Scientists at Karolinska Institute used an innovative three-dimensional imaging technology to discover that one part of the autonomic nervous system in the liver experiences severe degeneration in non-alcoholic fatty liver disease.
Sympathetic nerves (white) around the portal vein (blue), the bile duct (yellow), and the hepatic artery (red) in the liver. Image Credit: Csaba Adori et al., Science Advances, July 2021.
The study carried out in mice and human liver tissue has illustrated that the degeneration of nerves is associated with the severity of liver pathology. The study findings have been reported in the Science Advances journal.
Non-alcoholic fatty liver disease is the most common hepatic disorder and occurs in 25% of the global population. Nearly one-third of all fatty liver cases lead to steatohepatitis, a severe disease that causes a serious impact on the entire metabolism.
In the latest study, scientists examined the nervous system in the fatty liver with the help of volume immuno-imaging and light-sheet microscopy. This is an innovative imaging method that offers comprehensive large-scale 3D visualization along with cellular resolution. As per the study, this technology can disclose even early, minor, or hidden liver structural impairments.
Now we know that nerves in the liver have multiple subtle regulatory roles. Their role, however, may be more essential during the fight-or-flight response or when subjected to metabolic challenges.
Csaba Adori, Study Lead and Researcher, Department of Neuroscience, Karolinska Institute
“Degeneration of liver sympathetic nerves and abnormal operation of the remaining nerve fibers in the fatty liver could compromise all these functions, which may contribute to further aggravation of the disease, as part of a vicious cycle,” added Adori.
Occurs Already in Early Stages
The study shows that modifications in the liver innervation take place already in the initial stages of fatty liver disease. Hence, with advancement to the more severe steatohepatitis, such impairments become a pronounced degeneration of the nerves.
Moreover, the nerve pathology found in this disease is the same as the one in the mouse model of fatty liver and human fatty liver samples. Currently, the researchers hope that the findings of the study will pave the way for new therapeutic methods in the treatment of portal hypertension and steatohepatitis, by targeting the liver sympathetic nervous system.
The study was financially supported by the Knut and Alice Wallenberg Foundation, the Swedish Research Council, the Sven Mattsson’s Foundation, the Åhlén-Foundation, and the NovoNordisk Foundation. Researchers from SciLifeLab, Karolinska University Hospital, and several universities in Sweden, Slovakia, the United States, and Germany also contributed to the study.
Journal Reference:
Adori, C., et al. (2021) Disorganization and degeneration of liver sympathetic innervations in nonalcoholic fatty liver disease revealed by 3D imaging. Science Advances. doi.org/10.1126/sciadv.abg5733.