Physiological significance of a peripheral tissue circadian clock

Mammals have circadian clocks in peripheral tissues, but there is no direct evidence of their physiological importance. Unlike the suprachiasmatic nucleus clock that is set by light and drives rest-activity and fasting-feeding cycles, peripheral clocks are set by daily feeding, suggesting that at le...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-09, Vol.105 (39), p.15172-15177
Main Authors: Lamia, Katja A, Storch, Kai-Florian, Weitz, Charles J
Format: Article
Language:English
Subjects:
Animals
ARNTL Transcription Factors
Basic Helix-Loop-Helix Transcription Factors - genetics
Basic Helix-Loop-Helix Transcription Factors - physiology
Biological Sciences
Blood glucose
Body tissues
Circadian rhythm
Circadian Rhythm - genetics
Circadian Rhythm - physiology
Fasting
Gene expression
Gene Expression Regulation
Genes
Genotypes
Glucose
Glucose - metabolism
Homeostasis
Homeostasis - genetics
Insulin
Liver
Liver - metabolism
Liver - physiology
Metabolism
Mice
Mice, Mutant Strains
Physiology
Tissues
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Summary:Mammals have circadian clocks in peripheral tissues, but there is no direct evidence of their physiological importance. Unlike the suprachiasmatic nucleus clock that is set by light and drives rest-activity and fasting-feeding cycles, peripheral clocks are set by daily feeding, suggesting that at least some contribute metabolic regulation. The liver plays a well known role in glucose homeostasis, and we report here that mice with a liver-specific deletion of Bmal1, an essential clock component, exhibited hypoglycemia restricted to the fasting phase of the daily feeding cycle, exaggerated glucose clearance, and loss of rhythmic expression of hepatic glucose regulatory genes. We conclude that the liver clock is important for buffering circulating glucose in a time-of-day-dependent manner. Our findings suggest that the liver clock contributes to homeostasis by driving a daily rhythm of hepatic glucose export that counterbalances the daily cycle of glucose ingestion resulting from the fasting-feeding cycle.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0806717105