Immunohistochemical localization of transient receptor potential vanilloid type 1 and insulin receptor substrate 2 and their co-localization with liver-related neurons in the hypothalamus and brainstem

The central nervous system plays an important role in the regulation of energy balance and glucose homeostasis mainly via controlling the autonomic output to the visceral organs. The autonomic output is regulated by hormones and nutrients to maintain adequate energy and glucose homeostasis. Insulin action is mediated via insulin receptors (IR) resulting in phosphorylation of insulin receptor substrates (IRS) inducing activation of downstream pathways. Furthermore, insulin enhances transient receptor potential vanilloid type 1 (TRPV1) mediated currents. Activation of the TRPV1 receptor increases excitatory neurotransmitter release in autonomic centers of the brain, thereby impacting energy and glucose homeostasis. The aim of this study is to determine co-expression of IRS2 and TRPV1 receptors in the paraventricular nucleus of the hypothalamus (PVN) and dorsal motor nucleus of the vagus (DMV) in the mouse brain as well as expression of IRS2 and TRPV1 receptors at liver-related preautonomic neurons pre-labeled with a trans-neural, viral tracer (PRV-152). The data indicate that IRS2 and TRPV1 receptors are present and co-express in the PVN and the DMV. A large portion (over 50%) of the liver-related preautonomic DMV and PVN neurons expresses IRS2. Moreover, the majority of liver-related DMV and PVN neurons also express TRPV1 receptors, suggesting that insulin and TRPV1 actions may affect liver-related preautonomic neurons.

Research Highlights
► IRS2 and TRPV1 co-expressed in the hypothalamus and brainstem.
► Liver-related preautonomic neurons express IRS2 in the PVN and DMV.
► Liver-related preautonomic neurons express TRPV1 receptors in the PVN and DMV.
► TRPV1 and IRS2 could contribute to central autonomic control of the liver.