Neuropeptide Y Inputs to Neurons in the Dorsomedial Hypothalamus Tonically Inhibit Brown Adipose Tissue (BAT) Sympathetic Nerve Activity (SNA) via NPY Y1 Receptors

Abstract

Hypothalamic Neuropeptide Y (NPY) has been implicated in metabolic homeostasis. For example, NPY acts in the paraventricular nucleus of the hypothalamus to decrease BAT SNA. NPY neurons within the dorsomedial hypothalamus (DMH) have also been implicated in energy balance, however the role of NPY inputs to BAT regulatory neurons in the DMH has not been assessed. The present study tested the hypothesis that neurons in the DMH receive a NPY‐containing input that contributes to the regulation of BAT SNA via activation of NPY Y1 receptors. First, administration of a retrograde tracer (cholera toxin B) into the raphe pallidus area (RPa) and immunohistochemistry for NPY demonstrated that CtB‐labeled (RPa‐projecting) DMH neurons receive close appositions from NPY‐positive fibers. In addition, bilateral nanoninjections of the NPY Y1 receptor antagonist BIBO3304 (2mM, 60nl) into the DMH increased BAT SNA +424±110% baseline, TBAT (+2.2±0.5 °C) and expired CO2 (+1.2±0.1%). In conclusion, NPY inputs to neurons in the DMH tonically inhibit BAT SNA and BAT thermogenesis via activation of NPY Y1 receptors.Support or Funding InformationNIH DK112198