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

Kenichiro Kinouchi, Christophe Magnan, Nicholas Ceglia, Yu Liu, Marlene Cervantes, Nunzia Pastore, Tuong Huynh, Andrea Ballabio, Pierre Baldi, Selma Masri, Paolo Sassone-Corsi

研究成果: Article査読

49 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)3299-3314.e6
ジャーナルCell Reports
25
12
DOI
出版ステータスPublished - 2018 12 18
外部発表はい

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学(全般)

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