Reciprocal Regulation of Brain and Muscle Arnt-Like Protein 1 and Peroxisome Proliferator-Activated Receptor α Defines a Novel Positive Feedback Loop in the Rodent Liver Circadian Clock

Mar 25, 2006Molecular endocrinology (Baltimore, Md.)

Brain and muscle proteins control each other to create a feedback loop in the daily liver clock of rodents

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Abstract

PPARalpha is required to maintain the circadian rhythm of the master clock gene bmal1 in vivo.

  • PPARalpha influences both central and peripheral circadian control mechanisms.
  • It directly binds to a specific region in the promoter of the bmal1 gene.
  • BMAL1 acts as an upstream regulator of PPARalpha gene expression.
  • Fenofibrate can induce a circadian rhythm of clock gene expression in cell culture.
  • Fenofibrate also up-regulates hepatic bmal1 levels in vivo.
  • Findings suggest a regulatory feedback loop between BMAL1 and PPARalpha in peripheral clocks.

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