Studies show how leptin regulates the presence of neurons in fat

There is no doubt that you can lose fat by eating less or more. However, even after decades of research, the biology underlying this equation remains a mystery.

It is the nerves embedded in the adipose tissue that actually cause the degradation of conserved fat molecules, and new research reveals that these fat-burning neurons have previously unrecognized forces. became. They have an amazing ability to grow if they receive the right signal.

The signal is a hormone called leptin that is released by the fat cells themselves. In an experiment with mice described in the journal July 22 Nature, The researchers found that when hormones were given as drugs, the normally-busy network of nerve fibers in adipose tissue contracted and grew in the absence of leptin. These changes have been shown to affect an animal’s ability to burn energy stored in fat.

Although the structure of the nervous system can change significantly with the development of young animals, we did not expect adults to see this profound level of neuroplasticity. “

Jeffrey M. Friedman, Molecular Geneticist, Rockefeller University

If confirmed in humans, the findings could advance the study of obesity and related disorders and open the door for developing new therapies that target fat neurons.

Homing to fat neurons

The team began by exploring what happens to mice that do not produce leptin themselves and how they respond when treated with it.

Discovered in Friedman’s lab in 1994, this hormone relays signals between fat accumulation and the brain, allowing the nervous system to suppress appetite, increase energy expenditure, and regulate weight.

When mice are genetically engineered to stop producing leptin, they grow three times larger than normal mice. They eat more, have less movement, and the body’s inability to properly utilize fat to generate heat prevents it from surviving in an acceptable cold.

However, when these mice are given a dose of leptin, they immediately eat less and move more. But when researchers worked with them for more than two weeks, a deeper change occurred: animals began to break down white fat, which stores unused calories at normal levels, with another form of adipose tissue. Has regained the ability to use some brown fats, generating heat.

It was this slow change that the research team, including the first author of, was interested in. Nature Thesis, lab graduate student Putianqi Wang, and post-doctoral researcher Ken H. Loh.

They suspected that changes in neurons outside the brain (up to fat) might explain why this part of the response to leptin took so long.

On the brain and back

Imaging technology developed by Rockefeller’s Paul Cohen’s lab visualized nerves inside fat, and researchers tracked the effects of leptin on fat-embedded neurons up to the hypothalamic region of the brain. ..

From here, they found that the leptin growth-promoting message travels back through the spinal cord to fat neurons. “This study provides the first example of how leptin regulates the presence of neurons in both white and brown fat,” Cohen adds.

Through this pathway, fat seems to convey the amount of innervation needed for the brain to function properly. “Fat indirectly controls its innervation and is therefore functional,” says Friedman. “It’s an exquisite feedback loop.”

Future studies will analyze the role of this pathway in human obesity and perhaps provide new approaches for treatment. Most obese people produce high levels of leptin and show a reduced response to hormone injections, suggesting that their brain is resistant to hormones.

Therefore, avoiding leptin resistance may have therapeutic benefits in these patients. “In a new study, obese leptin-resistant animals, as well as animals lacking leptin, show diminished adipose innervation,” Friedman said. “Therefore, we speculate that directly activating the nerves that innervate fat and restoring the normal ability to use stored fat may provide a possible new avenue for treating obesity.