Mouse fat-burning neurons grow on leptin

Fat-burning neurons have powers that were previously unrecognized. Mouse studies show that they have an amazing ability to grow if they get the right signal.

There is no doubt that you can reduce fat by reducing or eating less Move more— After decades of research, the biology underlying this equation remains a mystery. It is these nerves embedded in adipose tissue that actually stimulate the breakdown of stored fat molecules.

The signal is the hormone leptin, which is released by the fat cells themselves. In the experiment with the mouse described in 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 animal performance burn Energy stored in fat.

“The structure of the nervous system can change significantly with the development of young animals, but we didn’t expect adults to see this level of neuroplasticity,” says Rockefeller University molecule. Geneticist Jeffrey M. Friedman says.

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.

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 processed them for more than two weeks, a bigger 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 certain 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, that is to say fat, might explain why this part of the response to leptin took longer.

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 there, 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 functioning,” says Friedman. “This is 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’s bodies produce high levels of leptin, show a reduced response to hormone injections, and their brains Resistant For hormones. Therefore, avoiding leptin resistance may have therapeutic benefits in these patients.

“A new study found that obese leptin-resistant animals, as well as animals lacking leptin, show diminished fat innervation,” Friedman said. “Thus, we speculate that directly activating the nerves that innervate fat and restoring the normal ability to use stored fat could provide a possible new avenue for treating obesity.”

Source: Rockefeller University