"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 http://www.utsouthwestern.edu/home/news/index.html
To automatically receive news releases from UT Southwestern via e-mail, subscribe at www.utsouthwestern.edu/receivenews
Kristen Holland Shear | EurekAlert!
Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology
Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster
Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
23.11.2017 | Information Technology
23.11.2017 | Physics and Astronomy
23.11.2017 | Life Sciences