SEARCHNARRATIVE_REVIEWgastroenterology, endocrinology

narrative_review·gastroenterology, endocrinology, preclinical research, immunology·PMC10348844

Hepatic Innervations and Nonalcoholic Fatty Liver Disease

Seminars in Liver Disease · 7 authors, 7 centres

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TL;DR

The authors report that chronic sympathetic overactivity drives steatosis through increased free fatty acid uptake and de novo lipogenesis, while sympathetic denervation reversed high-fat diet-induced steatosis in mice.

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narrative_review

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gastroenterology

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ORIGINAL PAPER

PMC10348844

Hepatic Innervations and Nonalcoholic Fatty Liver Disease

Seminars in Liver Disease

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ABSTRACT

Abstract 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. Keywords: nonalcoholic fatty liver disease, sympathetic nerves, parasympathetic nerves, noradrenaline, steatosis, inflammation, fibrosis, portal hypertension

CITATION EXPORT

Monika Adori, Sadam Bhat, Roberto Gramignoli et al.. Hepatic Innervations and Nonalcoholic Fatty Liver Disease. Seminars in Liver Disease. (2023). https://doi.org/10.1055/s-0043-57237

AUTHORS

7 · 7 CENTRES

Monika Adori, Sadam Bhat, Roberto Gramignoli, Ismael Valladolid-Acebes, Tore Bengtsson, Mathias Uhlèn, Csaba Adori

1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
2Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
3Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
4Department of Molecular Medicine and Surgery, The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden
5Department of Molecular Biosciences, The Wenner-Gren Institute (MBW), Stockholm University, Stockholm, Sweden
6Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
7Science for Life Laboratory, Royal Institute of Technology, Stockholm, Sweden