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Neural connections between the hypothalamus and the liver

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Uyama, Naoki, Geerts, Albert, Reynaert, Hendrik·2004·The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology
DOI 10.1002/ar.a.20086
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Abstract

After receiving information from afferent nerves, the hypothalamus sends signals to peripheral organs, including the liver, to keep homeostasis. There are two ways for the hypothalamus to signal to the peripheral organs: by stimulating the autonomic nerves and by releasing hormones from the pituitary gland. In order to reveal the involvement of the autonomic nervous system in liver function, we focus in this study on autonomic nerves and neuroendocrine connections between the hypothalamus and the liver. The hypothalamus consists of three major areas: lateral, medial, and periventricular. Each area has some nuclei. There are two important nuclei and one area in the hypothalamus that send out the neural autonomic information to the peripheral organs: the ventromedial hypothalamic nucleus (VMH) in the medial area, the lateral hypothalamic area (LHA), and the periventricular hypothalamic nucleus (PVN) in the periventricular area. VMH sends sympathetic signals to the liver via the celiac ganglia, the LHA sends parasympathetic signals to the liver via the vagal nerve, and the PVN integrates information from other areas of the hypothalamus and sends both autonomic signals to the liver. As for the afferent nerves, there are two pathways: a vagal afferent and a dorsal afferent nerve pathway. Vagal afferent nerves are thought to play a role as sensors in the peripheral organs and to send signals to the brain, including the hypothalamus, via nodosa ganglia of the vagal nerve. On the other hand, dorsal afferent nerves are primary sensory nerves that send signals to the brain via lower thoracic dorsal root ganglia. In the liver, many nerves contain classical neurotransmitters (noradrenaline and acetylcholine) and neuropeptides (substance P, calcitonin gene‐related peptide, neuropeptide Y, vasoactive intestinal polypeptide, somatostatin, glucagon, glucagon‐like peptide, neurotensin, serotonin, and galanin). Their distribution in the liver is species‐dependent. Some of these nerves are thought to be involved in the regulation of hepatic function as well as of hemodynamics. In addition to direct neural connections, the hypothalamus can affect metabolic functions by neuroendocrine connections: the hypothalamus‐pancreas axis, the hypothalamus‐adrenal axis, and the hypothalamus‐pituitary axis. In the hypothalamus‐pancreas axis, autonomic nerves release glucagon and insulin, which directly enter the liver and affect liver metabolism. In the hypothalamus‐adrenal axis, autonomic nerves release catecholamines such as adrenaline and noradrenaline from the adrenal medulla, which also affects liver metabolism. In the hypothalamus‐pituitary axis, release of glucocorticoids and thyroid hormones is stimulated by pituitary hormones. Both groups of hormones modulate hepatic metabolism. Taken together, the hypothalamus controls liver functions by neural and neuroendocrine connections. © 2004 Wiley‐Liss, Inc.

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  • The central brain-endocrine crosstalk, mainly the glucosensor-hypothalamus-liver-pancreas link, modifies peripheral GIG interactions to control brain glucose homeostasis.

    “The latter, mainly consisting of the glucosensor-hypothalamus-liver-pancreas link [17,30], modifies the peripheral GIG interactions in order to control brain glucose homeostasis, as shown in Fig. 1.”

    From A mathematical model of brain glucose homeostasis (2009) · cites this paper as [17]

    The section on indirect autonomic pathways (page unavailable) describes hypothalamic signals acting through the pancreas to release insulin and glucagon, which regulate glucose homeostasis and affect liver metabolism. It does not describe a glucosensor–hypothalamus–liver–pancreas link modifying peripheral GIG interactions to control glucose homeostasis specifically in the brain. (LLM, conf=0.86)

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  • The framework corresponding to feedback control of brain glucose homeostasis is supported by anatomical evidence.

    “Such a framework corresponding to feedback control of brain glucose homeostasis is supported by anatomical evidences.”

    From A mathematical model of brain glucose homeostasis (2009) · cites this paper as [17]

    The Afferent Nerves From Liver section describes nerves that may sense circulating glucose, while the Efferent Nerves section describes a hypothalamus-to-liver pathway that affects glucose output. Together, these provide anatomical support for a feedback framework, but the paper addresses hepatic and systemic glucose regulation rather than specifically demonstrating feedback control of brain glucose homeostasis. Page numbers were not available in our copy. (LLM, conf=0.82)

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  • After receiving information from afferent nerves, the hypothalamus sends signals, by stimulating autonomic nerves or by releasing hormones from the pituitary gland, to peripheral organs, including the liver and pancreas, to maintain homeostasis.

    “After receiving information (central and peripheral glucose, central insulin) from afferent nerves, the hypothalamus sends signals, by stimulating the autonomic nerves or by releasing hormones from the pituitary gland, to the peripheral organs, including the liver and pancreas, to maintain homeostasis [17].”

    From A mathematical model of brain glucose homeostasis (2009) · cites this paper as [17]

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Authors
Uyama, N., Geerts, A., & Reynaert, H.
Affiliations
Vrije Universiteit Brussel (BE)
Corresponding author
Uyama, Naoki
ORCID
Reynaert, Hendrik
Venue
The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology
Publisher
Wiley
Published
2004-08-24
Volume
280A
Issue
1
Pages
808-820
ISSN
  • 1552-4884 (ISSN-L)
  • 1552-4892
DOI
10.1002/ar.a.20086
OpenAlex
W2052528853
Cited by
201
References
138
Citations by year
2026: 9 · 2025: 6 · 2024: 16 · 2023: 15 · 2022: 9 · 2021: 7 · 2020: 6 · 2019: 6 · 2018: 6 · 2017: 9 · 2016: 4 · 2015: 7 · 2014: 11 · 2013: 14 · 2012: 10
FWCI
1.01
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The Anatomical Record Part A Discoveries in Molecular Cellular and Evolutionary Biology (publishedVersion)
  • PubMed (publishedVersion)
  • VUBIR (Vrije Universiteit Brussel) (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords
autonomic nervous system, neuroendocrine regulation, ventromedial hypothalamus, lateral hypothalamus, vagal afferent nerves, hepatic innervation, neuropeptides, hypothalamic-pituitary axis, hepatic hemodynamics, hepatic glucose metabolism, hepatic lipogenesis
MeSH terms
Adrenal Glands, Glucose, Humans, Hypothalamus, Liver, Neural Pathways, Neuropeptides, Neurosecretory Systems, Pancreas, Autonomic Pathways

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