scholarly journals Hypothalamic Regulation of Brown Adipose Tissue Thermogenesis and Energy Homeostasis

2015 ◽  
Vol 6 ◽  
Author(s):  
Wei Zhang ◽  
Sheng Bi
2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ellen Paula Santos da Conceição ◽  
Shaun F. Morrison ◽  
Georgina Cano ◽  
Pierfrancesco Chiavetta ◽  
Domenico Tupone

Abstract Within the central neural circuitry for thermoregulation, the balance between excitatory and inhibitory inputs to the dorsomedial hypothalamus (DMH) determines the level of activation of brown adipose tissue (BAT) thermogenesis. We employed neuroanatomical and in vivo electrophysiological techniques to identify a source of excitation to thermogenesis-promoting neurons in the DMH that is required for cold defense and fever. Inhibition of median preoptic area (MnPO) neurons blocked the BAT thermogenic responses during both PGE2-induced fever and cold exposure. Disinhibition or direct activation of MnPO neurons induced a BAT thermogenic response in warm rats. Blockade of ionotropic glutamate receptors in the DMH, or brain transection rostral to DMH, blocked cold-evoked or NMDA in MnPO-evoked BAT thermogenesis. RNAscope technique identified a glutamatergic population of MnPO neurons that projects to the DMH and expresses c-Fos following cold exposure. These discoveries relative to the glutamatergic drive to BAT sympathoexcitatory neurons in DMH augment our understanding of the central thermoregulatory circuitry in non-torpid mammals. Our data will contribute to the development of novel therapeutic approaches to induce therapeutic hypothermia for treating drug-resistant fever, and for improving glucose and energy homeostasis.


2021 ◽  
Author(s):  
Zyanya Díaz-Hirashi ◽  
Tian Gao ◽  
Chiara Scaffidi ◽  
Monika Fey ◽  
Susan Murray ◽  
...  

Abstract Whole-body energy homeostasis is influenced by anabolic and catabolic cellular programs, which depend on environmental and nutritional cues. Adipose tissue plays a predominant role in the physiological regulation of energy balance by either storing or consuming energy through brown adipose tissue thermogenesis. It is however not clearly understood how brown adipose tissue balances catabolic and anabolic states. We show here that the transcription factor YY1 senses energetic state through a post-translational S120 phosphorylation switch. Adrenergic signaling leads to YY1 dephosphorylation which directly activates thermogenesis and a catabolic gene program while its phosphorylation maintains an anabolic program. Mechanistically, YY1 dephosphorylation increases chromatin binding at distal genomic loci respective to the transcription start site but remains constitutively bound to TSS. This mode of transcriptional control influences the activating and repressive function of YY1 and regulates catabolism/anabolism. We show that YY1 interacts with PPP1R3B, a regulatory subunit of the phosphatase PP1 and that in vivo knockdown of PPP1R3B protects against diet-induced obesity and insulin resistance. Our results uncover a novel transcriptional mechanism of metabolism orchestrated by YY1 phosphorylation switch and identifies PPP1R3B as a regulator of energy balance.


2012 ◽  
Vol 3 (4) ◽  
pp. 381-386 ◽  
Author(s):  
Christopher J. Madden ◽  
Domenico Tupone ◽  
Shaun F. Morrison

AbstractNon-shivering thermogenesis in brown adipose tissue (BAT) plays an important role in thermoregulation. In addition, activations of BAT have important implications for energy homeostasis due to the metabolic consumption of energy reserves entailed in the production of heat in this tissue. In this conceptual overview, we describe the role of orexins/hypocretins within the central nervous system in the modulation of thermogenesis in BAT under several physiological conditions. Within this framework, we consider potential neural mechanisms underlying the pathological conditions associated with the absence of the central orexinergic modulation of BAT thermogenesis and energy expenditure. Overall, the experimental basis for our understanding of the role of central orexin in regulating body temperature and energy homeostasis provides an illustrative example that highlights several general principles and caveats that should help guide future investigations of the neurochemical regulation of thermogenesis and metabolism.


Author(s):  
Soulmaz Shorakae ◽  
Eveline Jona ◽  
Courten Barbora de ◽  
Gavin Lambert ◽  
Elisabeth Lambert ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
L. Van Schaik ◽  
C. Kettle ◽  
R. Green ◽  
W. Sievers ◽  
M. W. Hale ◽  
...  

AbstractThe role of central orexin in the sympathetic control of interscapular brown adipose tissue (iBAT) thermogenesis has been established in rodents. Stimulatory doses of caffeine activate orexin positive neurons in the lateral hypothalamus, a region of the brain implicated in stimulating BAT thermogenesis. This study tests the hypothesis that central administration of caffeine is sufficient to activate BAT. Low doses of caffeine administered either systemically (intravenous [IV]; 10 mg/kg) and centrally (intracerebroventricular [ICV]; 5–10 μg) increases BAT thermogenesis, in anaesthetised (1.5 g/kg urethane, IV) free breathing male rats. Cardiovascular function was monitored via an indwelling intra-arterial cannula and exhibited no response to the caffeine. Core temperature did not significantly differ after administration of caffeine via either route of administration. Caffeine administered both IV and ICV increased neuronal activity, as measured by c-Fos-immunoreactivity within subregions of the hypothalamic area, previously implicated in regulating BAT thermogenesis. Significantly, there appears to be no neural anxiety response to the low dose of caffeine as indicated by no change in activity in the basolateral amygdala. Having measured the physiological correlate of thermogenesis (heat production) we have not measured indirect molecular correlates of BAT activation. Nevertheless, our results demonstrate that caffeine, at stimulatory doses, acting via the central nervous system can increase thermogenesis, without adverse cardio-dynamic impact.


Author(s):  
Ellen Paula Santos da Conceição Furber ◽  
Clarissa M.D. Mota ◽  
Edward Veytsman ◽  
Shaun F. Morrison ◽  
Christopher J. Madden

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.


Author(s):  
Soulmaz Shorakae ◽  
Eveline Jona ◽  
Barbora de Courten ◽  
Gavin W. Lambert ◽  
Elisabeth A. Lambert ◽  
...  

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