TURNING BAD FAT IN TO GOOD, A FUTURE TREATMENT FOR OBESITY
By knocking down the
expression of a protein in rat brains known to stimulate eating, Johns Hopkins
researchers say they not only reduced the animals' calorie intake and weight,
but also transformed their fat into a type that burns off more energy. The
finding could lead to better obesity treatments for humans, the scientists
report.
"If we could
get the human body to turn 'bad fat' into 'good fat' that burns calories
instead of storing them, we could add a serious new tool to tackle the obesity
epidemic in the United States," says study leader Sheng Bi, M.D., an
associate professor of psychiatry and behavioral sciences at the Johns Hopkins
University School of Medicine.
More than two-thirds
of adults in the United States are overweight, and more than one-third are
obese, according to government estimates.
The Johns Hopkins
study, published in the journal Cell Metabolism, looks
at two types of fat made by the body: white and brown adipose tissue. White fat
is the typical fat that ends up around your middle and other places, and is the
storehouse for the extra calories we eat. White fat cells have a single large
droplet of lipid, one of fat's building blocks, such as cholesterol and
triglycerides.
Cells in brown fat,
considered a "good fat" for its energy-burning qualities, contain
many little droplets of lipid, each with its own power source, which enables
heat generation. Babies have ample stores of brown fat at birth as a defense
against the cold, but it mostly disappears, as adults have very little of this
calorie-burning tissue.
Bi and his
colleagues designed an experiment to see if suppressing the
appetite-stimulating neuropeptide Y (NPY) protein in the dorsomedial
hypothalamus of the brain would decrease body fat in rats. Located just above
the brain stem, the hypothalamus helps regulate thirst, hunger, body
temperature, water balance and blood pressure.
For five weeks, two
groups of rats were fed a regular diet, with one group also treated with a
virus to inhibit NPY expression and the other left as a control group. At the
end of five weeks, the treated group weighed less than the control group,
demonstrating that suppression of NPY reduced eating.
Then, researchers
split each of the groups into two, creating four sets of rats. One of the
treated groups of rats and one of the control groups were fed a regular diet
while the other treated and control groups got a high-fat diet. Of the rats on
the regular diet, the control group weighed more at the end of 11 weeks than
those rats in which hypothalamic NPY expression was knocked down. In the
high-fat group, the control group rats became obese; those rats in which NPY
expression was silenced gained less weight.
Bi says the results
"made sense," given that NPY has been shown to stimulate eating. The
less NPY, the less the rats would eat, his team hypothesized. What was a
surprise, however, was what they found after they checked the fat content of
rats after death. In the groin area of the NPY rats, researchers discovered not
the expected white fat found in adult rats, but the telltale signs of brown fat
in its place. They confirmed this change by looking at levels of mitochondrial
uncoupling protein-1, or UCP-1, through which brown fat burns to produce heat.
They used this protein as a marker to determine that the fat that should have
been white was instead brown.
Bi says he believes
that the transformation from white to brown fat resulting from NPY suppression
may be due to activation of brown fat stem cells contained in white fat tissue.
While brown fat seems to vanish in humans as they emerge from infancy, the
brown fat stem cells may never disappear and may just become inactive as people
age.
Bi says it may be
possible to transplant or inject brown fat stem cells under the skin to burn
white fat and stimulate weight loss. "Only future research will tell us if
that is possible," he says.
This study also
shows that low levels of hypothalamic NPY increase spontaneous physical
activity, improve blood sugar levels and enhance insulin sensitivity in rats,
but it remains undetermined whether this brown fat transformation also
contributes to these effects.
The study was funded
by the U.S. National Institute of Diabetes and Digestive and Kidney Diseases.
Along with Bi, other Johns Hopkins researchers involved in the study include
Pei-Ting Chao, Timothy H. Moran, Ph.D., and Susan Aja, Ph.D. Liang Yang, Ph.D.,
formerly of Johns Hopkins and now at the Massachusetts Institute of Technology,
also contributed.
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