Pathophysiological Mechanisms That Alter the Autonomic Brain-Liver Communication in Metabolic Diseases

Abstract

The brain influences liver metabolism through many neuroendocrine and autonomic mechanisms that have evolved to protect the organism against starvation and hypoglycemia. Unfortunately, what is normally an effective way to prevent death has become dysregulated in modern obesogenic environments, but the pathophysiological mechanisms behind metabolic dyshomeostasis are still unclear. In this Mini-Review, we provide our thoughts regarding obesity and type 2 diabetes as diseases of the autonomic nervous system. We discuss the pathophysiological mechanisms that alter the autonomic brain-liver communication in these diseases, and how they could represent important targets to prevent or treat metabolic dysfunctions. We discuss how sympathetic hyperactivity to the liver may represent an early event in the progression of metabolic diseases and could progressively lead to hepatic neuropathy. We hope that this discussion will inspire and help framing a model on the importance of better understanding the chronology of autonomic dysfunctions in the liver in order to apply the right strategy at the right time.

Hepatic Innervations and Nonalcoholic Fatty Liver Disease

“…These structural alterations likely come along with impaired nerve functionality and lack of adequate signaling, which further affect the receptors, as a vicious cycle of hepatic noradrenergic pathology. All these may contribute to a multiphase hepatic "catecholamine resistance" (inability of (nor)adrenaline to induce a defined response), 150 which should be considered when planning and evaluating pharmacological studies or pharmacotherapeutic strategies targeting the SNS in NAFLD.…”