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From brain, to fat, to weight loss: New study reveals neural mechanism responsible for fat breakdown

Weight is controlled by the , which acts in the brain to regulate food intake and metabolism. However, it was largely unknown until now, how the brain signals back to the fat tissue to induce . Now, a breakthrough study led by at (IGC; Portugal), in collaboration with ’s group at Rockefeller University (USA), has shown that fat tissue is innervated and that direct stimulation of neurons in fat is sufficient to induce fat breakdown. These results, published in the latest issue of the prestigious journal Cell, set up the stage for developing novel anti-obesity therapies.

Fat tissue constitutes 20 to 25% of human body weight being an energy storage container, in the form of triglycerides. Twenty years ago Jeffrey Friedman and colleagues identified the hormone leptin, which is produced by fat cells in amounts that are proportional to the amount of fat, and informs the brain about how much fat is available in the body. Leptin functions as an “adipostat” neuro-endocrine signal that preserves body’s fat mass in a relatively narrow range of variation. Low leptin levels increase appetite and lower basal metabolism, whereas high leptin levels blunt appetite and promote fat breakdown. However, until now it was largely unknown what circuits close the neuroendocrine loop, such that leptin action in the brain signals back to the fat.

Microscopic image of fat cells encapsulated by nerve axons]
Microscopic image of fat cells (green) encapsulated by nerve axons (red) in mice
Image: Instituto Gulbenkian de Ciência