Hepatic neurons and metabolically induced liver dysfunction.
Nat Rev Endocrinol 2026 Jun 19. [Online ahead of print]

Abstract

Hepatic nerves have an underexplored role in liver function. The global prevalence of liver disease has reached unprecedented levels, with over 1.6 billion individuals affected by metabolic dysfunction-associated steatotic liver disease (MASLD). A comprehensive understanding of these liver disease mechanisms is essential for identifying the aetiologies of such conditions. Studies from the past 5 years suggest that hepatic nerves might influence the progression of MASLD to metabolic dysfunction-associated steatohepatitis and hepatocellular carcinoma. As MASLD advances, hepatic sympathetic activity increases while hepatic sympathetic innervation diminishes. Conversely, both parasympathetic and sympathetic innervation might contribute to hepatic fibrosis and liver dysfunction. This Review examines the function of hepatic neurons, their modulation by metabolic disease and the potential to target these mechanisms to develop novel treatments for liver diseases.

Authors+Show Affiliations

Pauss SN0000-0002-7365-7172Drug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA.
Chhabra KHDrug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA. Barnstable Brown Diabetes Center, University of Kentucky College of Medicine, Lexington, KY, USA.
Stec DE0000-0001-8359-4008Department of Physiology & Biophysics, Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, MS, USA.
Gipson CDDrug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA. Barnstable Brown Diabetes Center, University of Kentucky College of Medicine, Lexington, KY, USA.
Hinds TD0000-0002-7599-1529Drug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA. Terry.Hinds@uky.edu. Barnstable Brown Diabetes Center, University of Kentucky College of Medicine, Lexington, KY, USA. Terry.Hinds@uky.edu. Markey Cancer Center, University of Kentucky, Lexington, KY, USA. Terry.Hinds@uky.edu.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

42321413