A breakthrough study shows that fat tissue is innervated and that direct stimulation of neurons in fat is sufficient to induce fat breakdown. These results set up the stage for developing novel anti-obesity therapies. Fat tissue constitutes 20 – 25% of human body weight being an energy store in the form of triglycerides. 20 yrs 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 brain leptin action signals back to the fat.
Now, the research team led by Ana Domingos, combined a variety of techniques to functionally establish, for the first time, that white fat tissue is innervated. “We dissected these nerve fibers from mouse fat, and using molecular markers identified these as sympathetic neurons,” explains Ana Domingos. But most remarkable, “when we used an ultra sensitive imaging technique, on the intact white fat tissue of a living mouse, we observed that fat cells can be encapsulated by these sympathetic neural terminals.”
They used genetic engineered mice, whose sympathetic neurons could be activated by blue light, to assess the functional relevance of these fat projecting neurons. Through optogenetics, they locally activated these sympathetic neurons in fat pads of mice, and observed fat breakdown and fat mass reduction.” Ana Domingos adds: “The local activation of these neurons, leads to the release of norepinephrine, a neurotransmitter, that triggers a cascade of signals in fat cells leading to fat hydrolysis. Without these neurons, leptin is unable to drive fat-breakdown.” The conclusions and future directions are clear according to Ana Domingos: “This result provides new hopes for treating central leptin resistance, a condition in which the brains of obese people are insensitive to leptin.” Jeffrey Friedman adds: “These studies add an important new piece to the puzzle that enables leptin to induce fat loss.” http://www.eurekalert.org/pub_releases/2015-09/igdc-fbt092115.php
Highlights •The neuro-adipose junction in white adipose tissue is visualized in vivo •Adipocyte-projecting neurons can completely envelop an adipocyte •Leptin stimulates lipolysis via sympathetic neurons in fat •Optogenetic activation of sympathetic fibers in fat drives lipolysis and fat mass reduction
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