The role of the autonomic nervous liver innervation in the control of energy metabolism

Abstract

Despite a longstanding research interest ever since the early work by Claude Bernard, the functional significance of autonomic liver innervation, either sympathetic or parasympathetic, is still ill defined. This scarcity of information not only holds for the brain control of hepatic metabolism, but also for the metabolic sensing function of the liver and the way in which this metabolic information from the liver affects the brain. Clinical information from the bedside suggests that successful human liver transplantation (implying a complete autonomic liver denervation) causes no life threatening metabolic derangements, at least in the absence of severe metabolic challenges such as hypoglycemia. However, from the benchside, data are accumulating that interference with the neuronal brain-liver connection does cause pronounced changes in liver metabolism. This review provides an extensive overview on how metabolic information is sensed by the liver, and how this information is processed via neuronal pathways to the brain. With this information the brain controls liver metabolism and that of other organs and tissues. We will pay special attention to the hypothalamic pathways involved in these liver-brain-liver circuits. At this stage, we still do not know the final destination and processing of the metabolic information that is transferred from the liver to the brain. On the other hand, in recent years, there has been a considerable increase in the understanding which brain areas are involved in the control of liver metabolism via its autonomic innervation. However, in view of the ever rising prevalence of type 2 diabetes, this potentially highly relevant knowledge is still by far too limited. Thus the autonomic innervation of the liver and its role in the control of metabolism needs our continued and devoted attention.

Galantamine Attenuates Type 1 Diabetes and Inhibits Anti-Insulin Antibodies in Nonobese Diabetic Mice

“…A role for the vagus nerve has also been shown in suppressing pancreatic inflammation; surgical transection of the vagus nerve (vagotomy) results in exacerbated murine pancreatitis, thus indicating a tonic antiinflammatory role of these innervations (63). The vagus nerve also innervates the liver, and it is known that vagus nerve-mediated signaling suppresses hepatic glucose production (64)(65)(66), one of the main determinants of fasting blood glucose levels. We suggest that galantamine-mediated activation of the vagus nerve reduces pancreatic inflammation and delays onset of diabetes.…”

Negative feedforward control of body fluid homeostasis by hepatorenal reflex

“…However, it should be noted that hepaticdenervated animals lose not only the afferent nerves involved in the Na + -sensitive mechanism, but also other afferent nerves, that is those for the baro-, glucose-, amino acid-, and metabolite-sensitive mechanisms and the efferent innervation of the liver. Therefore, hepatic denervation also influences hepatic hemodynamics through changes in the vascular tone of the hepatic artery and portal vein, in the metabolism and in biliary function [45][46][47][48] . Therefore, more-selective hepatic denervation or another experimental method that preserves the other hepatic innervation is required.…”

Control of metabolism by nutrient-regulated nuclear receptors acting in the brain

“…The PVN links the energy balance regulatory system to the ANS [124,146]. More precisely, the PVN is the [148] and the liver [149] has been demonstrated, indicating that the ANS directly transfers circadian information to its cellular targets in peripheral organs [150].…”