Activation of Human Brown Adipose Tissue by a β3-Adrenergic Receptor Agonist

White adipocytes store energy differently than brown and brite adipocytes which dissipate energy under the form of heat. Studies have shown that adipocytes are able to respond to bacteria thanks to the presence of Toll-like receptors at their surface. Despite this, little is known about the involvement of each class of adipocytes in the infectious response. We treated mice for one week with a β3-adrenergic receptor agonist to induce activation of brown adipose tissue and brite adipocytes within white adipose tissue. Mice were then injected intraperitoneally with E. coli to generate acute infection. The metabolic, infectious and inflammatory parameters of the mice were analysed during 48 hours after infection. Our results shown that in response to bacteria, thermogenic activity promoted a discrete and local anti-inflammatory environment in white adipose tissue characterized by the increase of the IL-1RA secretion. More generally, activation of brown and brite adipocytes did not modify the host response to infection including no additive effect with fever and an equivalent bacteria clearance and inflammatory response. In conclusion, these results suggest an IL-1RA-mediated immunomodulatory activity of thermogenic adipocytes in response to acute bacterial infection and open a way to characterize their effect along more chronic infection as septicaemia.

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Changes in β1- and β2-adrenergic receptor mRNA levels in brown adipose tissue and heart of hypothyroid rats

Biochemical Journal ◽

10.1042/bj2770625 ◽

1991 ◽

Vol 277 (3) ◽

pp. 625-629 ◽

Cited By ~ 30

Author(s):

J P Revelli ◽

R Pescini ◽

P Muzzin ◽

J Seydoux ◽

M G Fitzgerald ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Adrenergic Receptor ◽

State Level ◽

Total Density ◽

Mrna Levels ◽

Interscapular Brown Adipose Tissue ◽

Brown Adipose ◽

Displacement Experiments ◽

Beta 2

The aim of the present work was to study the effect of hypothyroidism on the expression of the beta-adrenergic receptor (beta-AR) in interscapular brown adipose tissue and heart. The total density of plasma membrane beta-AR per tissue is decreased by 44% in hypothyroid rat interscapular brown adipose tissue and by 55% in hypothyroid rat heart compared with euthyroid controls. The effects of hypothyroidism on the density of both beta 1- and beta 2-AR subtypes were also determined in competition displacement experiments. The densities of beta 1- and beta 2-AR per tissue are decreased by 50% and 48% respectively in interscapular brown adipose tissue and by 52% and 54% in the heart. Northern blot analysis of poly(A)+ RNA from hypothyroid rat interscapular brown adipose tissue demonstrated that the levels of beta 1- and beta 2-AR mRNA per tissue are decreased by 73% and 58% respectively, whereas in hypothyroid heart, only the beta 1-AR mRNA is decreased, by 43%. The effect of hypothyroidism on the beta 1-AR mRNA is significantly more marked in the interscapular brown adipose tissue than in the heart. These results indicate that beta-AR mRNA levels are differentially regulated in rat interscapular brown adipose tissue and heart, and suggest that the decrease in beta-AR number in interscapular brown adipose tissue and heart of hypothyroid animals may in part be explained by a decreased steady-state level of beta-AR mRNA.

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The role of the brown adipose tissue in β3-adrenergic receptor activation-induced sleep, metabolic and feeding responses

Scientific Reports ◽

10.1038/s41598-017-01047-1 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 15

Author(s):

Éva Szentirmai ◽

Levente Kapás

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Adrenergic Receptor ◽

Receptor Activation ◽

Brown Adipose

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00039.2010 ◽

2010 ◽

Vol 299 (1) ◽

pp. R277-R290 ◽

Cited By ~ 51

Author(s):

Wei-Hua Cao ◽

Christopher J. Madden ◽

Shaun F. Morrison

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Receptor Agonist ◽

Nucleus Tractus Solitarius ◽

Ventrolateral Medulla ◽

Prostaglandin E ◽

Experimental Conditions ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis ◽

Raphe Pallidus

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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Central efferent pathways mediating skin cooling-evoked sympathetic thermogenesis in brown adipose tissue

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00427.2006 ◽

2007 ◽

Vol 292 (1) ◽

pp. R127-R136 ◽

Cited By ~ 139

Author(s):

Kazuhiro Nakamura ◽

Shaun F. Morrison

Keyword(s):

Heart Rate ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Receptor Agonist ◽

Excitatory Amino Acid ◽

Defense Responses ◽

Hypothalamic Nucleus ◽

Brown Adipose ◽

Skin Cooling ◽

Efferent Pathways

Control of thermoregulatory effectors by the autonomic nervous system is a critical component of rapid cold-defense responses, which are triggered by thermal information from the skin. However, the central autonomic mechanism driving thermoregulatory effector responses to skin thermal signals remains to be determined. Here, we examined the involvement of several autonomic brain regions in sympathetic thermogenic responses in brown adipose tissue (BAT) to skin cooling in urethane-chloralose-anesthetized rats by monitoring thermogenic [BAT sympathetic nerve activity (SNA) and BAT temperature], metabolic (expired CO2), and cardiovascular (arterial pressure and heart rate) parameters. Acute skin cooling, which did not reduce either rectal (core) or brain temperature, evoked increases in BAT SNA, BAT temperature, expired CO2, and heart rate. Skin cooling-evoked thermogenic, metabolic, and heart rate responses were inhibited by bilateral microinjections of bicuculline (GABAA receptor antagonist) into the preoptic area (POA), by bilateral microinjections of muscimol (GABAA receptor agonist) into the dorsomedial hypothalamic nucleus (DMH), or by microinjection of muscimol, glycine, 8-OH-DPAT (5-HT1A receptor agonist), or kynurenate (nonselective antagonist for ionotropic excitatory amino acid receptors) into the rostral raphe pallidus nucleus (rRPa) but not by bilateral muscimol injections into the lateral/dorsolateral part or ventrolateral part of the caudal periaqueductal gray. These results implicate the POA, DMH, and rRPa in the central efferent pathways for thermogenic, metabolic, and cardiac responses to skin cooling, and suggest that these pathways can be modulated by serotonergic inputs to the medullary raphe.

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