Skip to main content

Neuronal Connection Between Fat and the Brain Visualized

Researchers pinpoint the neurons within white fat tissue that mediate brain-bound leptin signaling and eventual fat breakdown.


The hormone leptin, produced by fat cells, acts as a satiety signal to the brain, resulting in fat breakdown when levels are high. The hormone, present in proportion to the amount of fat tissue, is known to act on hypothalamic neurons in the brain to tell an animal when it’s full and to kick-start the breakdown of fat. Now, a team led by researchers at the Instituto Gulbenkian de Ciencia (IGC) in Portugal and the Rockefeller University in New York City have, for the first time, provided direct visual evidence that some sympathetic neurons from the brain indeed terminate within fat cells. The researchers also used optogenetics to stimulate these neurons within a fat pad in mice and cause the breakdown of fat. Their results were published today (September 24) in Cell.
“This is a very comprehensive study with quite a beautiful dataset,” saidStephanie Fulton, who studies the neural pathways of food-motivated behavior at the University of Montreal in Canada and was not involved in the work. “[The authors] took advantage of powerful techniques to solidify the strong suggestion that white adipose tissue is directly innervated by the central nervous system and clearly demonstrate that leptin activates this sympathetic input.”
“It’s a real tour de force that combines really modern optogenetic and tissue clearing approaches that are being developed to understand the central nervous system [CNS] and are here applied to understand the neural action outside the CNS and in the body,” said Paul Kenny, director of the Experimental Therapeutics Institute at Mount Sinai Hospital in New York who was also not involved in the study.
Previous studies using neuronal tracing methods provided indirect evidence that neurons should be found within white fat tissue because they could not distinguish between neurons that were just passing through the tissue and those that had axon terminals within adipocytes themselves. Nor was there direct evidence for the function of these neurons in fat breakdown.
In the current work, Ana Domingos of the IGC and her colleagues first visualized the 3-D anatomy and structure of a dissected mouse fat pad using an ex vivo optical tomography technique. The fat organ was first made transparent by removal of the fat which leaves behind the extracellular matrix, vasculature, and neural structures. “Adipose tissue is an organ but the only image we have of it is as a blob,” said Domingos. “I wondered what the blob looks like from the inside, if there is there an anatomical complexity that may give us insight into the physiology of the organ.”
The team found axon bundles penetrating the organ. Then, using two-photon microscopy to image deep within the tissue, the researchers were able to visualize neural axons terminating within adipocytes in an intact fat pad in a living mouse. The sympathetic neurons in fat were sparse—the researchers estimated that less than 8 percent of the adipocytes had direct contact with the nerves.
The researchers then used optogenetics to stimulate the sympathetic neurons within a fat pad in mice. They found that these neurons released norepinephrine upon stimulation, as did leptin treatment. Both manipulations resulted in lipolysis—the breakdown of fat tissue. Conversely, genetically ablating the neural connections to the adipose tissue eliminated the effect of leptin. According toTamas Horvath, a professor of neurobiology at the Yale University School of Medicine who penned an accompanying perspective, this is the first study to apply optogenetic tools to probe the sympathetic nervous system.
While it was known that sympathetic neurons release norepinephrine and that adipocytes have receptors for norepinephrine, the source for the signaling molecule was controversial, as other sources of norepinephrine, such as the adrenal glands, are not required for weight loss, Domingos told The Scientist. “Finding these adipose junctions finally explains how adipose tissue receives its supply of norepineprhine in order to shrink the fat deposits,” said Domingos.
Next, Domingos would like to find pharmacological ways to specifically activate these adipose-associated neurons, mimicking the effect of leptin as a potential treatment for obesity.
For Kenny, the work is another example of the increasing appreciation for the brain-body connection. “This paper is revealing the broader body and brain connection that we are beginning to better appreciate,” he said.
“Lipolysis is another example of a basic process that occurs outside the brain that can be powerfully influenced by what occurs in the brain,” Kenny added. “The brain doesn’t function in isolation but communicates with other organs in beautiful ways.”

W. Zeng et al., “Sympathetic neuro-adipose connections mediate leptin-driven lipolysis,” Cell, doi:10.1016/j.cell.2015.08.055, 2015.

Source: http://www.the-scientist.com/

Popular posts from this blog

Gene therapy treats all muscles in the body in muscular dystrophy dogs

Human clinical trials are next step..
Source: www.healthcare.uiowa.edu
Muscular dystrophy, which affects approximately 250,000 people in the U.S., occurs when damaged muscle tissue is replaced with fibrous, fatty or bony tissue and loses function. For years, scientists have searched for a way to successfully treat the most common form of the disease, Duchenne Muscular Dystrophy (DMD), which primarily affects boys. Now, a team of University of Missouri researchers have successfully treated dogs with DMD and say that human clinical trials are being planned in the next few years.

"This is the most common muscle disease in boys, and there is currently no effective therapy," said Dongsheng Duan, the study leader and the Margaret Proctor Mulligan Professor in Medical Research at the MU School of Medicine. "This discovery took our research team more than 10 years, but we believe we are on the cusp of having a treatment for the disease."

Patients with Duchenne muscular dyst…

Schizophrenia symptoms linked to features of brain's anatomy?

Roger Harris/Photo Researchers, ISM/Phototake Using advanced brain imaging, researchers have matched certain behavioral symptoms of schizophrenia to features of the brain's anatomy. The findings, at Washington University School of Medicine in St. Louis, could be a step toward improving diagnosis and treatment of schizophrenia.
The study, available online in the journal NeuroImage, will appear in print Oct. 15.

"By looking at the brain's anatomy, we've shown there are distinct subgroups of patients with a schizophrenia diagnosis that correlates with symptoms," said senior investigator C. Robert Cloninger, MD, PhD, the Wallace Renard Professor of Psychiatry and a professor of genetics. "This gives us a new way of thinking about the disease. We know that not all patients with schizophrenia have the same issues, and this helps us understand why."

The researchers evaluated scans taken with magnetic resonance imaging (MRI) and a technique called diffusion ten…

The Nobel Prize in Chemistry 2015 for "mechanistic studies of DNA repair".

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry for 2015 to Tomas Lindahl Francis Crick Institute and Clare Hall Laboratory, Hertfordshire, UK
Paul Modrich Howard Hughes Medical Institute and Duke University School of Medicine, Durham, NC, USA &
Aziz Sancar University of North Carolina, Chapel Hill, NC, USA
“for Mechanistic Studies of DNA Repair"


The cells’ toolbox for DNA repair The Nobel Prize in Chemistry 2015 is awarded to Tomas Lindahl, Paul Modrich and Aziz Sancar for having mapped, at a molecular level, how cells repair damaged DNA and safeguard the genetic information. Their work has provided fundamental knowledge of how a living cell functions and is, for instance, used for the development of new cancer treatments.

Each day our DNA is damaged by UV radiation, free radicals and other carcinogenic substances, but even without such external attacks, a DNA molecule is inherently unstable. Thousands of spontaneous changes to a cell’s …