Researchers have discovered how the protein Hap1, which is abundant in the brain’s hypothalamus, serves as the link between circulating insulin in the blood and the neural circuitry that controls feeding behavior in mice. Illumination of the neural pathway used by hormones to regulate appetite and eating behavior could eventually provide new drug targets for treating eating disorders and obesity. The research, reported on-line April 9 in the journal Nature Medicine, will be published in the May 1 print edition.
The hypothalamus serves as the central switching control for neural signals that regulate food intake and energy balance. Hormones such as insulin and leptin, which circulate in the blood plasma, are known to play an important role in regulating the brain’s feeding signals, but scientists have not fully understand how these hormones interact with the brain circuitry. Neurotransmitters in the hypothalamus, including GABA (gamma aminobutyric acid), are known to be an important part of the pathway that regulates feeding behavior.
Scientists at Emory University School of Medicine had previously identified the Hap1 protein as crucial for the normal function of the hypothalamus. In experiments with knockout mice in which the Hap1 gene was eliminated, the mice failed to eat after birth. In addition, deleting Hap1 caused degeneration of some neurons in the hypothalamus.
In order to find out more about the function of Hap1 and the neural pathways it employs, a team of scientists from Emory, The Rockefeller University, the Burnham Institute for Medical Research, and the University of California, San Diego, conducted a series of experiments in mice. They found that fasting increased the level of Hap1 in the hypothalamus of the mice and that administering insulin decreased the Hap1 level. Suppressing Hap1 expression through RNA interference reduced mouse food intake and body weight. They also found that reducing Hap1 decreased the level and activity of GABA receptors in the hypothalamus.
"We concluded that increased levels of Hap1 correlated with increased feeding behavior in the mice, and our research helps explain how Hap1 is linked to feeding-related molecules such as insulin, and to hypothalamic neuronal function," said Xiao-Jiang Li, PhD, professor of human genetics at Emory University School of Medicine and senior author of the study. "GABA is known to have a stimulating effect on feeding behavior. Because insulin decreases Hap1 levels, and reducing Hap1 decreases the GABA receptor activity, we believe Hap1 is the link between circulating insulin and the regulation of GABA receptors in the hypothalamus in controlling eating behavior."
"Scientists know that diabetes and obesity are related to abnormalities of hypothalamic function," Li said. "This is a complicated pathway, and Hap1 can help us explain it and hopefully manipulate it to treat disorders associated with abnormal energy balance in the brain."
Stuart A. Lipton, MD, PhD, director and professor of the Center for Neuroscience and Aging at the Burnham Institute for Medical Research in La Jolla, further stated, Òthe new work opens up additional targets for obesity research. For example, a drug that decreases Hap1 in the hypothalamus would decrease the electrical drive that underlies eating behavior, resulting in weight loss and potentially longer lifespan.
Holly Korschun | 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