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Liver-brain's Neural Circuitry

Introduction of Hepatic Nervous System

The liver is an organ mainly for metabolic function in humans. The hepatic nervous system consists of both afferent neurons and efferent neurons. Among them, the afferent neurons are involved in the perception of glucose, lipids, and metabolites. The efferent neurons are important for the modulation of fibrosis, regulation of metabolic, and function of biliary. In this case, the liver can simultaneously act as a sensor and an effector affected by nerve signals and ablation.

As a part of the peripheral nervous system, the autonomic nervous system plays an important role in the regulation of multiple physiological events in the liver. In addition, the autonomic nervous system can be further divided into the sympathetic and parasympathetic nerves which can transmit signals in the brain/liver nerve axis.

Gross anatomy of the hepatic nervous system. Fig.1 Gross anatomy of the hepatic nervous system. (Jensen, 2013)

Hepatic Afferent Nerves

The liver is always regulated by afferent and efferent autonomic nerves and differs between different species. The liver has been served as a promising sensor to detect the level of glucose and fatty acid. After food digestion, macronutrients reach the liver, where chemoreceptors can sense ions and nutrients, and then send signals to the brain. By tracking neural activity in animal models, mechanical information about the liver afferent system can be obtained. The information would be helpful for the development of therapies against obesity and diabetes.

In mammals, the osmotic pressure of extracellular fluid (ECF) is regulated by the osmosensing system in different organ systems. The liver can effectively sense changes in blood osmotic pressure. Compared with other organs, the liver contains receptors for monitoring the homeostasis of body fluids and thus has obvious advantages in detecting ions. Therefore, the liver is the most ideal organ for whole-body blood ion concentration detection.

Metabolic Sensing of the Liver

It is well-known that glucose sensing occurs in different cell types of the brain. Some studies have also shown glucose sensing by the liver, and GLUT2 acts as a portal glucose sensor and plays a role in the detection of hyperglycemia. Unlike the brain, the liver cannot detect the rapid onset of hypoglycemia. As for lipid sensing in the liver, a possible pathway relates to the activation of protein kinase C (PKC) δ, θ, and ε.

Sensation of Ions by hepatic afferent nerves. Fig.2 Sensation of Ions by hepatic afferent nerves. (Jensen, 2013)

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  1. Jensen, K.; et al. Hepatic nervous system and neurobiology of the liver. Comprehensive Physiology. 2013, 3(2): 655.

For Research Use Only. Not For Clinical Use.