The hormone leptin acts in the brain to regulate food intake and fat mass: low blood levels of leptin increase appetite and lower the body’s basal metabolism, whereas high leptin levels reduce appetite and promote fat breakdown. This effect of leptin has been known for 20 years, but exactly how the brain signals back to fat tissue to trigger fat breakdown has only now been unraveled, in a study funded, in part, by FCT.
In the latest issue of the leading journal Cell, the teams led by Ana Domingos, from the Instituto Gulbenkian de Ciência (IGC), and Jeffrey Friedman, from the Rockefeller University in New York, elegantly show that leptin acting in the brain stimulates nerve cells that envelop fat cells, activating a series of reactions in the cells that ultimately lead to breakdown of fat. Their results suggest that directly activating the nerve cells in fat tissue may be an alternative route to induce fat loss, in particular in cases where people may be resistant to leptin.
The first step was to determine whether fat tissue is innervated at all. Using highly sensitive imaging techniques, the researchers found that fat cells of mice are encapsulated by nerve cells belonging to the so-called sympathetic nervous system. The researchers went on to show that when the ends of these nerve cells are directly stimulated, a neurotransmitter called nor-adrenaline is released, which triggers a cascade of reactions in the fat cells, culminating in the breakdown of fat and subsequent loss of fat mass. Without these nerve cells, or without the pieces of the chemical cascade, either in the nerve cells or in the fat cells, leptin is unable act.
When the effect of leptin on food intake and fat breakdown was first discovered, scientists thought that it might become a powerful treatment for obesity. However, it was later found that, in many cases, the brain of obese people does not respond to the satiety message carried by the leptin produced in their fat tissue; the body continues to crave food and the fat in excess is not broken down. These latest results add an important new piece to the leptin puzzle, and open new avenues for treating resistance to leptin.
This work was funded by FCT, the European Molecular Biology Organisation (EMBO) and the JPB Foundation. The IGC is an FCT-funded R&D centre, graded as Exceptional in the latest evaluation carried out by FCT (2013/2014).
Image credits: Instituto Gulbenkian de Ciência (IGC).