Rhythmic food intake affects rhythmic gene expression in cells, contrary to previous models
According to the researchers, mammalian cells follow a certain rhythm when it comes to gene expression. This allows them to control the activation of cell- or tissue-specific processes and ensure that they occur at the most appropriate time of the day.
The rhythmic expression of genes is said to be governed by molecular circadian clocks scattered throughout the body. And all of these clocks are synchronized by a pacemaker in a region of the brain called the suprachiasmatic nucleus (SCN).
If one of the molecular clocks becomes out of sync, the SCN employs various cues to put it back in sync. These cues can come in the form of neuronal signaling rhythms, hormone production rhythms, body temperature rhythms, and food intake rhythms.
According to previous models, peripheral circadian clocks, which are present in nearly every tissue and organ, regulate rhythmic gene expression cell-autonomously -- that is, independently inside each cell. However, the researchers found that rhythmic food intake heavily influences rhythmic gene expression independently of the peripheral clock in the liver.
The timing of food intake regulates many metabolic pathways
In an attempt to discover the exact role of food intake timing in circadian biology and the rhythmic expression of genes, the researchers designed an experiment using mice. They varied the feeding times of two different groups to follow either an arrhythmic pattern (food intake restricted to nighttime only) or an unrestricted pattern. The experiment lasted for five weeks, after which the researchers collected the animals' livers at various points during the day to study the expression of genes in the liver.
The researchers found that arrhythmic feeding disrupted the rhythmicity of the expression of 70 percent of cycling mouse liver genes. This disruption only affected genes that don't belong to the core clock present in mouse liver. The core clock genes, meanwhile, retained their rhythmic expression despite the arrhythmic feeding pattern.
In addition, the researchers also found that the timing of food intake alters the timing of key signaling and metabolic pathways without affecting the oscillations of the core clock in the liver. Some of the pathways affected by feeding time are involved in the production of cholesterol and glycogen, the main storage form of glucose.
Based on these findings, the researchers concluded: “The systemic signals driven by rhythmic food intake significantly contribute to driving rhythms in liver gene expression and metabolic functions independently of the cell-autonomous hepatic clock.”
Jerome Menet, one of the authors of the study, further explains that the importance of feeding time extends beyond just synchronizing the molecular clock in different organs; it regulates rhythmic gene expression in parallel of the clock. (Related: Diet plans need to be made based on meal timing, not calorie intake.)
“This raises the interesting hypothesis that eating at the wrong time of the day, which is prevalent in shift-workers for example, can desynchronize rhythmic gene expression and lead to pathologies,” he added.
Disruptions in the human circadian clocks are said to be linked to many biological events, such as aging, the development of chronic diseases, and altered responses to medications. The researchers believe that controlling the timing of your food intake may help delay or prevent these events. However, since the experiment was conducted on mouse tissue, the results of the study still need to be validated by human studies before their implications on human health are fully accepted.
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