By investigating how animals can predict the timing of food availability, researchers have identified the first gene critical for anticipation of mealtime. This gene, called Period 2, is a key component of the circadian time-keeping system. The findings are reported by Urs Albrecht of the University of Fribourg and Etienne Challet of the University Louis Pasteur/CNRS and colleagues in the October 24th issue of the journal Current Biology, published by Cell Press.
A daily scheduled meal is a potent time-giving cue that can reset the physiological timing of most organs, including the liver. In terms of animal behavior, a daily scheduled meal elicits anticipatory bouts of locomotor activity and changes in body temperature. These food-anticipatory behaviors are believed to be under the control of a food-entrainable mechanism--that is, a timing mechanism within the body that is set by food intake--but how this mechanism works at the molecular level is unknown.
In the new work, the researchers have found the first evidence that a single gene mutation can render mice totally unable to predict the time of food availability. Studying mice, they found that this lack of food anticipation at both behavioral and physiological levels is specifically associated with a mutation in the Period 2 gene, a gene that previous work had shown to play an important role in the brain's ability to run its central circadian clock according to daylight.
The researchers found that, interestingly, synchronization of timing between organs by scheduled meals is not affected by the Period 2 mutation, indicating that this gene is not crucial for scheduled food availability to affect the physiological coordination of tissues outside the central nervous system.
The authors of the study point out that the work they report provides a tool for investigating the brain's cerebral clockwork responsible for predicting mealtime--with this tool in hand, it will be possible to anatomically localize areas of the brain that are involved in food anticipation. Looking forward, the researchers expect that this will allow the study of how these areas interact with other brain regions responsible for other types of behavior, such as learning, memory, and the experience of pleasure.
Knowledge of the mechanism of synchronizing an organism's physiology to mealtime is expected to improve therapies for counteracting disorders that have their roots in a disturbed circadian system, such as sleep problems, eating disorders, obesity, and depression.
The researchers include Céline A. Feillet of University Louis Pasteur and Centre National de la Recherche Scientifique in Strasbourg, France and University of Fribourg in Fribourg, Switzerland; Jürgen Ripperger, Abdul Dulloo, and Urs Albrecht of University of Fribourg in Fribourg, Switzerland; Maria Chiara Magnone of University of Fribourg in Fribourg, Switzerland and Antoine Marxer Institute for Biomedical Research in Ivrea, Italy; Etienne Challet of University Louis Pasteur and Centre National de la Recherche Scientifique in Strasbourg, France.
Support for this study was provided in part by Swiss-French Funds "Programme d'actions intégrées Germaine de Staël" (U.A. and E.C.), the Swiss National Science Foundation, the State of Fribourg and Entrainment of the circadian clock (U.A.), and the Centre National de la Recherche Scientifique (E.C.).
Feillet et al.: "Lack of Food Anticipation in Per2 Mutant Mice." Publishing in Current Biology 16, 2016–2022, October 24, 2006 DOI 10.1016/j.cub.2006.08.053. www.current-biology.com