31 AUGUST 2006
Hungry? Then it's time to eat. But how do you know the time is right?
You have to rely on your brain to get its signals straight, to direct the proper actions in response to things like the levels of insulin and sugar in your blood.
Sure enough, the brain is usually pretty good at this. Several parts of the brain
play a part in feeding, and when a body is hungry, nerve cells in those regions
fire their electrical signals at a rapid rate. Researchers at Duke University
Medical Center found clear patterns of firing activity (in rat brains) across
cycles of being hungry, being full, and getting hungry again.
Their report, appearing in the August 17 issue of the journal Neuron, found hunger-sensitive nerve cells in the hypothalamus, part of the frontal cortex, and the amygdala and insula, brain structures involved in emotion. But the activity of individual cells alone did not correspond precisely with the rats' eating behavior. Rather, the overall activity of the whole population of nerve cells provided the most accurate guide to meal times. Individual nerve cells, it seems, report on various distinct aspects of the body's metabolic condition. The network of all the cells as a whole adds up the various inputs to determine when it's time for dinner.
That's not really a big surprise, because networks of cell activity are what makes complex life possible to begin with. Networks of cells make organs, and networks of organs make a body. The way those networks fit together to make a functioning biological machine is pretty fascinating.
Even more fascinating, though, is the more recent discovery of life's networking skills on the level of molecules.
Eating, after all, is all about providing your body with the molecules it needs to build its cells and provide them with energy. And bodies are built from the bottom up, as genes guide the production of specific biomolecules (using the raw material molecules from food). Genes are turned on at different times and places in the body so that the right molecules will be around where and when they are needed.
But how do genes know when to turn on and off? By the presence of molecules made by other genes. Those genes may be turned on by other gene products, or by molecules activated by substances entering the body from the outside (such as food), or stimulated in other ways (such as by light or other sensations). It means that life at the most basic levels is governed by complex networks of molecular interactions.
In fact, such networks may be even more complex than biologists have realized. A particularly important family of cellular molecules, it seems, participates in a "meganetwork" of activity responsible for some of life's most important processes.
Molecular biologist David Mangelsdorf and colleagues report in the August 25 issue of Cell on a group of proteins known as nuclear receptors, sensor molecules that respond to various hormones, vitamins and fats. When stimulated by the proper molecule, a nuclear receptor becomes a gene-activating factor, telling the cell's DNA to start producing a particular protein. Genes controlled by these nuclear receptors make molecules important for many of the major processes of life, including metabolism, reproduction and the working of the immune system. Consequently nuclear receptors are popular targets for drugs designed to treat many disorders of those life processes -- from high blood pressure and diabetes to heart disease and cancer.
By studying nuclear receptors in mice, Mangelsdorf (of the University of Texas Southwestern Medical Center at Dallas) and colleagues showed that production of nuclear receptors in the body (about four dozen are known in humans) are remarkably coordinated. Some subgroups of the family are produced at high levels all over the body; other subgroups are found in certain tissues but not others.
Concept from NIEHS
Overall production patterns suggest that nuclear receptors participate in two main networks of activity: one related to reproduction, development and growth, and higher brain function; the other involved in eating food, metabolizing it, and the body's defenses against disease.
In other words, networks of molecular activity are not confined within specific body tissues or organs, but are all part of a network of networks governing the physiological processes of the entire organism.
Survival, after all (as in the battle of the fittest) depends on reproducing, growing and eating (and making efficient use of the food). Nuclear receptors seem to be key players in the meganetwork that ties all these survival functions together. When you add in their role in mental ability and disease immunity, nuclear receptors become indispensable stars of the body's biological show.
Further study of nuclear receptor networks "should lead ultimately to the characterization of the master network that governs the interrelationship of each tissue to the organism as a whole," write Mangelsdorf and co-authors Angie Bookout and Yangsik Jeong (of UT Southwestern) and Michael Downes, Ruth Yu and Ronald Evans of the Salk Institute in La Jolla, Calif.
Understanding that master network will make life's mysteries more solvable and life's miseries more treatable. And it will make it possible to say for sure just how the brain's network of nerve cells knows when to tell the body that it's time to eat.
E-mail: tsiegfried@nasw.org
