The Body Clock and HIF1α Work Together to Control Oxygen Use and Sugar Breakdown in Skeletal Muscle

Genetic disruption of the clock activator BMAL1 in skeletal myotubes and fibroblasts increased levels of hypoxia-inducible factor 1α (HIF1α) under hypoxic conditions.

• Disruption of BMAL1 decreased anaerobic glycolysis and mitochondrial respiration in muscle cells and fibroblasts.
• The absence of BMAL1 led to reduced transcription of HIF1α target genes involved in responding to low oxygen.
• Clock repressors CRY1/2 influenced HIF1α stability during hypoxia, suggesting a regulatory role in this process.
• HIF1α directly interacted with core clock gene promoters, indicating a connection between oxygen sensing and circadian rhythms.
• Exercise-induced expression of clock and HIF1α target genes varied depending on the time of day in normal mice.

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