Brs3 neurons in the mouse dorsomedial hypothalamus regulate body temperature, energy expenditure, and heart rate, but not food intake

Abstract

Bombesin-like receptor 3 (BRS3) is an orphan G protein-coupled receptor that regulates energy homeostasis and heart rate. We report that acute activation of Brs3 -expressing neurons in the dorsomedial hypothalamus (DMH Brs3 ) increased body temperature (Tb), brown adipose tissue temperature, energy expenditure, heart rate and blood pressure, with no effect on food intake or physical activity. Conversely, activation of Brs3 neurons in the paraventricular nucleus of the hypothalamus (PVH Brs3 ) had no effect on Tb or energy expenditure, but suppressed food intake. Inhibition of DMH Brs3 neurons decreased Tb and energy expenditure, suggesting a necessary role in Tb regulation. We found that the preoptic area provides major input (excitatory and inhibitory) to DMH Brs3 neurons. Optogenetic stimulation of DMH Brs3 projections to the raphe pallidus (RPa) increased Tb. Thus, DMH Brs3 →RPa neurons regulate Tb, energy expenditure and heart rate, and PVH Brs3 neurons regulate food intake. Brs3 expression is a useful marker for delineating energy metabolism regulatory circuitry.

Type I Interferon Limits Viral Dissemination-Driven Clinical Heterogeneity in a Native Murine Betacoronavirus Model of COVID-19

“…Given the high infectivity of MHV amongst mouse colonies, it was not possible in our animal facilities to perform continuous invasive telemetric monitoring of blood pressure and heart rate to better assess heart rate variability or blood pressure. Maintenance of heart rate is in-part controlled by central nervous system (CNS), and especially the hypothalamus and brainstem (Farmer et al, 2016;Pinol et al, 2018). We thus assessed MHV-A59 burden in different parts of the brain and observed profound increases in viral load in the brain, including the hypothalamus and brainstem in IFNAR1-deficient mice relative to wildtype controls ( Figure 4D, Supplemental Figure S4E).…”

Discrete TrkB-expressing neurons of the dorsomedial hypothalamus regulate feeding and thermogenesis

“…Thermogenic activity in BAT drives both increased body temperature and energy expenditure as well as the utilization of fat, which results in a lower RER, thus, it is likely that DMH TrkB neurons promote negative energy balance by regulating BAT activity. Many previous studies implicate DMH neuronal activity in promoting thermogenesis through an increase in sympathetic nerve activity (SNA) that also affects heart rate and blood pressure (12,20,21). Intriguingly, we found that stimulation of DMH TrkB neurons in mice did not alter heart rate ( Figure 2J) or mean arterial pressure ( Figure 2K).…”

“…The DMH is centrally positioned in an established thermoregulatory neurocircuit, receiving inputs from the preoptic area (POA) (8,14,15) and sending excitatory projections to pre-autonomic neurons in the raphe pallidus (RPa) (12,(16)(17)(18) that promote sympathetic activity in BAT leading to increased thermogenesis. Direct chemical stimulation of the DMH (19), or activation of select populations of thermogenic DMH neurons (8,12,17,20) leads to increased body temperature and energy expenditure, but also significantly increases heart rate and blood pressure (12,18,20,21). An inability to target increased sympathetic tone specifically in BAT without affecting other target tissues has greatly hampered strategies to treat obesity by targeting thermogenesis (5,6).…”

Cool(ing) brain stem GABA neurons

“…[4][5][6][7][8] Some POA populations regulate BAT via descending GABAergic projections to the DMH, but BATregulating DMH neurons also receive glutamatergic input from the POA. [4][5][6]9 The DMH then uses descending projections to the RPa to regulate BAT activity. [8][9][10] Just as DRN Vgat neurons are a new addition to the list of contributors to the neural control of BAT, it is likely that other novel neuronal populations will be identified.…”

“…[4][5][6]9 The DMH then uses descending projections to the RPa to regulate BAT activity. [8][9][10] Just as DRN Vgat neurons are a new addition to the list of contributors to the neural control of BAT, it is likely that other novel neuronal populations will be identified.…”