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The Way the Brain Controls Fat Breakdown Discovered

The hormone leptin acts in 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 degradation. This effect of leptin has been known for 20 years, but only now, in a partially FCT-funded study, has it been discovered how the brain signals back to the adipose tissue, and triggers fat degradation.

In the latest issue of the prestigious journal Cell, the teams led by Ana Domingos, from the Instituto Gulbenkian de Ciência (IGC) and Jeffrey Friedman, from Rockefeller University (New York), show, in an elegant way, 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 these cells, leading to fat degradation. These results suggest that direct activation of nerve cells in adipose tissue may be an alternative pathway to induce fat loss, particularly in people who have developed leptin resistance.

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

When the effect of leptin on food intake was discovered, it seemed that a new treatment for obesity had been found. However, it later turned out that in many cases, the brains of obese people do not respond to the satiety message from leptin produced in their fat tissue; the body continues to demand 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 Organisation (EMBO) and the JPB Foundation. The IGC is an R&D unit funded by FCT, having obtained the classification of Exceptional in the last evaluation (2013/2014).

Image credits: : Gulbenkian Institute of Science (IGC)