CC BY-NC-ND 4.0 · Semin Liver Dis 2023; 43(02): 149-162
DOI: 10.1055/s-0043-57237
Review Article

Hepatic Innervations and Nonalcoholic Fatty Liver Disease

Monika Adori
1   Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
Sadam Bhat
2   Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
Roberto Gramignoli
3   Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
Ismael Valladolid-Acebes
4   Department of Molecular Medicine and Surgery, The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden
Tore Bengtsson
5   Department of Molecular Biosciences, The Wenner-Gren Institute (MBW), Stockholm University, Stockholm, Sweden
Mathias Uhlèn
6   Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
7   Science for Life Laboratory, Royal Institute of Technology, Stockholm, Sweden
Csaba Adori
5   Department of Molecular Biosciences, The Wenner-Gren Institute (MBW), Stockholm University, Stockholm, Sweden
6   Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
› Author Affiliations


Abbreviations graphical abstract: VMN/PVN, hypothalamic ventromedial nucleus/paraventricular nucleus; VLM/VMM, ventrolateral medulla/ventromedial medulla; SMG/CG, superior mesenteric ganglion/caeliac ganglia; NTS, nucleus of the solitary tract; NG, nodose ganglion.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder. Increased sympathetic (noradrenergic) nerve tone has a complex role in the etiopathomechanism of NAFLD, affecting the development/progression of steatosis, inflammation, fibrosis, and liver hemodynamical alterations. Also, lipid sensing by vagal afferent fibers is an important player in the development of hepatic steatosis. Moreover, disorganization and progressive degeneration of liver sympathetic nerves were recently described in human and experimental NAFLD. These structural alterations likely come along with impaired liver sympathetic nerve functionality and lack of adequate hepatic noradrenergic signaling. Here, we first overview the anatomy and physiology of liver nerves. Then, we discuss the nerve impairments in NAFLD and their pathophysiological consequences in hepatic metabolism, inflammation, fibrosis, and hemodynamics. We conclude that further studies considering the spatial-temporal dynamics of structural and functional changes in the hepatic nervous system may lead to more targeted pharmacotherapeutic advances in NAFLD.

Publication History

Article published online:
08 May 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (

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