December 01, 1995
Signal Pathway Controls Creation of Fat Cells
According to
Ronald M. Evans
, body fat is not the inert,
butter-like substance you think it is. Instead, fat plays an active
role in the body, releasing and responding to hormones. What's
more, Evans's research suggests scientists may one day be able to
control fat development in the body.
In a paper published in the December 1, 1995, issue of
Cell,
Evans, an HHMI investigator and director of the Gene Expression
Laboratory at The Salk Institute for Biological Studies, and
colleagues reported the discovery of a previously unknown
hormone that determines the number of fat cells in the body. This
hormone serves as the "trigger" for signaling precursor cells
(fibroblasts) to differentiate into fat cells (adipocytes).
“Obesity is a complex problem with a real genetic aspect. Not many people are forceful enough to change their habits as required to fight it.”
Ronald M. Evans
Fibroblasts, Evans explained, have the potential to become fat,
muscle, or certain skin cells. The signals that cause fibroblasts to
follow one fate rather than another have long intrigued scientists.
Evans and colleagues introduced the newly discovered fat-
triggering hormonecalled 15d-PGJ2to fibroblasts in culture.
Then, using a technique developed by collaborator Bruce M.
Spiegelman at Harvard Medical School, they tracked the cells'
differentiation. Put simply, Evans said, "The fibroblasts became
adipocytes."
Because altered levels of 15d-PGJ2 play a role in the
development of obesity, a potential drug might block the
hormone's action, thus preventing fat cells from forming.
That's good news for the estimated 30 percent of
Americans who are obesethose whose body weights exceed
recommended levels by 20 percent. Obese individuals are
susceptible to a range of complications, including: non-insulin
dependent diabetes, hypertension, stroke, arthritis, gout, heart
disease, atherosclerosis, and certain types of cancer.
Evans explained that most of a body's fat cells are created
during embryogenesis and the first 10 years of life. So an
antagonist to block the action of 15d-PGJ2 won't melt fat from
adults. But therapies for those predisposed to obesityor for young
people who are becoming morbidly obesecould one day be based
on the signal pathway elucidated in the 15d-PGJ2PPAR
 interaction.
Genetically-based therapeutics may one day offer the best
solution to obesity-related health problems, Evans said. "(Obesity
is a) complex problem with a real genetic aspect. Not many people
are forceful enough to change their habits as required to fight it."
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