Transcript here

The “Fat Gene”
Is it possible to cure obesity
with a pill?
Why study obesity? How does this
relate to healthcare?
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Nearly 1/3 of Americans are clinically
obese.
Almost 2/3 of Americans are considered to
be overweight.
These statistics have been on the rise for
over the past 100 years.
Obesity is a contributing factor in many
diseases including heart disease.
100’s of millions of dollars have been
poured into research by pharmaceutical
companies to try to develop a drug to
treat obesity.
How does this relate to
Biotechnology?
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In 1994 researchers at Rockefeller
University published a paper claiming to
have found the “fat” gene.
Since 1994 a multitude of papers on the
same gene have also been published.
Including a paper in 1995 by the same
group that mapped the human “fat” gene
to chromosome 7.
The ob gene
The gene they found is called the
ob (obese) gene. It was first discovered in
mice and later in humans.
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These mice contained a mutation
that over-expressed a specific gene.
The original study done on these
mice uncovered some interesting
information.
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The obese mice were sterile and prone to
sickness
Damage to the hypothalamus caused the
same phenotype.
Removal of fat from a mouse caused it to
eat more and restore the fat. This led to
the coining of the term lipostat.
If fat is removed from a normal mouse
and placed in another normal mouse,
that mouse will lose the fat.
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Joining a fat mouse to a normal
mouse causes the fat mouse to lose
weight.
Proteins from the fat of normal mice
can be injected into a fat mouse and
cause it to lose weight.
Diabetic mice share the same
phenotype as fat mice.
Leptin
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Researchers were able to determine
that the ob gene produces a protein
called leptin.
Leptin is believed to control the
lipostat of an individual.
How does leptin work?
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Leptin is secreted by fat cells.
An increase in leptin leads to a
decrease in hunger.
A decrease in leptin leads to
increased hunger and weight gain.
This works as a feedback loop to
control weight gain.
Is leptin the answer we have been
looking for?
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Is it possible to take a pill of leptin to
lose weight? NO!
Would leptin injections work?
Sometimes.
Gene therapy? Probably not.
We have to realize that only a small
percentage (<10%) of the obese
population has a mutation in the ob
gene.
Why were the ob mice sterile?
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In order to become reproductive a
person has to achieve a certain body
mass. Its believed that the level of
leptin in their bloodstream plays a
role in this.
How are ob mice related to diabetic
mice?
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It was determined several years ago
that diabetic mice lack the leptin
receptor.
Other functions of leptin
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Leptin receptors are present in:
• The pancrease
• Liver
• Kidneys
• Lungs
• Skeletal muscle
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This leads researchers to believe that
leptin plays a role in many processes
inside the body.
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Leptin plays a role in angiogenesis.
Leptin has been linked to
hypertension
Leptin has also been linked to sleep
apnea
What else is responsible for
controlling weight
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The brain plays a big role:
• There are over 15 different
neurotransmitters and enzymes found in
the brain besides leptin that regulate
appetite suppression and stimulation.
• This means that there are over 15
different pathways that regulate your
weight. That we know of.
What does this mean?
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Even though we have discovered the
genes that we believe are
responsible for obesity, we are not
very close to developing a drug to
fix/treat them.
The only way to lose weight
effectively is to exercise.