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Disorganization and degeneration of liver sympathetic innervations in nonalcoholic fatty liver disease revealed by 3D imaging
Karolinska Inst, Sweden.
Karolinska Inst, Sweden.
Karolinska Inst, Sweden.
Karolinska Inst, Sweden.
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2021 (English)In: Science Advances, E-ISSN 2375-2548, Vol. 7, no 30, article id eabg5733Article in journal (Refereed) Published
Abstract [en]

Hepatic nerves have a complex role in synchronizing liver metabolism. Here, we used three-dimensional (3D) immunoimaging to explore the integrity of the hepatic nervous system in experimental and human nonalcoholic fatty liver disease (NAFLD). We demonstrate parallel signs of mild degeneration and axonal sprouting of sympathetic innervations in early stages of experimental NAFLD and a collapse of sympathetic arborization in steatohepatitis. Human fatty livers display a similar pattern of sympathetic nerve degeneration, correlating with the severity of NAFLD pathology. We show that chronic sympathetic hyperexcitation is a key factor in the axonal degeneration, here genetically phenocopied in mice deficient of the Rac-1 activator Vav3. In experimental steatohepatitis, 3D imaging reveals a severe portal vein contraction, spatially correlated with the extension of the remaining nerves around the portal vein, enlightening a potential intrahepatic neuronal mechanism of portal hypertension. These fundamental alterations in liver innervation and vasculature uncover previously unidentified neuronal components in NAFLD pathomechanisms.

Place, publisher, year, edition, pages
American Association for the Advancement of Science , 2021. Vol. 7, no 30, article id eabg5733
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-178528DOI: 10.1126/sciadv.abg5733ISI: 000675849000005PubMedID: 34290096OAI: oai:DiVA.org:liu-178528DiVA, id: diva2:1587744
Note

Funding Agencies|Swedish Research CouncilSwedish Research CouncilEuropean Commission [04X-2887]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation; Sven Mattssons Foundation; Ahlen-Foundation; NovoNordisk postdoctoral Fellowship

Available from: 2021-08-25 Created: 2021-08-25 Last updated: 2021-09-21

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