Author: Lucas Silva
Review Article
Vagal Nerve in Metabolic Homeostasis and Neuroendocrine Control of Hepatic Gene Expression
Lucas Silva*
Department of Molecular Biology, University of São Paulo, São Paulo, Brazil
Published: 15 October 2021
Abstract
Adiponectin, a multifunctional adipokine predominantly secreted by adipocytes, has garnered substantial attention for its insulin-sensitizing, anti-inflammatory, and cardioprotective roles in metabolic regulation. Low circulating adiponectin levels are consistently associated with obesity, insulin resistance, type 2 diabetes, and Non-Alcoholic Fatty Liver Disease (NAFLD). Despite its physiological importance, the regulatory mechanisms governing adiponectin secretion remain incompletely understood. Recent studies have begun to elucidate the role of the autonomic nervous system, particularly the vagus nerve, in modulating systemic metabolic signals through its extensive innervation of visceral organs, including the liver. This review synthesizes emerging data that implicate the vagus nerve as a critical mediator of adiponectin regulation, focusing on its interactions with hepatic gene expression. The vagus nerve, comprising both afferent (sensory) and efferent (motor) fibers, facilitates a dynamic bidirectional communication axis between the brain and peripheral tissues. Evidence from murine models suggests that vagal efferent stimulation can upregulate hepatic expression of genes associated with adiponectin secretion and systemic availability. Conversely, vagotomy or pharmacological blockade of vagal signaling results in significant reductions in serum adiponectin, underscoring the importance of this neural-liver axis.
Hepatic gene expression profiles reveal that specific transcription factors and signaling molecules are modulated in response to vagal stimulation. These include key regulators of lipid metabolism and adipokine biosynthesis, such as peroxisome Proliferator-Activated Receptors (PPARs), AMP-Activated Protein Kinase (AMPK), and Fibroblast Growth Factor 21 (FGF21). The interplay between these factors influences not only local liver metabolism but also systemic energy homeostasis, with downstream effects on insulin sensitivity and inflammation. Understanding the intricate relationship between vagal nerve signaling and hepatic control of adiponectin production opens promising avenues for therapeutic strategies aimed at restoring adipokine balance in metabolic disorders. Modulating vagal tone through neuromodulation techniques, pharmacological agents, or lifestyle interventions such as Vagus Nerve Stimulation (VNS), dietary manipulation, and exercise may serve as potential tools to enhance adiponectin levels. This review provides a comprehensive overview of current findings on vagus nerve-mediated hepatic regulation of adiponectin and its implications for metabolic disease management, advocating for further exploration of this neuro-metabolic interface in translational research.
Keywords: Adiponectin signaling; Vagus nerve stimulation; Hepatic gene regulation; Neuro-metabolic axis; Insulin sensitivity; Autonomic nervous system; Metabolic homeostasis
