January

UMD Scientists Identify Genes that Turn On Nature's

Fat Burning Machine
Minnesotas ground squirrels
may hold the clues for a weight
loss aid.

Matt Andrews

Three UMD researchers, Professor

Matt Andrews in the Department
of Biology, Professor Marshall
Hampton in the Department of
Mathematics, and postdoctoral
researcher Dr. Richard Melvin,
have taken an unprecedented
approach to learning more about
brown adipose tissue, also know
as brown fat. They studied
Minnesotas thirteen-lined ground
squirrel and identified genes that
cause brown adipose to generate
heat by burning fat. This work is
significant because it paves the
way for pharmaceutical companies
to create drugs to enhance fat
burning in humans. Brown
adipose is natures fat burning
machine, said Andrews. We
know of no other organ or tissue,
other than brown adipose in a

January
hibernating mammal, that can
expend as much energy as fast.

Marshall Hampton

UMDs research, published on

December 30, 2013 in the
scientific journal PLoS
One, describes how the team
identified genes that are expressed
in brown fat by determining the
sequence of the initial products of
gene expression called messenger
RNA or mRNA. They used an
approach called transcriptomics to
identify and quantify the levels of
over 15,000 distinct brown
adipose mRNAs in active and
hibernating ground squirrels. In
the PLoS One paper they discuss
how the selective expression of
these genes can result in the
massive fat-burning activity of
brown adipose tissue.
Heres How it Works.

DIVERSE STUDIES NEEDED

Andrews stresses the importance of
biodiversity in research. He
advocates using different subjects
for experimental studies. The most
common experimental organisms in
research include rats, mice, fruit
flies, zebrafish, and baker's yeast,
but Andrews contends that this limits
new discoveries.
There is a whole world of plants and
animalsthat are full of biochemical
processes that can aid human
health, he said. The 13-lined
ground squirrel is an example of a
common Minnesota mammal that

Humans need fat. Our bodies use

white adipose (white fat) to store
excess calories for later use.
However, too much white fat can
result in weight gain. In 2007,
researchers discovered that adult
humans also have a tiny bit of
brown fat, which burns calories
incredibly fast. Babies are born
with brown fat because in the
past, they may have needed to
burn fat to stay warm and
survive.
The UMD research, led by
Andrews, studied brown fat in the
13-lined ground squirrel, a

January

holds a secret about fat burning that

cant be found in traditional research
organisms.
Andrews also has concerns about the
rapid extinction of species across the
planet. When we lose an insect in
the rain forest or a flowering plant in
North America, we have lost the
genetic and molecular information
about how these organisms survive
and adapt. Protecting biodiversity is
in our own self-interest because it
can unlock mysteries that benefit
humankind.

hibernating mammal. During

hibernation, ground squirrels lower
their body temperature and do not
eat. They use fat stored in white
adipose as their primary source of
fuel. When the squirrels awaken
from their deep sleep, their body
temperature rises from 42 to 98
degrees in less than three hours.
In this time, a large amount of fat
is burned in brown adipose,
creating heat like a furnace, to
raise the body temperature.

Andrews and Hampton studied the

expression of genes responsible
for this massive fat burning
activity. They determined that
over 2,000 brown fat genes change their expression during the hibernation season
including genes involved in hormonal signaling and fat breakdown. Their next step
was to use bioinformatics to determine if the ground squirrel genes correspond to
human genes, and almost all of them do.
From Gene Study to Drug Therapy.
The work Andrews and his team have done in this new research field has
implications for drug therapy. Harnessing this information from naturally
hibernating mammals will give researchers new pharmaceutical targets in the effort
to design drugs, said Andrews. Our work may help find a therapy that will sway a
white fat cell to use its own biochemical reactions to melt away fat.
The drug therapy technology isnt new. Over a decade ago, gene switching by RNA
interference was identified. In 2013, the U.S. Food and Drug Administration
announced its first approval of RNA interference strategy treatment. They approved
an injectable disease therapy, mipomersen or Kynamro, which is a drug that helps
lower a rare form of high cholesterol.
If our research with the ground squirrel can lead to a therapy that accelerates fat
burning, it has the potential to help people lose weight easier, Andrews said.