Inhibition of brown adipose tissue thermogenesis by neurons in the ventrolateral medulla and in the nucleus tractus solitarius

Neurons in the ventrolateral medulla (VLM) and in the nucleus tractus solitarius (NTS) play important roles in the regulation of cardiovascular and other autonomic functions. In the present study, we demonstrate an inhibition of brown adipose tissue (BAT) thermogenesis evoked by activation of neurons in the VLM, as well as by neurons in the intermediate NTS, of chloralose/urethane-anesthetized, artificially ventilated rats. Activation of neurons in either rostral VLM or caudal VLM with N-methyl-d-aspartate (12 nmol) reversed the cold-evoked increase in BAT sympathetic nerve activity (SNA), BAT temperature, and end-expired CO2. Disinhibition of neurons in either VLM or NTS with the GABAA receptor antagonist, bicuculline (30 pmol), reversed the increases in BAT SNA, BAT temperature, and end-expired CO2 that were elicited 1) by cold defense; 2) during the febrile model of nanoinjection of prostaglandin E2 into the medial preoptic area; 3) by activation of neurons in the dorsomedial hypothalamus or in the rostral raphe pallidus (rRPa); or 4) by the μ-opioid receptor agonist fentanyl. Combined, but not separate, inhibitions of neurons in the VLM and in the NTS, with the GABAA receptor agonist, muscimol (120 pmol/site), produced increases in BAT SNA, BAT temperature, and expired CO2, which were reversed by nanoinjection of glycine (30 nmol) into the rRPa. These findings suggest that VLM and NTS contain neurons whose activation inhibits BAT thermogenesis, that these neurons receive GABAergic inputs that are active under these experimental conditions, and that neurons in both sites contribute to the tonic inhibition of sympathetic premotor neuronal activity in the rRPa that maintains a low level of BAT thermogenesis in normothermic conditions.

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Brown adipose tissue thermogenesis contributes to fentanyl-evoked hyperthermia

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00669.2004 ◽

2005 ◽

Vol 288 (3) ◽

pp. R723-R732 ◽

Cited By ~ 22

Author(s):

Wei-Hua Cao ◽

Shaun F. Morrison

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Opioid Receptors ◽

Receptor Activation ◽

Opioid Antagonist ◽

Ventrolateral Medulla ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis ◽

Raphe Pallidus ◽

Μ Opioid Receptors

μ-Opioid receptor activation increases body temperature and affects cardiovascular function. In the present study, fentanyl was administered intravenously [100 μg/kg (300 nmol/kg) iv] and intracerebroventricularly [3.4 μg (10 nmol) in 10 μl icv] in urethane-chloralose-anesthetized, artificially ventilated rats. Increases in brown adipose tissue (BAT) sympathetic nerve activity (SNA) (peak, +326% of control), BAT temperature (peak, +0.8°C), renal SNA (peak, +146% of control), and heart rate (HR; peak, +32 beats/min) produced by intravenous fentanyl were abolished by premamillary transection of the neuraxis but were mimicked by intracerebroventricular administration of fentanyl, which also increased arterial pressure (AP; peak, +12 mmHg). Pretreatment with the opioid antagonist naloxone (100 nmol in 10 μl icv) eliminated the intracerebroventricular fentanyl-evoked responses. Microinjection of glycine (0.5 M, 60 nl) to inhibit local neurons in the rostral raphe pallidus (RPa) selectively reversed the intracerebroventricular fentanyl-evoked increases in BAT SNA and HR, while the fentanyl-evoked excitation in RSNA, the pressor responses, and the tachycardic responses were reversed by inhibition of neurons in the rostral ventrolateral medulla (RVLM). Prior inhibition of neurons in the dorsomedial hypothalamus eliminated the intracerebroventricular fentanyl-evoked increases in BAT SNA, BAT temperature, and HR, but not those in RSNA or AP. These results indicate that activation of central μ-opioid receptors with fentanyl can elicit BAT thermogenesis and cardiovascular stimulation through excitation of the sympathetic outflows to BAT, kidney, and heart. Activation of neurons in the rostral RPa and RVLM are essential for the increases in BAT thermogenesis and renal sympathoexcitation, respectively, induced by activation of central μ-opioid receptors. BAT thermogenesis could contribute to fentanyl-evoked hyperthermia, particularly in infants where BAT plays a significant role in thermoregulation.

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Dopaminergic Input from the Posterior Hypothalamus to the Raphe Pallidus Area Inhibits Brown Adipose Tissue Thermogenesis

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00149.2021 ◽

2021 ◽

Author(s):

Ellen Paula Santos da Conceição Furber ◽

Clarissa M.D. Mota ◽

Edward Veytsman ◽

Shaun F. Morrison ◽

Christopher J. Madden

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Posterior Hypothalamus ◽

Brown Adipose ◽

Premotor Neurons ◽

Brown Adipose Tissue Thermogenesis ◽

Pre Treatment ◽

Type 3 ◽

Raphe Pallidus

Systemic administration of dopamine (DA) receptor agonists leads to falls in body temperature. However, the central thermoregulatory pathways modulated by DA have not been fully elucidated. Here we identified a source and site of action contributing to DA's hypothermic action by inhibition of brown adipose tissue (BAT) thermogenesis. Nanoinjection of the type 2 and type 3 DA receptor (D2R/D3R) agonist, 7-OH-DPAT, in the rostral raphe pallidus area (rRPa) inhibits the sympathetic activation of BAT evoked by cold exposure or by direct activation of NMDA receptors in the rRPa. Blockade of D2R/D3R in the rRPa with nanoinjection of SB-277011A increases BAT thermogenesis, consistent with a tonic release of DA in the rRPa contributing to inhibition of BAT thermogenesis. Accordingly, D2R are expressed in cold-activated and serotonergic neurons in the rRPa and anatomical tracing studies revealed that neurons in the posterior hypothalamus (PH) are a source of dopaminergic input to the rRPa. Disinhibitory activation of PH neurons with nanoinjection of gabazine inhibits BAT thermogenesis, which is reduced by pre-treatment of the rRPa with SB-277011A. In conclusion, the rRPa, the site of sympathetic premotor neurons for BAT, receives a tonically-active, dopaminergic input from the PH that suppresses BAT thermogenesis.

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Glutamate receptors in the raphe pallidus mediate brown adipose tissue thermogenesis evoked by activation of dorsomedial hypothalamic neurons

Neuropharmacology ◽

10.1016/j.neuropharm.2006.03.031 ◽

2006 ◽

Vol 51 (3) ◽

pp. 426-437 ◽

Cited By ~ 67

Author(s):

Wei-Hua Cao ◽

Shaun F. Morrison

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Glutamate Receptors ◽

Hypothalamic Neurons ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis ◽

Raphe Pallidus

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An Orexinergic Projection from Perifornical Hypothalamus to Raphe Pallidus Increases Rat Brown Adipose Tissue Thermogenesis

Journal of Neuroscience ◽

10.1523/jneurosci.3909-11.2011 ◽

2011 ◽

Vol 31 (44) ◽

pp. 15944-15955 ◽

Cited By ~ 135

Author(s):

D. Tupone ◽

C. J. Madden ◽

G. Cano ◽

S. F. Morrison

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis ◽

Raphe Pallidus

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Corticotropin releasing factor increases in brown adipose tissue thermogenesis and heart rate through dorsomedial hypothalamus and medullary raphe pallidus

Neuroscience ◽

10.1016/j.neuroscience.2006.02.027 ◽

2006 ◽

Vol 140 (2) ◽

pp. 711-721 ◽

Cited By ~ 32

Author(s):

M. Cerri ◽

S.F. Morrison

Keyword(s):

Heart Rate ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Corticotropin Releasing Factor ◽

Dorsomedial Hypothalamus ◽

Brown Adipose ◽

Medullary Raphe ◽

Brown Adipose Tissue Thermogenesis ◽

Raphe Pallidus

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Glucoprivation in the ventrolateral medulla decreases brown adipose tissue sympathetic nerve activity by decreasing the activity of neurons in raphé pallidus

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00449.2011 ◽

2012 ◽

Vol 302 (2) ◽

pp. R224-R232 ◽

Cited By ~ 24

Author(s):

C. J. Madden

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Cold Exposure ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Ventrolateral Medulla ◽

Nerve Activity ◽

Hypothalamic Area ◽

Brown Adipose ◽

Raphe Pallidus

In urethane/α-chloralose anesthetized rats, cold exposure increased brown adipose tissue sympathetic nerve activity (BAT SNA: +699 ± 104% control). Intravenous administration of 2-deoxy-d-glucose (2-DG; 200 mg·ml−1·kg−1) reversed the cold-evoked activation of BAT SNA (nadir: 139 ± 36% of control) and decreased BAT temperature (−1.1 ± 0.2°C), expired CO2 (−0.4 ± 0.1%), and core temperature (−0.5 ± 0.0). Similarly, unilateral nanoinjection of the glucoprivic agent 5-thioglucose (5-TG; 12 μg/100 nl) in the ventrolateral medulla (VLM) completely reversed the cold-evoked increase in BAT SNA (nadir: 104 ± 7% of control), and decreased TBAT (−1.4 ± 0.3°C), expired CO2 (−0.2 ± 0.0%), and heart rate (−35 ± 10 beats/min). The percentage of rostral raphé pallidus (RPa)-projecting neurons in the dorsal hypothalamic area/dorsomedial hypothalamus that expressed Fos in response to cold exposure (ambient temperature: 4–10°C) did not differ between saline (28 ± 6%) and 2-DG (30 ± 5%) pretreated rats, whereas the percentage of spinally projecting neurons in the RPa/raphé magnus that expressed Fos in response to cold exposure was lower in 2-DG- compared with saline-pretreated rats (22 ± 6% vs. 42 ± 5%, respectively). The increases in BAT SNA evoked by nanoinjection of bicuculline in the RPa or by transection of the neuraxis at the pontomedullary border were resistant to inhibition by glucoprivation. These results suggest that neurons within the VLM play a role in the glucoprivic inhibition of BAT SNA and metabolism, that this inhibition requires neural structures rostral to the pontomedullary border, and that this inhibition is mediated by a GABAergic input to the RPa.

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