Circadian Clocks Are Resounding in Peripheral Tissues

Circadian rhythms are prevalent in most organisms. Even the smallest disturbances in the orchestration of circadian gene expression patterns among different tissues can result in functional asynchrony, at the organism level, and may to contribute to a wide range of physiologic disorders. It has been reported that as many as 5%–10% of transcribed genes in peripheral tissues follow a circadian expression pattern. We have conducted a comprehensive study of circadian gene expression on a large dataset representing three different peripheral tissues. The data have been produced in a large-scale microarray experiment covering replicate daily cycles in murine white and brown adipose tissues as well as in liver. We have applied three alternative algorithmic approaches to identify circadian oscillation in time series expression profiles. Analyses of our own data indicate that the expression of at least 7% to 21% of active genes in mouse liver, and in white and brown adipose tissues follow a daily oscillatory pattern. Indeed, analysis of data from other laboratories suggests that the percentage of genes with an oscillatory pattern may approach 50% in the liver. For the rest of the genes, oscillation appears to be obscured by stochastic noise. Our phase classification and computer simulation studies based on multiple datasets indicate no detectable boundary between oscillating and non-oscillating fractions of genes. We conclude that greater attention should be given to the potential influence of circadian mechanisms on any biological pathway related to metabolism and obesity.Synopsis: The metabolism of living organisms changes over the twenty-four hour daily cycle in an oscillatory manner. This repeating pattern of “peak” and “trough” expression is known as a “circadian rhythm.” We now know that the body's internal clock is controlled by a discrete group of genes. These important regulators are found in many different organs of the body, and they control expression of many other genes in the body. Using mice as an experimental animal, Ptitsyn and colleagues looked at the overall pattern of gene expression in fat tissues and the liver using three different mathematical tests. They present data indicating that the majority of active genes fluctuate rhythmically over a twenty-four hour period. This work suggests that future studies should pay close attention to the influence of the circadian rhythm in obesity and in fat metabolism.