energy use to cause obesity or other
nutritional abnormalities, such as diabetes, the researchers
Reduced sensitivity to leptin in some patients could explain why
more leptin is found in obese people, the scientists note.
"Some obese people may make leptin at a greater rate to
compensate for a faulty signaling process or action," Friedman
says. "If resistance to leptin is partial, rather than complete,
more leptin may be required for action."
In addition, obesity may occur if genetic or environmental
factors affect body chemistry after leptin acts, notes lead
author Margherita Maffei, Ph.D., postdoctoral associate in
Leptin's signaling ability may also help explain the high rates
of regaining weight found among dieters, the investigators
report. "After dieting, the levels of leptin drop, suggesting
that less leptin is made and available to signal the brain,"
Friedman says. "This reduction may contribute to increased
hunger and slower metabolism. If this is true, leptin therapy
may help people maintain weight loss after dieting. However, we
first must continue with studies to determine the safety of
leptin as a possible therapy."
The instructions to make leptin are found in the obese (ob) gene.
Friedman and his colleagues cloned the ob gene in mice in 1994
and reported in July 1995 that it makes leptin, which is produced
only in fat cells and then is released into the blood stream.
The current findings were reported in the November 1995
the journal Nature Medicine.
Related information on the Internet
More On Fat