ArticlePLoS biology2024
The development of hepatic steatosis depends on the presence of liver-innervating parasympathetic cholinergic neurons in mice fed a high-fat diet.
Article in PLoS biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed.
- Hepatic neurons and metabolically induced liver dysfunction.Nature reviews. Endocrinology · 2026Review
- Hypothalamic Control of Liver Health and Disease: From Circuits to Pathophysiology and Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Integrating bulk and single-cell RNA sequencing with GWAS reveals regulatory networks underpinning complex traits in beef cattle.Journal of animal science and biotechnology · 2026Article
- Optogenetic activation of liver-innervating vagal sensory neurons increases anxiety-like behavior in mice.Translational psychiatry · 2026Article
- Brunner's Glands in the Duodenal Bulb Are Indirectly Innervated by Vagal Preganglionics That Connect With Cholinergic Enteric Neurons in the Myenteric Plexus.The Journal of comparative neurology · 2026Article
- From Adipose Dysfunction to Multi-Organ Steatosis: Defining the Metabolic Steatotic Axis.Current issues in molecular biology · 2026Review
- Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Role of central and peripheral serotonin in liver physiology and diseases.Theranostics · 2026Review
- Interaction Between Photoperiod and Sex on Hepatic Lipid Homeostasis in Rats Fed an Obesogenic Diet.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Liver Innervation in Health and Disease: Neuroimmune-Neurovascular Interface and Future Therapeutic Implications.Biomedicines · 2025Review
- Human liver and pancreas innervation: resolving 3D neurohistological challenges and advancing insights.Journal of biomedical science · 2025Review
- Does the liver talk to the brain? If so, how and why?PLoS biology · 2025Article
- Molecular and functional diversity of the autonomic nervous system.Nature reviews. Neuroscience · 2025Review
- Direct vagal input to the gastrointestinal tract and other viscera: Re-definition of autonomic neuroscience or experimental artifacts?Autonomic neuroscience : basic & clinical · 2025Review
- Liver-innervating vagal sensory neurons are indispensable for the development of hepatic steatosis and anxiety-like behavior in diet-induced obese mice.Nature communications · 2025Article
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6 authors.
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Abstract
Hepatic lipid metabolism is regulated by the autonomic nervous system of the liver, with the sympathetic innervation being extensively studied, while the parasympathetic efferent innervation is less understood despite its potential importance. In this study, we investigate the consequences of disrupted brain-liver communication on hepatic lipid metabolism in mice exposed to obesogenic conditions. We found that a subset of hepatocytes and cholangiocytes are innervated by parasympathetic nerve terminals originating from the dorsal motor nucleus of the vagus. The elimination of the brain-liver axis by deleting parasympathetic cholinergic neurons innervating the liver prevents hepatic steatosis and promotes browning of inguinal white adipose tissue (ingWAT). The loss of liver-innervating cholinergic neurons increases hepatic Cyp7b1 expression and fasting serum bile acid levels. Furthermore, knockdown of the G protein-coupled bile acid receptor 1 gene in ingWAT reverses the beneficial effects of the loss of liver-innervating cholinergic neurons, leading to the reappearance of hepatic steatosis. Deleting liver-innervating cholinergic neurons has a small but significant effect on body weight, which is accompanied by an increase in energy expenditure. Taken together, these data suggest that targeting the parasympathetic cholinergic innervation of the liver is a potential therapeutic approach for enhancing hepatic lipid metabolism in obesity and diabetes.
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