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!
The balancing act: An enzyme that links endocytosis to membrane recycling
07.12.2016 | National Centre for Biological Sciences
Transforming plant cells from generalists to specialists
07.12.2016 | Duke University
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
07.12.2016 | Health and Medicine
07.12.2016 | Life Sciences
07.12.2016 | Health and Medicine