October 16, 2001
MEDIA CONTACT: Joanna Downer
Growing fat cells and nerve cells in the same dish has produced what is believed
to be the first demonstration of two-way communication between the cell types,
say Johns Hopkins scientists.
The achievement, using rat and mouse cells, provides the first clear evidence
that signals from fat cells can directly influence neurons outside of the brain,
the researchers say, with implications for understanding the storage and burning
of fat, obesity and related disorders, such as diabetes.
"It's been known for a long time that neurons outside of the brain communicate
to fat cells, but no one has thought much about whether fat cells can signal
back to the neurons," says first author Christine Turtzo, an M.D.-Ph.D.
candidate at The Johns Hopkins University School of Medicine. "We now have
evidence that fat cells directly signal neurons and influence their behavior.
Unless you had both types of cells growing together, you would not know."
Previously, fat cells were only known to influence the brain by producing substances
that would be carried through the blood stream. The brain was known to control
the burning of fat and to respond to its signals by sending messages through
the spinal cord and out to nerves located in and around the fat deposits. The
study shows that fat and nerve cells can influence each other without direction
from the brain.
The research, reported in the Oct. 16 online version of the Proceedings of
the National Academy of Sciences, used nerve cells from rats, and grew them
with fat cells from mice. The fat cells are similar to those from deposits known
as "white adipose tissue," the body's primary energy-producing fat
The experiments showed that fat cells affect nerve cells' production of a messenger
called neuropeptide Y (NPY). Also, the fat cells produce an as-yet-unidentified
factor that influences the nerve cells, says the study's principal investigator,
Daniel Lane, Ph.D., professor of biological chemistry in the school's Institute
for Basic Biomedical Sciences. He expects that human neurons and fat cells would
Turtzo discovered that nerve cells grown alongside fat cells produced more than seven times the NPY produced by nerve cells grown, or "cultured," alone. She also showed that adding insulin reduced the NPY levels in the mixed cells, but didn't impact the nerve cells grown alone.
"Because insulin doesn't affect these nerve cells, but does affect fat
cells, we believe the insulin is acting on the fat cells, which in turn affect
the neurons," explains Turtzo.
The role NPY plays in nerve cells that are outside the brain is not well understood.
Now, based on the results of their laboratory studies, the researchers suggest
that nerve cells outside of the brain secrete NPY to keep fat deposits from
being burned for energy, and the fat cells seem able to help regulate the amount
"The effects of NPY outside the brain make sense with what we know about
it in the brain," says Lane, who oversaw Turtzo's research. "In the
brain, high levels of NPY cause animals to eat ravenously, and in the periphery
it seems to block the mobilization of fat. If you're eating, you don't need
to burn stored fat."
Many of obesity's ill effects appear to stem from the large fat deposits that
develop in the abdomen. Interestingly, more nerve cells run through the fat
deposits in the abdomen than through fat stored in other parts of the body,
"Cross-talk between the neurons and the fat cells in the abdomen may be
particularly important in controlling what these fat cells make and secrete,"
says Lane. "Many investigators believe that these secreted factors act
on liver function in a manner, as yet unknown, to promote the onset of Type
2 diabetes, for example. Our approach may well shed light on these issues."
Co-author on the study is Ruth Marx of the department of neuroscience. The
project was funded by the National Institutes of Health.