“Leptin resistance is a significant factor, yet the mechanisms that underlie the problem remain unclear,” said Dr. Joel Elmquist, professor of internal medicine and pharmacology at UT Southwestern and senior author of the study appearing in the March issue of Cell Metabolism. “The fact that this cellular pathway may be involved is a novel observation.”
Leptin is a hormone released by fat cells that is known to indicate fullness, or satiety, in the brain. If the body is exposed to too much leptin, however, it will become resistant to the hormone. Once that occurs, the body can’t “hear” the hormonal messages telling the body to stop eating and burn fat. Instead, a person remains hungry, craves sweets and stores more fat instead of burning it.
Leptin resistance also causes an increase in visceral, or belly, fat, which has been shown to predispose people to an increased risk of heart disease, diabetes and metabolic syndrome.
For the current study, the researchers induced leptin resistance in organotypic brain slices from mice. This research technique, used commonly in neuroscience, enabled the researchers to maintain the cellular and anatomical relationships and some of the network connections that normally exist within the brain.
“We’re not dispersing cells. We’re leaving them in a microenvironment that simulates what’s going on in the brain,” Dr. Elmquist said.
When the researchers began manipulating the network – known as cAMP-EPAC pathway – they found that activating this previously unexplored signaling avenue is enough to induce leptin resistance within hypothalamic neurons, a critical site of leptin action. They also found that when the pathway was blocked, the cells were no longer resistant to leptin.
“In the follow-up experiments, which we conducted in mice, we were able to induce leptin resistance simply by infusing activators of this pathway, further supporting our theory that this signaling pathway may contribute to leptin resistance in obesity,” said Dr. Makoto Fukuda, instructor of internal medicine at UT Southwestern and the study’s lead author.
Dr. Elmquist said that while the EPAC signaling pathway itself is not novel, this is the first time it has been studied in the hypothalamus and in the context of energy balance and leptin signaling.
The next step, Dr. Elmquist said, is to investigate how critical the EPAC pathway actually is in leptin responsive neurons and to determine its role in maintaining energy balance and leptin sensitivity.
“These results are potentially interesting and provocative, but the physiological importance remains to be seen,” Dr. Elmquist said. “If, however, this pathway is indeed important, it will offer new insights into the mechanisms that high levels of leptin cause in leptin resistance.”
Other UT Southwestern researchers involved in the study were Drs. Kevin Williams and Laurent Gautron, both instructors of internal medicine.
The study was supported by the National Institutes of Health, American Diabetes Association, American Heart Association and the Smith Family Foundation.This news release is available on our World Wide Web home page at
Kristen Holland Shear | Newswise Science News
‘Farming’ bacteria to boost growth in the oceans
24.10.2016 | Max-Planck-Institut für marine Mikrobiologie
Calcium Induces Chronic Lung Infections
24.10.2016 | Universität Basel
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
24.10.2016 | Earth Sciences
24.10.2016 | Life Sciences
24.10.2016 | Physics and Astronomy