Hepatic Nervous System and Neurobiology of the Liver

Jensen, Kendal; Alpini, Gianfranco; Glaser, Shannon

doi:10.1002/cphy.c120018

Cited by 143 publications

(151 citation statements)

References 101 publications

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“…Similarly, within hepatic parenchyma such an increase of innervation may impair blood supply within the sinusoidal area and also could have an impact on hepatocyte metabolism; the activity of Kupffer cells and hepatic stellate cells [20]. Sympathetic regulation within the parenchyma of hepatic lobules is not only involved with the regulation of liver physiology, but it could also be related with several pathophysiological processes such as liver repair and regeneration [21].…”

Section: Discussionmentioning

confidence: 99%

Alterations in porcine intrahepatic sympathetic nerves after bisphenol A administration

Thoene

Godlewski

Rytel

et al. 2018

Folia Histochem Cytobiol.

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Introduction. Bisphenol A (BPA) is used in the chemical industry for manufacturing plastics which are used as food packaging. Data indicate that BPA is released from such products and is widely present in the environment and the human body. So far, the EFSA and the US FDA have determined "safe" BPA oral exposure levels, and a large amount of data indicates that BPA is harmful even at low-doses. Our previously performed analyses concerning BPA exposure demonstrated the impact of this substance on parasympathetic and peptidergic nerve fibers present within the liver. Therefore, this study concerns BPA exposure and sympathetic intrahepatic innervation in reference to several neuropeptides which modulate neuronal responses: cocaine and amphetamine regulated transcript (CART), galanin (GAL), calcitonin gene-regulated peptide (CGRP) and substance P (SP). Materials and methods. Fifteen young swine at 8 weeks of age were used as experimental models of the juvenile human liver. The pigs were divided into 3 groups and received capsules orally with bisphenol at a dose of 0.05 mg/kg b.w./day; a dose of 0.5 mg/kg b.w./day and placebo capsules as a control. After 28 days of oral BPA intake, the animals were euthanized, perfused with 4% paraformaldehyde (PFA), and livers were collected and fixed in PFA. The cryostat sections were subjected to a routine double-labeling immunofluorescence technique. The primary antibodies were directed against dopamine beta hydroxylase (DbH), which is a marker for sympathetic nerves, and one of the investigated neuropeptides: CART, GAL, CGRP and SP, which co-localized the investigated nerves. Immunoreactive nerves were counted in the liver and the percentage presence of each neuronal combination in particular samples of each experimental group were determined and analyzed statistically. Results. The BPA oral intake at low and ten times higher dosage caused an increase of the number of sympathetic nerve fibers within the porcine liver by 48.6% and 63.7%, respectively. Moreover, BPA exposure caused an increased presence of sympathetic nerve fibers in these two experimental groups, which were co-localized with CART and GAL up to 65.9%/173.2% and 147.4%/126.3%, respectively. At the lower BPA doses of 50 μg/kg b.w./day, the percentages of SP+/DbH+ and CGRP+/DbH+ nerve fibers were similar to the control. 114Michael Thoene et al. However at a ten times higher dose, BPA caused an increased number of SP+/ DbH+ and CGRP+/ DbH+ nerve fibers in the liver, up to 46.4% and 73.5% respectively. Conclusions. BPA caused an increase in the number of sympathetic nerve fibers as well as sympathetic nerve fibers which co-localized with neuropeptides in the porcine liver. The increase in CART and GAL were exceptionally high even at low BPA doses. BPA food contamination may dysregulate liver sympathetic innervation, and thereby may change the oxygenated blood supply, alter metabolism and disrupt the activity of hepatic parenchymal cells.

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Section: Discussionmentioning

confidence: 99%

Alterations in porcine intrahepatic sympathetic nerves after bisphenol A administration

Thoene

Godlewski

Rytel

et al. 2018

Folia Histochem Cytobiol.

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“…Indeed, it has been shown that GLP-1 activates phosphoinositide 3-kinase/PKB in rat hepatocytes and stimulates the activity of glycogen synthase a (23). Alternatively, the effect of GLP-1 on the liver could be mediated by binding to the GLP-1 and glucose receptors on nerve terminals in hepatic hilum area (as well as in the fibers extending into the connective tissue and hepatic lobules and ending on liver parenchymal cells in humans) (14). This in turn would initiate a neural signal to the brain and from the brain via efferent fibers to other organs (adipose tissue, muscle, liver itself) involved in a coordinated response to a glucose challenge.…”

Section: E649mentioning

confidence: 95%

“…These signals (glucose, GLP-1, gastric inhibitory polypeptide, PYY, etc.) are sensed by several areas: gut and afferent nerves and vasculature, wall of the portal vein, liver, and other organs in the general circulation (14). It is possible that the putative effects of exenatide or GLP-1 mediated by portal sensors were mitigated by compensatory changes such that portal denervation by comparison had a minimal impact on the overall response to a glycemic load and oral glucose tolerance.…”

Section: E649mentioning

confidence: 99%

Hepatic portal vein denervation impairs oral glucose tolerance but not exenatide’s effect on glycemia

Ionut¹,

Castro²,

Woolcott³

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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The hepatoportal area is an important glucohomeostatic metabolic sensor, sensing hypoglycemia, hyperglycemia, and hormones such as glucagon-like peptide-1 (GLP-1). We have reported previously that activation of hepatoportal sensors by intraportal infusion of glucose and GLP-1 or by subcutaneous administration of GLP-1 receptor activator exenatide and of intraportal glucose improved glycemia independent of corresponding changes in pancreatic hormones. It is not clear whether this effect is mediated via the portal vein (PV) or by direct action on the liver itself. To test whether receptors in the PV mediate exenatide's beneficial effect on glucose tolerance, we performed 1) paired oral glucose tolerance tests (OGTT) with and without exenatide and 2) intravenous glucose tolerance tests before and after PV denervation in canines. Denervation of the portal vein affected oral glucose tolerance; post-denervation (POST-DEN) OGTT glucose and insulin AUC were 50% higher than before denervation (P = 0.01). However, portal denervation did not impair exenatide's effect to improve oral glucose tolerance (exenatide effect: 48 ± 12 mmol·l⁻¹·min before vs. 64 ± 26 mmol·l⁻¹·min after, P = 0.67). There were no changes in insulin sensitivity or secretion during IVGTTs. Portal vein sensing might play a role in controlling oral glucose tolerance during physiological conditions but not in pharmacological activation of GLP-1 receptors by exenatide.

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“…The liver is affected by both the sympathetic and the parasympathetic nerve systems. These nerve systems modulate information regarding hepatic osmolality, glucose concentrations, and lipid concentrations from the brain through the afferent neurons, and the liver receives varieties of signals including blood flow, bile secretion, and metabolism through the efferent neurons [4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Non-Invasive Method to Diagnose the Liver Fibrosis by Using Electrospinography

Hassan¹,

Omar²,

El-Sayed³

2017

J Neurol Neurosci

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The liver is stimulated by both sympathetic and the parasympathetic nerve systems (Autonomic nervous system ANS). These nerves are consequent from the splanchnic and vagal nerves that surround the portal vein and hepatic artery. The afferent signals which responsible for glucose level, osmolality and lipid level is delivered from portal vein to Central nervous system (CNS). In other hand the efferent signals came from CNS to liver by using sympathetic nerves to control in liver functions. The IP injection of carbon tetrachloride CCl 4 make a hepatotoxicity for liver cell and this variation will be detected by afferent nerves to CNS. This will make CNS sent efferent signal different from the normal one. The efferent signals from the surface of spinal cord were recorded by using Electrospinogram device, which measure the potential difference for a specific segment which specify liver innervation (T7-T12). Then these signals were used to diagnose changes in liver functions which result in diagnosis liver diseases in non-invasive method by using only two electrodes on the skin surface of specific segment on spinal cord.

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Hepatic Nervous System and Neurobiology of the Liver

Cited by 143 publications

References 101 publications

Alterations in porcine intrahepatic sympathetic nerves after bisphenol A administration

Alterations in porcine intrahepatic sympathetic nerves after bisphenol A administration

Hepatic portal vein denervation impairs oral glucose tolerance but not exenatide’s effect on glycemia

Non-Invasive Method to Diagnose the Liver Fibrosis by Using Electrospinography

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