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mice missing protein burn more fat
By tina hesman Saey
Scientists are learning how they might
stoke the body’s fat-burning furnace by
turning up a molecular thermostat.
Mice lacking a protein that responds
to the hunger-promoting hormone
ghrelin burn more energy in their brown
fat than other mice, Yuxiang Sun of
Baylor College of Medicine in Houston
reported December 13. This
revved-up brown fat helps
keep mice lean and energetic
into middle age. The finding
could eventually lead to a way
to help people fight obesity.
Brown fat burns energy
instead of just storing it the
way white fat does. This
metabolically active fat is
important in helping rodents
and other animals maintain their body
temperature. Recently researchers
learned that adult humans have brown
fat, and that the amount of energy
burned by brown fat decreases with age
and weight. The discovery has spurred
interest in learning how to ramp up
brown fat activity.
Sun and her colleagues didn’t start
out trying to rev up brown fat. Because
the hormone ghrelin has been shown to
make animals eat more, the researchers
reasoned that blocking the molecule’s
activity might reduce appetite and help
animals and people lose weight. The
team genetically engineered mice to
completely lack either ghrelin or the
ghrelin receptor, a protein that interacts
with the hormone and sets off a series of
biological reactions in cells.
Disappointingly, mice lacking either
molecule ate and exercised just as much
as normal mice. But mice lacking the
ghrelin receptor burned more energy
and stayed lean even as they aged, while
normal mice and mice lacking ghrelin
tended to gain weight as they got older.
Mice missing ghrelin had a hard time
maintaining their body temperature in
the cold. But mice without the ghrelin
receptor stayed warm. Those pieces of
evidence led Sun and her colleagues to
examine brown fat in the mutant mice.
Sun’s team found that removing the
ghrelin receptor causes brown fat cells
to make more of a protein called UCP1.
That protein makes the cell’s
power plants less efficient
and as a result, they release
more heat. Inefficient brown
fat cells may burn their own
supply of fat and then gobble
up fat that otherwise would
be stored in white fat cells,
leading to leaner rodents,
Sun speculated.
If researchers can discover why removing the ghrelin receptor
turns up brown fat’s furnace, they may
be able to design a drug to do the same
thing. “There may be more than just
exercise and willpower that can keep us
in shape,” Sun said.
There is no question that increasing
the activity of brown fat can have a big
effect on weight, said Lewis Landsberg,
an endocrinologist at Northwestern
University in Evanston, Ill. Brown fat is
responsible for burning about 10 percent
of a rodent’s total calories. If brown fat
were to burn the same percentage in a
human who consumes 2,500 food cal-
ories per day, the fat would be burning
250 calories, about equal to the energy
burned by walking 2. 5 miles.
Landsberg said that it is not clear
whether removing the receptor directly
affects the energy expenditure of brown
fat or if the mutation somehow spurs the
nervous system to turn up the furnace.
Sun hopes to answer that question by
removing the ghrelin receptor just in
brown fat cells. s
“There may
be more
than just
exercise and
willpower
that can keep
us in shape.”
yuxiAng Sun
new cellular ‘bones’ revealed
Cells harbor several newly found
types of filaments, James Wilhelm
of the University of California,
San Diego reported December 12.
These filaments, formed from
strings of metabolic proteins, could
give researchers clues about how
the cell’s internal skeleton evolved.
In experiments with yeast, Wilhelm
and colleagues discovered that an
enzyme called CTP synthase can
make filaments. Wilhelm said the
researchers don’t yet know if the
filaments, found in human, fruit fly
and yeast cells, help form the cel-
lular skeleton. But another group
showed that the filaments do affect
the shape of some bacterial cells.
— Tina Hesman Saey
cells trained to make insulin
Sperm-forming stem cells in the
testes can be converted to insulin-
producing cells that could replace
diseased ones in the pancreas,
researchers from Georgetown Uni-
versity Medical Center in Washing-
ton, D.C., reported December 12.
Ian Gallicano and his colleagues
treated sperm-producing stem
cells from the testes of organ
donors with chemicals to coax the
cells into mimicking beta-islet
cells from the pancreas —the kind
that are compromised in diabetes.
The reprogrammed cells produced
insulin and curbed diabetes in
mice for about a week, and then
insulin levels dropped again. But
the cells would need to make much
more insulin to cure diabetes in
humans, and testes-derived stem
cells would be useful only for men.
Other stem cells might one day
help women with diabetes too.
— Tina Hesman Saey
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January 15, 2011 | science news | 9
