TY - JOUR
T1 - The liver-clock coordinates rhythmicity of peripheral tissues in response to feeding
AU - Manella, Gal
AU - Sabath, Elizabeth
AU - Aviram, Rona
AU - Dandavate, Vaishnavi
AU - Ezagouri, Saar
AU - Golik, Marina
AU - Adamovich, Yaarit
AU - Asher, Gad
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/6
Y1 - 2021/6
N2 - The mammalian circadian system consists of a central clock in the brain that synchronizes clocks in the peripheral tissues. Although the hierarchy between central and peripheral clocks is established, little is known regarding the specificity and functional organization of peripheral clocks. Here, we employ altered feeding paradigms in conjunction with liver-clock mutant mice to map disparities and interactions between peripheral rhythms. We find that peripheral clocks largely differ in their responses to feeding time. Disruption of the liver-clock, despite its prominent role in nutrient processing, does not affect the rhythmicity of clocks in other peripheral tissues. Yet, unexpectedly, liver-clock disruption strongly modulates the transcriptional rhythmicity of peripheral tissues, primarily on daytime feeding. Concomitantly, liver-clock mutant mice exhibit impaired glucose and lipid homeostasis, which are 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.
AB - The mammalian circadian system consists of a central clock in the brain that synchronizes clocks in the peripheral tissues. Although the hierarchy between central and peripheral clocks is established, little is known regarding the specificity and functional organization of peripheral clocks. Here, we employ altered feeding paradigms in conjunction with liver-clock mutant mice to map disparities and interactions between peripheral rhythms. We find that peripheral clocks largely differ in their responses to feeding time. Disruption of the liver-clock, despite its prominent role in nutrient processing, does not affect the rhythmicity of clocks in other peripheral tissues. Yet, unexpectedly, liver-clock disruption strongly modulates the transcriptional rhythmicity of peripheral tissues, primarily on daytime feeding. Concomitantly, liver-clock mutant mice exhibit impaired glucose and lipid homeostasis, which are 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.
UR - http://www.scopus.com/inward/record.url?scp=85107296802&partnerID=8YFLogxK
U2 - 10.1038/s42255-021-00395-7
DO - 10.1038/s42255-021-00395-7
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C2 - 34059820
AN - SCOPUS:85107296802
SN - 2522-5812
VL - 3
SP - 829
EP - 842
JO - Nature Metabolism
JF - Nature Metabolism
IS - 6
ER -