SKINNY ON A FAT GENE
the difference between a fat mouse and a skinny mouse?
a lot when they're unwelcome visitors in your house. But to two
researchers at UMDNJ's Robert Wood Johnson Medical School (RWJMS),
that difference led to the discovery of a gene that might help unsuccessful
dieters and eventually may even eliminate obesity.
to Kiran Chada, PhD, a biochemist and director of the Genomics Center
at RWJMS, if a gene called HMGI-C is missing or only partially expressed
in mice, the animals do not gain weight even when fed a diet high
in fat. Chada and Ashim Anand, PhD, a postdoctoral research fellow
in biochemistry, made the discovery while studying a family of proteins-HMGI-C,
HMGI and HMGI (Y)- to understand the chemical signals that control
the growth of a developing mouse embryo.
results are significant because obesity is the second leading cause
of preventable death in the United States, but the development of
safe and effective drugs to fight it has so far proven elusive,"
said Chada. "And anyone who has tried to lose weight by dieting
knows permanent changes in behavior can be difficult." The study
was published in the March, 2000 issue of Nature Genetics.
HMGI-C genes in mice and humans are 98 percent identical. Based
on their research, the team realized all three genes, but specifically
HMGI-C, are essential to cell growth and differentiation during
embryo development. They designed a study to determine if HMGI-C
in mice might have any effect on fat accumulation. The researchers
discovered that the obese mice had HMGI-C in their fat tissues and
the lean mice did not. To prove that the HMGI-C gene was the controlling
factor in fat accumulation, they produced mice that lacked either
one or both copies of the gene.
study found that mice lacking the gene completely, or mice that
had only one copy, had an 87 percent decrease in the amount of fat
tissue as compared to normal mice fed a diet equal in fat content
to a high-fat American diet. The research revealed that mice lacking
the HMGI-C gene did not gain any weight, and that mice with one
copy of the gene also did not gain weight.
of the most exciting results of our study is that if expression
of the gene is inhibited by only 50 percent, weight gain does not
occur. This has important implications for drug development because
we have shown that the drug does not have to totally inhibit HMGI-C
to have a significant effect," Chada added.
New Jersey pharmaceutical companies have expressed interest in developing
a drug based on this research. A drug might be available in five
to 10 years following development and clinical trials, Chada said.
study was funded by the National Institutes of Health and the New
Jersey Commission on Science and Technology, which presented the
first $1 million research award to the Genomics Center.