Activation of ChAT+ neuron in dorsal motor vagus (DMV) increases blood glucose through the regulation of hepatic gene expression in mice

[Display omitted] •ChAT+ PNS innervates the liver.•Activation of ChAT+ neurons in DMV brain region increases hepatic ChAT expression.•Increased hepatic ChAT expression results in increased gene expression involving gluconeogenesis and lipogenesis in the liver.•Activation of ChAT+ neurons in DMV brain region increases blood glucose. The brain and peripheral organs communicate through hormones and neural connections. Proper communication is required to maintain normal whole-body energy homeostasis. In addition to endocrine system, from the perspective of neural connections for metabolic homeostasis, the role of the sympathetic nervous system has been extensively studied, but understanding of the parasympathetic nervous system is limited. The liver plays a central role in glucose and lipid metabolism. This study aimed to clarify the innervation of parasympathetic nervous system in the liver and its functional roles in metabolic homeostasis. The liver-specific parasympathetic nervous system innervation (PNS) was shown by tissue clearing, immunofluorescence and transgenic mice at the three-dimensional histological level. The parasympathetic efferent signals were manipulated using a chemogenetic technique and the activation of ChAT+ parasympathetic neurons in dorsal motor vagus (DMV) results in the increased blood glucose through the elevated hepatic gluconeogenic and lipogenic gene expression in the liver. Thus, our study showed the evidence of ChAT+ parasympathetic neurons in the liver and its role for hepatic parasympathetic nervous signaling in glucose homeostasis through the regulation of hepatic gene expression.