Timed secreted proteomes reveal regulation of hepatokines by the liver circadian clock

Jun 2, 2026Nature communications

Timed release of liver proteins shows how the liver’s daily clock controls hormone-like signals

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Abstract

The liver secretes more endostatin during the inactive, fasting phase of the diurnal cycle.

  • Hundreds of proteins are identified that show time-of-day-dependent secretion related to various bodily functions.
  • The secretion of endostatin, derived from collagen type XVIII alpha 1, increases during fasting.
  • Loss of Bmal1 disrupts the regulation of COL18A1 and endostatin levels through changes in gene expression and protein processing.
  • Endostatin may suppress mitochondrial gene expression and respiration in white adipose tissue while promoting lipolysis.
  • These findings suggest a mechanism where endostatin from the liver influences metabolic processes in adipose tissue during fasting.

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