Gad Asher

Organization and specificity of the peripheral circadian clock system

Gad Asher

The mammalian circadian system consists of a central clock in the brain that synchronizes clocks in peripheral tissues. While the hierarchy between the central and peripheral clocks is established, little is known regarding the specificity and functional organization of peripheral clocks. Here, we employed feeding paradigms in conjunction with liver-clock mutant mice, to map disparities and interactions between peripheral rhythms. We found that peripheral clocks largely differ in their response to feeding-time. In view of the liver’s prominent role in nutrient processing, we hypothesized that the liver-clock instigates the response of peripheral clocks to feeding. The liver-clock, however, did not affect rhythmicity of clocks in other peripheral tissues. Yet, unexpectedly, it strongly modulated their transcriptional rhythmicity upon daytime feeding. Concomitantly, liver-clock mutant mice exhibited impaired glucose and lipid homeostasis, which were aggravated by daytime feeding. Overall, our findings suggest that upon nutrient challenge the liver-clock buffers the effect of feeding-related signals on rhythmicity of peripheral tissues, irrespective of their clocks.