Fat - Geneticists report theyâ€™ve identified hundreds
of genes that appear to make worms either fat or slim. And this
may lead to big new anti-fat drugs. (1/15/03)
the Difference - Studies indicate that overweight people may
get more pleasure from eating. (12/10/02)
Obesity - Researchers have shown that a virus which causes
obesity in animals is also contagious. (7/5/01)
Elsewhere on the web
Cases of Obesity Caused by a Single Gene - Reuters
Overview of Obesity
Itâ€™s not just one gene, but many genes that can cause obesity.
As this ScienCentral News video reports, genetics researchers are studying
obesity, and the results may help drug designers create more effective treatments.
Divide and Conquer
Some diseases are caused by one gene. But more common are "complex"
diseases—like cancer, heart disease, diabetes, and obesity—that
are caused by many genes or sets of genes. Now geneticists have demonstrated
that they can subdivide obesity into different genetic causes. The study was
published in the journal Nature.
Researchers at Rosetta
Inpharmatics, a subsidiary of the pharmaceutical company Merck
collaborated with university scientists to combine clinical and gene sequence
information with new gene
chip experiments to find different groups of genes that underly obesity.
"What we want to be able to do is subtype individuals who have a particular
disease," says Eric Schadt, Director of Research Genetics at Rosetta,
"because these different subtypes may require different treatments to
Rosetta collaborated with UCLA geneticists Jake
Lusis and Thomas
Drake. They bred mice so that the geneticists knew details about their
genetic inheritance. They fed the mice a high-fat diet, "a Western diet
that was meant to simulate the type of diet that a lot of people [in] the
United States and Europe are eating these days—high in fat, high in
cholesterol," explains Schadt. They examined them clinically over time
for obesity traits such as weight, length and amount of fat.
Then they tested tissue samples from both mice that stayed lean and those
that got obese using high-tech “gene chips,” or microarrays. Gene
chips gather information about gene activity or “gene expression”—in
other words, which genes are turned on or off.
By studying the patterns of gene expression in the mice, Schadt and his team
were able to see differences in the genes of the obese and lean mice, and
identify genes that were associated with either obesity or leanness. Then
they found they could also separate the obese mice into two groups based on
their distinct patterns of gene expression.
Schadt explains, “They looked the same, clinically they were obese, but
their gene expression patterns said something differently, and that was that
they were being controlled by different genes. Their obesity was a result
of different causes.”
It might be revealed that some people are obese because their genes are affecting
the rate at which they metabolize food, and others because their genes are
affecting their perception of hunger, explains Schadt.
Treating the Cause
These discoveries are leading to a different way to treat many diseases, which
some call “personalized medicine.”
“Up until now, diseases such as depression and obesity have been assumed
to be similar for everyone,” says Stephen
Friend, president of Rosetta and a senior vice president at Merck. “Once
we know that it is a particular type of obesity that a patient has, it becomes
possible to identify the target that allows one to make a drug against that
component of that disease.
"More importantly," says Friend, "the chance that you could
discover a drug that would work in an individual, work in an actual patient,
and have a higher probability of working, is much higher once youâ€™ve
broken down a broad disease into the real diseases that were inappropriately
clustered as one before.”
Zeroing in on the genes that cause obesity will enable patients to be treated
based on the cause of their disease, not the symptom. Clinical trials can
be done more quickly and safely, because every person in a trial wonâ€™t
be given the same treatment. Patients can be assigned to treatment groups
and given drugs that are likely to be effective for them and wonâ€™t cause
Further studies into the possible roles these obesity genes play in the formation
of fat are underway at UCLA. According
to the American Obesity Association, approximately 60 million adults in
the U.S. are obese, and 9 million are severely obese.