Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Discover Master Metabolism Regulator with Links to Obesity, Heart Disease, and Malnutrition

07.02.2007
Two biologists at Penn State have discovered a master regulator that controls metabolic responses to a deficiency of essential amino acids in the diet.

They also discovered that this regulatory substance, an enzyme named GCN2 eIF2alpha kinase, has an unexpectedly profound impact on fat metabolism. "Some results of our experiments suggest interventions that might help treat obesity, prevent Type II diabetes and heart attacks, or ameliorate protein malnutrition," said Douglas Cavener, professor and head of the Department of Biology, who led the research along with Feifan Guo, a research assistant professor. Their research will appear in the 7 February 2007 issue of the scientific journal Cell Metabolism.

Organisms adapt metabolically to episodes of malnutrition and starvation by shutting down the synthesis of new proteins and fats and by using stores of these nutrients from muscle, fat, and the liver in order to continue vital functions. Cavener and Guo found that the removal of a single amino acid, leucine, from the diet is sufficient to provoke a starvation response that affects fat metabolism. "These findings are important for treating two major problems in the world," Cavener says. "The starvation response we discovered can repress fat synthesis and induce the body to consume virtually all of its stored fat within a few weeks of leucine deprivation. Because this response causes a striking loss of fatty tissue, we may be able to formulate a powerful new treatment for obesity."

The second problem is not excess food intake but insufficient protein intake, which plagues the populations of the poorer nations of Asia and Africa. The Food and Agriculture Organization of the United Nations estimates that 850 million people were malnourished between 1999 and 2005.[1] Those who eat a diet with sufficient calories that is lacking in an essential amino acid may suffer from stunted growth, developmental disorders, or even death. On the other hand, obesity is reaching near-epidemic proportions in wealthier nations. According to the Centers for Disease Control, 30 percent of U.S. adults over the age of 20 are obese.[2]

... more about:
»Cavener »GCN2 »Guo »HDL-cholesterol »Kinase »amino

Rather than working with cells in culture, Guo and Cavener examined metabolic processes in a special strain of mice that lacks the GCN2 kinase and compared them with those of normal mice. "Organisms are remarkably sensitive to dietary intake," Cavener says. "Being deprived of even one essential amino acid is enough for the GCN2 kinase to switch the metabolism into an emergency mode. Despite the fact that these mice are consuming normal amounts of carbohydrates and fats, they rapidly shut down fat synthesis in the liver and mobilize their stored fat deposits. Their bodies are literally tricked into a starvation mode."

The experiments conducted by Guo and Cavener had striking and unexpected results. After 17 days of a leucine-deficient diet, the normal mice lost 48 percent of their liver mass and 97 percent of the adipose or fatty tissue from their abdomens. This response is very similar to what happens during starvation. In contrast, the mice without the GCN2 kinase kept a steady liver mass and lost only 69 percent of the adipose tissue on their abdomens.

One of the especially encouraging aspects of the research by Guo and Cavener was the short time frame in which dramatic changes could be induced. Even after only 7 days of leucine deprivation, the normal mice lost 50 percent of their fatty tissue. They also produced fewer lipids (fats) and showed a small drop in serum triglyceride levels. The mice lacking the GCN2 kinase did not lose as much fat as the normal mice did and, in addition, they developed very pale, fatty livers with unusually high levels of stored triglycerides because they continued to synthesize fatty acids. The remarkable rapidity of the weight change in the normal mice occurred because the repressed synthesis of new fats was coupled with the depletion of stored fats in the body.

These findings about the crucial regulatory role of GCN2 kinase in the metabolism have major implications for the treatment or prevention of obesity, which is associated with increased risk for heart disease, diabetes, hypertension, and osteoarthritis. "Most of all," Cavener says, "we hope to be able to devise dietary interventions that will significantly improve the health of millions of children all over the world who suffer from amino acid deprivation associated with protein malnutrition."

The research was funded by the National Institutes of Health and the Pennsylvania Department of Health.

Barbara K. Kennedy | EurekAlert!
Further information:
http://www.psu.edu

Further reports about: Cavener GCN2 Guo HDL-cholesterol Kinase amino

More articles from Life Sciences:

nachricht Two Group A Streptococcus genes linked to 'flesh-eating' bacterial infections
25.09.2017 | University of Maryland

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

An international team of physicists a coherent amplification effect in laser excited dielectrics

25.09.2017 | Physics and Astronomy

LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

25.09.2017 | Trade Fair News

Highest-energy cosmic rays have extragalactic origin

25.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>