Stimulation of the hypothalamic arcuate nucleus increases brown adipose tissue nerve activity via hypothalamic paraventricular and dorsomedial nuclei

Abstract

Hypothalamic arcuate nucleus (ARCN) stimulation elicited increases in sympathetic nerve activity (IBATSNA) and temperature (TBAT) of interscapular brown adipose tissue (IBAT). The role of hypothalamic dorsomedial (DMN) and paraventricular (PVN) nuclei in mediating these responses was studied in urethane-anesthetized, artificially ventilated, male Wistar rats. In different groups of rats, inhibition of neurons in the DMN and PVN by microinjections of muscimol attenuated the increases in IBATSNA and TBAT elicited by microinjections of N-methyl-d-aspartic acid into the ipsilateral ARCN. In other groups of rats, blockade of ionotropic glutamate receptors by combined microinjections of D(-)-2-amino-7-phosphono-heptanoic acid (D-AP7) and NBQX into the DMN and PVN attenuated increases in IBATSNA and TBAT elicited by ARCN stimulation. Blockade of melanocortin 3/4 receptors in the DMN and PVN in other groups of rats resulted in attenuation of increases in IBATSNA and TBAT elicited by ipsilateral ARCN stimulation. Microinjections of Fluoro-Gold into the DMN resulted in retrograde labeling of cells in the ipsilateral ARCN, and some of these cells contained proopiomelanocortin (POMC), α-melanocyte-stimulating hormone (α-MSH), or vesicular glutamate transporter-3. Since similar projections from ARCN to the PVN have been reported by us and others, these results indicate that neurons containing POMC, α-MSH, and glutamate project from the ARCN to the DMN and PVN. Stimulation of ARCN results in the release of α-MSH and glutamate in the DMN and PVN which, in turn, cause increases in IBATSNA and TBAT.

Voluntary Corn Oil Ingestion Increases Energy Expenditure and Interscapular UCP1 Expression Through the Sympathetic Nerve in C57BL/6 Mice

“…Chitravanshi et al. more directly observed that arcuate nucleus stimulation elicited increases in sympathetic nerve activity and stimulated thermogenesis in IBAT . We also observed that small amounts of fat emulsion (intralipid) applied to the tongue stimulated sympathetic nerve activity innervated to IBAT in urethane anesthetized rats (unpublished data).…”

Food Perception Primes Hepatic ER Homeostasis via Melanocortin-Dependent Control of mTOR Activation

“…Thereby, they can adapt numerous processes in the integrated regulation of whole-body metabolism, including control of hepatic glucose metabolism and VLDL secretion, BAT activation, and adipose tissue lipolysis, (Balthasar et al, 2004; Berglund et al, 2012; Kőnner et al, 2007; Parton et al, 2007; Ruud et al, 2017; Scherer et al, 2011, 2016; Shin et al, 2017; Steculorum et al, 2016). Importantly, POMC neurons have been demonstrated to promote sympathetic nerve activation in response to leptin and insulin (i.e., in control of SNA in various tissues) (Bell et al, 2018; Chhabra et al, 2017; Chitravanshi et al, 2016; Rahmouni et al, 2003). Although our experiments clearly reveal that chemogenetic POMC neuron activation is sufficient to rapidly induce hepatic SNA and that optogenetic POMC neuron activation promotes S6 phosphorylation and Xbp1 splicing, they do not rule out the possibility that the concomitant inhibition of AgRP neuron activity may also contribute to these effects upon sensory food perception.…”

Control of Energy Expenditure by AgRP Neurons of the Arcuate Nucleus: Neurocircuitry, Signaling Pathways, and Angiotensin

“…However, selective restoration of MC 4 R expression in the PVN of MC 4 R -null mice failed to normalize resting oxygen consumption [37], and chemogenetic activation of MC 4 R neurons in the PVN had no effect on oxygen consumption [38]. On the other hand, MC 3 R/MC 4 R blockade in the PVN was recently reported to blunt the increase in BAT SNA and BAT temperature in adult male Wistar rats microinjected with N-methyl-D-aspartate (NMDA) in the ARC [39]. In this report, energy expenditure was not measured.…”

“…Chitravanshi et al [39] injected FluoroGold into the DMH and observed retrograde labeling of ARC neurons. Neuronal labeling demonstrated that 30 to 40% of all POMC-positive neurons, α-MSH-positive neurons and Vglut3-positive neurons contained FluoroGold.…”