CLOCK/BMAL1 regulates circadian change of mouse hepatic insulin sensitivity by SIRT1

Knockdown of CLOCK or BMAL1 induces hepatic insulin resistance in mice.

• CLOCK and BMAL1, core circadian transcription factors, correlate with hepatic insulin sensitivity.
• Ectopic expression of CLOCK or BMAL1 reduces hepatic insulin resistance.
• Circadian changes in insulin sensitivity are impaired in mice with mutations in Clock or liver-specific knockouts of Bmal1 or Sirt1.
• CLOCK and BMAL1 are necessary for the circadian expression of the protein deacetylase SIRT1.
• Circadian misalignment in mice, induced by constant darkness, decreases levels of hepatic BMAL1 and SIRT1, leading to insulin resistance.
• Resveratrol treatment can reverse insulin resistance caused by circadian misalignment.

AI simplified