Discovery of how the brain controls fat breakdown

The hormone leptin acts on the brain, regulating food intake and fat mass: low leptin levels increase appetite and decrease basal metabolism, while high leptin levels 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 FCT, has it been discovered how the brain signals back to adipose tissue and triggers fat breakdown.

In the latest edition of the prestigious journal Cell, teams led by Ana Domingos, from the Gulbenkian Institute of Science (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 fat degradation. These results suggest that direct activation of nerve cells in adipose tissue may be an alternative way 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 sympathetic nervous system. The teams then showed that when the endings of these nerve cells are directly stimulated, they release a neurotransmitter called noradrenaline, which triggers a cascade of reactions in fat cells, culminating in fat breakdown and subsequent fat loss. In the absence of these nerve cells, or the molecules in the chemical cascade, either in nerve cells or fat cells, leptin cannot act.  

When the effect of leptin on food intake was discovered, everything pointed to the discovery of a new treatment for obesity. However, it later became apparent 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 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 an Exceptional rating in the latest evaluation (2013/2014). 

Image credits: Gulbenkian Institute of Science (IGC)