The Johns Hopkins Gazette: October 22, 2001
October 22, 2001
VOL. 31, NO. 8


Say What? Neurons and Fat Cells Have Dialogue in the Lab

Discovery could aid in the understanding of obesity and related disorders

By Joanna Downer

Johns Hopkins Gazette Online Edition

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 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 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 store.

The experiments showed that fat cells affect nerve cells' production of a messenger called neuropeptide Y, or NPY. Also, the fat cells produce an as-yet-unidentified factor that influences the nerve cells, says the study's principal investigator, Daniel Lane, professor of biological chemistry in the school's Institute for Basic Biomedical Sciences. He says he expects that human neurons and fat cells would behave similarly.

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," Turtzo explains.

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 the brain secrete NPY to keep fat deposits from being burned for energy, and the fat cells seem able to help regulate the amount of NPY. "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, Lane says.

"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," Lane says. "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.