Fasting Imparts a Switch to Alternative Daily Pathways in Liver and Muscle

The circadian clock operates as intrinsic time-keeping machinery to preserve homeostasis in response to the changing environment. While food is a known zeitgeber for clocks in peripheral tissues, it remains unclear how lack of food influences clock function. We demonstrate that the transcriptional r...

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Published in:	Cell reports (Cambridge) Vol. 25; no. 12; pp. 3299 - 3314.e6
Main Authors:	Kinouchi, Kenichiro, Magnan, Christophe, Ceglia, Nicholas, Liu, Yu, Cervantes, Marlene, Pastore, Nunzia, Huynh, Tuong, Ballabio, Andrea, Baldi, Pierre, Masri, Selma, Sassone-Corsi, Paolo
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 18.12.2018 Elsevier
Subjects:	Animals circadian Circadian Clocks - genetics Circadian Rhythm - physiology clock CLOCK Proteins - metabolism fasting Fasting - physiology Feeding Behavior Gene Expression Regulation liver Liver - physiology Male metabolism Mice, Inbred C57BL muscle Muscle, Skeletal - physiology Organ Specificity - genetics rhythm RNA-seq Time Factors Transcription Factors - metabolism transcriptome circadian RNA-seq liver transcriptome muscle metabolism fasting clock rhythm
ISSN:	2211-1247, 2211-1247
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Summary:	The circadian clock operates as intrinsic time-keeping machinery to preserve homeostasis in response to the changing environment. While food is a known zeitgeber for clocks in peripheral tissues, it remains unclear how lack of food influences clock function. We demonstrate that the transcriptional response to fasting operates through molecular mechanisms that are distinct from time-restricted feeding regimens. First, fasting affects core clock genes and proteins, resulting in blunted rhythmicity of BMAL1 and REV-ERBα both in liver and skeletal muscle. Second, fasting induces a switch in temporal gene expression through dedicated fasting-sensitive transcription factors such as GR, CREB, FOXO, TFEB, and PPARs. Third, the rhythmic genomic response to fasting is sustainable by prolonged fasting and reversible by refeeding. Thus, fasting imposes specialized dynamics of transcriptional coordination between the clock and nutrient-sensitive pathways, thereby achieving a switch to fasting-specific temporal gene regulation. [Display omitted] •Transcriptional response to fasting is robustly rhythmic in liver and muscle•Lack of food fails to sustain “free-running” conditions of peripheral circadian clocks•Genes are temporally regulated by the clock and fasting-related transcription factors•Rhythmic response to fasting is reversible by refeeding Kinouchi et al. reveal that fasting affects peripheral circadian clocks in the liver and skeletal muscle. Fasting operates by influencing the circadian clock and fasting-sensitive transcription factors, thereby cooperatively achieving fasting-specific temporal gene regulation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 AUTHOR CONTRIBUTIONS K.K., S.M., and P.S.-C. designed the study. K.K. and M.C. conducted the experiments. K.K., C.M., N.C., Y.L., and P.B. performed the bioinformatics analysis. T.H. helped to collect samples. N.P. and A.B. helped in data discussion and project design. K.K., S.M., and P.S.-C. wrote the paper with input from all of the authors.
ISSN:	2211-1247 2211-1247
DOI:	10.1016/j.celrep.2018.11.077