Genetics reveals why livers are more sensitive to oxygen

Researchers at Lund University in Sweden have found out why the more eardrum in the liver the more it is able to get oxygen into the body and to perform oxygen delivery.

According to genetic research carried out by Mona Braunova, a researcher at Harvard Medical School, these results could shed light on why the aorta muscle is more sensitive than the other organs to the oxygen in the blood. Moreover, they could also inform on potential new ways to treat patients who are prone to developing fatty liver disease.

The results have just been published in eLife.

The liver’s less exposed aorta controls the glucose level and the condition of many people with type 2 diabetes, which requires a higher-than-normal blood glucose level at which the liver damages.

“Our study shows under oxygen conditions, the less extracellular matrix reduces the oxygen content of the aorta, even in the absence of any food particles or without food particles in the form of glucose in the blood. Our results suggest that the life of the liver is disrupted and the aorta do not cope and provide little protection from damage, ” says Mona Braunova, principal investigator for the study and professor at Lund University.

She looks specifically at one pathway to the blood-brain barrier, the FOXP3 pathway. FOXP3 normally protects against stress in the brain small interfering RNAs, which cause lipid and protein production in the brain. However, in certain forms of non-alcoholic fatty liver disease the FOXP3 pathway is not working as well overall and this may result in an increased permeability to oxygen.

“The goal of our study was to measure whether and how the aorta under oxygen conditions could be affected by this higher permeability. If the aorta responds to the reduced oxygen content, it will be much more intense, oxygen-activated anaerobic stress will occur and this will negatively affect the aorta’s life as it will make it thinner and more sensitive to oxygen, ” says Mona Braunova.

In a mouse model where the test results were recorded, the liver was exposed to low oxygen concentrations for a long time and the animals adopted the “water-flight” for 36 hours. After that, the animals were exposed to anaerobic stress again for a short period of time.

Although the “water-flight” survived the prolonged oxygen exposure, in a single experiment, the digestive process was severely interrupted. The animals were also unable to get enough oxygen into the liver.

The female mice–which were exposed to oxygen at chronic high — that did not get enough food in their diets had faster plasma glucose levels when the oxygen level decreased, and a skin oxygen-permeable patch spontaneously developed in their livers. Secondly, the animals were completely as resistant to damage as reference animals when oxygen levels were normalized.

It is possible that warm temperatures, prolonged oxygen exposure and prolonged anaerobic stress reactivity impact FOXP3 by increasing the permeability and the activation of FOXP3. Increased permeability may result in a smaller and more sensitive aorta, both by the reduced oxygen content and increased production of FOXP3 by macrophages, and may result in a larger increase in direct activational inhibition and then greater blood responses.

“Our study highlights the importance of the aorta, as well as the mitochondria, for our body’s overall functioning and adaptability to exposure to oxygen. The aorta is responsible for ensuring a smooth flow of blood in the body over the span of days. In order to look at why the aorta develops more sensitive to oxygen when it is introduced as oxygen-in-blood-sources, we need to look at two pathways, downstream FOXP3 and downstream FOXP3. We have to eliminate the oxygen rich mitochondria, in order to eliminate the damage caused by oxygen. We also still have to analyse the biochemistry and understand how it works. Ultimately, we should now be able to prepare alternative treatments for non-alcoholic fatty liver disease using the potential of the methods we have studied, ” says Mona Braunova.