Time-of-Day Control of Hypoxic Liver Response via BMAL1 and HIF1α

We recently discovered that the circadian clock protein BMAL1 cooperates with the oxygen sensor HIF1α in the liver to regulate the body’s daily response to hypoxia. In animal models lacking both hepatic BMAL1 and HIF1α, the hypoxic response is profoundly disrupted, and the animals exhibit a time-of-day–dependent inability to tolerate low oxygen levels. Unexpectedly, these mice develop a severe pulmonary condition affecting the lung vasculature, closely resembling hepatopulmonary syndrome, a disorder commonly observed in patients with liver disease. This study uncovers a critical role for BMAL1 and HIF1α in liver–lung communication and reveals an essential link between circadian clock regulation and oxygen sensing and signaling. Cell Metabolism, 2024 September 3;36(9):2038-2053