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 Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>