Hepatic BMAL1 and HIF1α regulate a time-dependent hypoxic response and prevent hepatopulmonary-like syndrome

The majority of the transcriptional response to hypoxia is dependent on either Bmal1 or Hif1α.

• Bmal1 and Hif1α play shared and distinct roles in the circadian response to hypoxia.
• Hypoxia-inducible factor HIF1α accumulation is regulated by time and is dependent on Bmal1.
• Mice lacking both hepatic Bmal1 and Hif1α exhibit hypoxemia and increased mortality when exposed to hypoxia, with effects varying by time of day.
• These mice show mild liver dysfunction and pulmonary vasodilation, linked to specific signaling pathways.
• The findings suggest that hepatic BMAL1 and HIF1α are critical regulators of the hypoxic response.

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