How the brain controls fat breakdown discovered

The hormone leptin acts on the brain, regulating food intake and the amount of fat mass: low levels of leptin increase appetite and decrease basal metabolism, while high levels of leptin reduce appetite and promote fat breakdown. This effect of leptin has been known for 20 years, but only now, in a study partially funded by the FCT, has it been discovered how the brain signals back to adipose tissue, and triggers the breakdown of fat.

In the latest edition of the prestigious journal Cell , teams led by Ana Domingos, from the Instituto Gulbenkian de Ciência (IGC) and Jeffrey Friedman, from Rockefeller University (New York), elegantly show that the action of leptin in the brain leads to the stimulation of nerve cells that encapsulate fat cells, activating a series of reactions in them, leading to the degradation of fat. These results suggest that direct activation of nerve cells in adipose tissue may be an alternative route to induce fat loss, particularly in people who have developed leptin resistance.

The first step was to determine whether adipose tissue is even innervated. Using highly sensitive imaging techniques, the researchers discovered that mouse fat cells are innervated by cells from the so-called sympathetic nervous system. The teams then showed that when the endings of these nerve cells are directly stimulated, they release a neurotransmitter called nor-adrenaline, which triggers a cascade of reactions in fat cells, culminating in the breakdown of fat and subsequent loss of fat mass. In the absence of these nerve cells, or of the molecules of the chemical cascade, whether in nerve or fat cells, leptin cannot act.  

When leptin's effect on food intake was discovered, it seemed like a new treatment for obesity had been discovered. However, it was later discovered that in many cases, the brains of obese people do not respond to the satiety message from leptin produced in their adipose tissue; the body continues to ask for food, and excess fat is not broken down. The results now obtained thus add an important piece to the leptin puzzle, and open new avenues in the search for treatments for leptin resistance.

This work was funded by FCT, the European Molecular Biology Organization (EMBO) and the JPB Foundation. The IGC is an R&D unit funded by the FCT, having obtained the Exceptional classification in the last evaluation (2013/2014). 

Image credits: : Gulbenkian Institute of Science (IGC)