A groundbreaking discovery from the Weizmann Institute of Science has shed light on the mysterious timing of health conditions like asthma and heart attacks. The study, from Prof. Gad Asher’s laboratory at the Weizmann Institute of Science’s Biomolecular Sciences Department and published in Cell Metabolism, reveals that a key component of our circadian clock regulates our body’s response to oxygen. This finding offers a potential explanation for why these conditions often strike in the early morning hours.
Researchers from Asher’s lab, which for years has been studying the connection between metabolism and circadian clocks, had previously discovered that liver tissue responds differently to oxygen shortage at different times of the day. To deepen their understanding of the relationship between oxygen, liver tissue and the circadian clocks, they created three groups of genetically engineered mice that could not produce either one or both of the above-mentioned proteins in their liver tissue: The first group did not produce HIF-1α, the protein that regulates the response to oxygen deficiency; the second group did not produce BMAL1, the key component of the circadian clock; and the third one did not produce either of them. The researchers then examined what happened to each group when oxygen levels were reduced. They found that, in the absence of BMAL1, the HIF-1α protein failed to accumulate as it does in a normal response to oxygen shortage. Moreover, they discovered that these two proteins – separately and together – are largely responsible for activating the genetic response needed to deal with oxygen shortage.
“The mechanism we discovered, which combines both proteins, is probably the main mechanism by which mammals cope with oxygen deficiency,” says Asher. “These and other findings helped us understand that the circadian clock not only responds to oxygen deficiency, as was already known, but that it actually activates the body’s mechanism for dealing with oxygen deficiency.”
A groundbreaking study has revealed a surprising link between liver disease and lung function. Researchers at the Weizmann Institute of Science discovered that mice lacking both HIF-1α and BMAL1 in their livers exhibited low blood oxygen levels and signs of hepatopulmonary syndrome. This suggests that liver dysfunction can lead to lung damage, a condition known as hepatopulmonary syndrome. This novel mouse model offers a valuable tool for understanding the mechanisms underlying this complex disease and developing potential treatments.
“We identified increased production of nitric oxide in the lungs, which causes the blood vessels to dilate. As a result, blood flows through the lungs much more quickly and does not supply oxygen efficiently,” Asher adds. “We still do not know through which mechanisms the liver damage affects lung function, but the initial findings from our genetic mouse model point to an interesting group of proteins that could be part of the communication between the liver and the lungs. In mice that developed the hepatopulmonary syndrome, this communication was disrupted. If these proteins are also produced in human patients and are indeed connected to the syndrome, they might serve as a target for a future therapy.”
