Leptin rebuilds adipose tissue neurons and enhances calorie burning capacity

Ask 10 people to receive various answers about their weight loss keys. There are many hypotheses, from special diets to major exercises and the old adage “calories burned, calories burned.”

There is little doubt that you can lose fat by eating less or more. However, 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 experiments with mice, researchers found that a network of normally bushy nerve fibers in adipose tissue contracted in the absence of leptin and returned when the hormone was given as a drug. These changes have been shown to affect an animal’s ability to burn energy stored in fat.

Jeffrey Friedman, MD, a molecular geneticist at Rockefeller University, said:

If confirmed by humans, Nature In the paper, “Leptin-BDNF pathway regulates sympathetic innervation of adipose tissue” It may open up doors for advancing research on obesity and related diseases and developing new treatments targeting neurons in fat.

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. Mutations in the leptin gene (ob) cause severe obesity and metabolic disorders such as other adipose tissue functions regulated by the sympathetic nervous system. However, the basis of these sympathetic-related abnormalities remains unclear.

The findings reported here indicate that “ob/ob mice and leptin-resistant diet-induced obese mice show a significant reduction in sympathetic innervation of subcutaneous white and brown adipose tissue.”

Hormones relay signals between fat deposits 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, administration of leptin to mice rapidly reduces food intake and increases exercise. 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.

“The chronic leptin treatment of ob/ob mice restores adipose tissue sympathetic innervation, which is necessary to correct the associated functional defects,” the authors note.

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.

On the brain and back

Researchers use imaging technology developed in the laboratory by Dr. Paul Cohen, MD of Rockefeller, to visualize nerves inside fat and track the effects of leptin on fat-embedded neurons up to the hypothalamic region of the brain. Did. 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 added.

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,” Friedman said. “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 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. “A new study found that obese leptin-resistant animals, like 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.