Medullary Reticular Neurons Mediate Neuropeptide Y-Induced Metabolic Inhibition and Mastication

• Published in: Cell metabolism Vol. 25; no. 2; pp. 322 - 334
• Main Authors: Nakamura, Yoshiko, Yanagawa, Yuchio, Morrison, Shaun F., Nakamura, Kazuhiro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.02.2017
• Subjects: Adipose Tissue, Brown - innervation; Adipose Tissue, Brown - metabolism; Animals; brown adipose tissue; cardiovascular; feeding; Feeding Behavior; GABAergic Neurons - metabolism; hunger; Hypothalamus - metabolism; Male; Mastication; medulla; Medulla Oblongata - metabolism; metabolism; Motor Neurons - metabolism; Myocardium - metabolism; Myocardium - pathology; neural circuit; Neurons - metabolism; Neuropeptide Y - metabolism; obesity; Raphe Nuclei - metabolism; Rats, Sprague-Dawley; Signal Transduction; sympathetic; Sympathetic Nervous System - metabolism; Synapses - metabolism; Tachycardia - metabolism; Tachycardia - pathology; Thermogenesis; thermoregulation; medulla; neural circuit; brown adipose tissue; sympathetic; feeding; metabolism; cardiovascular; thermoregulation; obesity; hunger
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2016.12.002

Hypothalamic neuropeptide Y (NPY) elicits hunger responses to increase the chances of surviving starvation: an inhibition of metabolism and an increase in feeding. Here we elucidate a key central circuit mechanism through which hypothalamic NPY signals drive these hunger responses. GABAergic neurons in the intermediate and parvicellular reticular nuclei (IRt/PCRt) of the medulla oblongata, which are activated by NPY-triggered neural signaling from the hypothalamus, potentially through the nucleus tractus solitarius, mediate the NPY-induced inhibition of metabolic thermogenesis in brown adipose tissue (BAT) via their innervation of BAT sympathetic premotor neurons. Intriguingly, the GABAergic IRt/PCRt neurons innervating the BAT sympathetic premotor region also innervate the masticatory motor region, and stimulation of the IRt/PCRt elicits mastication and increases feeding as well as inhibits BAT thermogenesis. These results indicate that GABAergic IRt/PCRt neurons mediate hypothalamus-derived hunger signaling by coordinating both autonomic and feeding motor systems to reduce energy expenditure and to promote feeding. [Display omitted] •GABAergic IRt/PCRt neurons innervate sympathetic premotor neurons controlling BAT•Selective activation of GABAergic IRt/PCRt neurons inhibits BAT thermogenesis•Hypothalamic NPY inhibits BAT thermogenesis by activating GABAergic IRt/PCRt neurons•GABAergic IRt/PCRt neurons can also mediate hunger-driven mastication and feeding Hypothalamic neuropeptide Y (NPY) plays a key role in eliciting hunger responses to reduce energy expenditure and increase food intake. Nakamura et al. reveal how GABAergic medullary reticular neurons coordinate both autonomic and feeding motor systems in response to hypothalamic NPY-driven signaling to inhibit brown adipose tissue thermogenesis and stimulate mastication and feeding.