scholarly journals Farnesoid X Receptor Activation in Brain Alters Brown Adipose Tissue Function via the Sympathetic System

2022 ◽  
Vol 14 ◽  
Author(s):  
Benjamin Deckmyn ◽  
Dorothée Domenger ◽  
Chloé Blondel ◽  
Sarah Ducastel ◽  
Emilie Nicolas ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Receptor Activation ◽  
Farnesoid X Receptor ◽  
Metabolic Energy ◽  
Peripheral Organs ◽  
Glucose And Lipid Metabolism ◽  
Brown Adipose ◽  
The Central Nervous System

The nuclear bile acid (BA) receptor farnesoid X receptor (FXR) is a major regulator of metabolic/energy homeostasis in peripheral organs. Indeed, enterohepatic-expressed FXR controls metabolic processes (BA, glucose and lipid metabolism, fat mass, body weight). The central nervous system (CNS) regulates energy homeostasis in close interaction with peripheral organs. While FXR has been reported to be expressed in the brain, its function has not been studied so far. We studied the role of FXR in brain control of energy homeostasis by treating wild-type and FXR-deficient mice by intracerebroventricular (ICV) injection with the reference FXR agonist GW4064. Here we show that pharmacological activation of brain FXR modifies energy homeostasis by affecting brown adipose tissue (BAT) function. Brain FXR activation decreases the rate-limiting enzyme in catecholamine synthesis, tyrosine hydroxylase (TH), and consequently the sympathetic tone. FXR activation acts by inhibiting hypothalamic PKA-CREB induction of TH expression. These findings identify a function of brain FXR in the control of energy homeostasis and shed new light on the complex control of energy homeostasis by BA through FXR.

scholarly journals Farnesoid X Receptor activation in brain alters brown adipose tissue function via the sympathetic system

2021 ◽  
Author(s):  
Benjamin Deckmyn ◽  
Dorothee Domenger ◽  
sarah ducatsel ◽  
emilie nicolas ◽  
emilie dorchies ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Receptor Activation ◽  
Farnesoid X Receptor ◽  
Metabolic Energy ◽  
Peripheral Organs ◽  
Glucose And Lipid Metabolism ◽  
Brown Adipose ◽  
The Central Nervous System

Background and Prupose: The nuclear bile acid (BA) receptor farnesoid X receptor (FXR) is a major regulator of metabolic/energy homeostasis in peripheral organs. Indeed, enterohepatic-expressed FXR controls metabolic processes (BA, glucose and lipid metabolism, fat mass, body weight). The central nervous system (CNS) regulates energy homeostasis in close interaction with peripheral organs. While FXR has been reported to be expressed in the brain, its function has not been studied so far. Experimental Approach: We studied the role of FXR in brain control of energy homeostasis by treating wild-type and FXR-deficient mice by intracerebroventricular (ICV) injection with the reference FXR agonist GW4064. Key Results: Here we show that pharmacological activation of brain FXR modifies energy homeostasis by affecting brown adipose tissue (BAT) function. Brain FXR activation decreases the rate-limiting enzyme in catecholamine synthesis, tyrosine hydroxylase (TH), and consequently the sympathetic tone. FXR activation acts by inhibiting hypothalamic PKA-CREB induction of TH expression. Conclusions and Implication: These findings identify a function of brain FXR in the control of energy homeostasis and shed new light on the complex control of energy homeostasis by BA through FXR.

scholarly journals Orexin modulates brown adipose tissue thermogenesis

2012 ◽  
Vol 3 (4) ◽  
pp. 381-386 ◽  
Author(s):  
Christopher J. Madden ◽  
Domenico Tupone ◽  
Shaun F. Morrison
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Pathological Conditions ◽  
Brown Adipose ◽  
Brown Adipose Tissue Thermogenesis ◽  
The Central Nervous System ◽  
Conceptual Overview ◽  
Shivering Thermogenesis

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.

scholarly journals Impaired Thermogenesis and a Molecular Signature for Brown Adipose Tissue inId2Null Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Peng Zhou ◽  
Maricela Robles-Murguia ◽  
Deepa Mathew ◽  
Giles E. Duffield
Keyword(s):  
Adipose Tissue ◽  
Body Temperature ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Core Body Temperature ◽  
Specific Pattern ◽  
Molecular Signature ◽  
Brown Adipose ◽  
Core Body ◽  
The Impact

Inhibitor of DNA binding 2 (ID2) is a helix-loop-helix transcriptional repressor rhythmically expressed in many adult tissues. Our previous studies have demonstrated thatId2null mice have sex-specific elevated glucose uptake in brown adipose tissue (BAT). Here we further explored the role ofId2in the regulation of core body temperature over the circadian cycle and the impact ofId2deficiency on genes involved in insulin signaling and adipogenesis in BAT. We discovered a reduced core body temperature inId2−/− mice. Moreover, inId2−/− BAT, 30 genes includingIrs1,PPARs, andPGC-1s were identified as differentially expressed in a sex-specific pattern. These data provide valuable insights into the impact ofId2deficiency on energy homeostasis of mice in a sex-specific manner.

scholarly journals Integration of DIGE and Bioinformatics Analyses Reveals a Role of the Antiobesity Agent Tungstate in Redox and Energy Homeostasis Pathways in Brown Adipose Tissue

2007 ◽  
Vol 7 (2) ◽  
pp. 378-393 ◽  
Author(s):  
Sílvia Barceló-Batllori ◽  
Susana G. Kalko ◽  
Yaiza Esteban ◽  
Sílvia Moreno ◽  
María C. Carmona ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Bioinformatics Analyses ◽  
Brown Adipose

scholarly journals ACE2 Pathway Regulates Thermogenesis and Energy Metabolism

2021 ◽  
Author(s):  
Xi Cao ◽  
Tingting Shi ◽  
Chuanhai Zhang ◽  
Wanzhu Jin ◽  
Lini Song ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Knockout Mice ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Cold Stimulation ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
Pka Pathway

Identification of key regulators of energy homeostasis holds important therapeutic promise for metabolic disorders, such as obesity and diabetes. ACE2 cleaves angiotensin II (Ang II) to generate Ang-(1-7) which acts mainly through the Mas receptor. Here, we identify ACE2 pathway as a critical regulator in the maintenance of thermogenesis and energy expenditure. We found that ACE2 is highly expressed in brown adipose tissue (BAT) and that cold stimulation increases ACE2 and Ang-(1-7) levels in BAT and serum. ACE2 knockout mice (ACE2-/y), Mas knockout mice (Mas-/-), and the mice transplanted with brown adipose tissue from Mas-/- mice displayed impaired thermogenesis. In contrast, impaired thermogenesis of db/db obese diabetic mice and high-fat diet-induced obese mice were ameliorated by overexpression of ACE2 or continuous infusion of Ang-(1-7). Activation of ACE2 pathway was associated with improvement of metabolic parameters, including blood glucose, lipids and energy expenditure in multiple animal models. Consistently, ACE2 pathway remarkably enhanced the browning of white adipose tissue. Mechanistically, we showed that ACE2 pathway activated Akt/FoxO1 and PKA pathway, leading to induction of UCP1 and activation of mitochondrial function. Our data propose that adaptive thermogenesis requires regulation of ACE2 pathway and highlight novel therapeutic targets for the treatment of metabolic disorders.

scholarly journals Identification of PACAP-Expressing Neurons in the Hypothalamic Origins of Sympathetic Outflow Tracts Terminating in Brown Adipose Tissue of Mice

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A541-A541
Author(s):  
Ekaterina Filatov ◽  
Alex P Rudecki ◽  
Alina-Geta Constantin ◽  
Sarah Louise Gray
Keyword(s):  
Nervous System ◽  
Adipose Tissue ◽  
Cold Stress ◽  
Brown Adipose Tissue ◽  
Sympathetic Nerve ◽  
Energy Homeostasis ◽  
Sympathetic Nerve Activity ◽  
Sympathetic Outflow ◽  
Nerve Activity ◽  
Brown Adipose

Abstract Adaptive thermogenesis in brown adipose tissue is stimulated by the sympathetic nervous system (SNS) in response to cold stress. Using retrograde viral transneuronal tract tracers, previous studies have identified that the paraventricular nucleus (PVN), ventromedial hypothalamus (VMH), and median preoptic nucleus (MnPO) contain neurons that are part of sympathetic outflow tracts to brown adipose tissue, presumptively involved in SNS stimulation of interscapular brown adipose tissue (iBAT). Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) is a peptide hormone known to regulate energy homeostasis, acting in both the central (CNS) and peripheral nervous system (PNS). Mice lacking PACAP have impaired adrenergic-induced thermogenesis and a cold-sensitive phenotype. In the CNS, PACAP is highly expressed in the VMH, MnPO, and PVN of the hypothalamus. Injection of PACAP into the VMN increased core body temperature and sympathetic nerve activity to brown adipose tissue. While these studies show exogenous PACAP can activate sympathetic outflow tracts to brown adipose tissue, they do not confirm that endogenously expressed PACAP induces sympathetic nerve activity as an adaptive mechanism to cold stress, or if sympathetic outflow tracts originating in the hypothalamus express PACAP. We hypothesize that PACAP is expressed in neurons of sympathetic outflow tracts originating in the hypothalamus. To test this hypothesis, PACAP-eGFP transgenic mice were injected with the retrograde neural tracer, pseudorabies virus tagged with β-galactosidase (β-gal, PRV-BaBlu), in iBAT where postganglionic nerves innervate the tissue. Five-days post-infection, animals were culled, brains removed and cryosectioned. Neurons positive for green fluorescent protein (eGFP) and/or β-gal immunoreactivity (ir) were identified by immunohistochemistry in serial coronal and sagittal brain cryo-sections. Co-occurrence of eGFP-ir and β-gal-ir, inferred PACAP expressing neurons present in sympathetic outflow tracts (ImageJ). Co-occurrence was identified in several structures in the hypothalamus and thalamus. In conclusion, this study presents neuroanatomical evidence for populations of PACAPinergic neurons in the hypothalamus that are part of sympathetic outflow tracts to brown adipose tissue, providing further evidence of a central role for PACAP in regulating energy homeostasis.

scholarly journals Catalase deficiency facilitates the shuttling of free fatty acid to brown adipose tissue through lipolysis mediated by ROS during sustained fasting

2021 ◽  
Author(s):  
Raghbendra Kumar Dutta ◽  
Joon No Lee ◽  
Yunash Maharjan ◽  
Channy Park ◽  
Seong-Kyu Choe ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Redox Homeostasis ◽  
Ros Generation ◽  
Peroxisomal Enzyme ◽  
Triglyceride Accumulation ◽  
Brown Adipose

Abstract Background Fatty acids (FA) derived from adipose tissue and liver serve as the main fuel in thermogenesis of brown adipose tissue (BAT). Catalase, a peroxisomal enzyme, plays an important role in maintaining intracellular redox homeostasis by decomposing hydrogen peroxide to either water or oxygen that oxidize and provide fuel for cellular metabolism. Although the antioxidant enzymatic activity of catalase is well known, its role in the metabolism and maintenance of energy homeostasis has not yet been revealed. The present study investigated the role of catalase in lipid metabolism and thermogenesis during nutrient deprivation in catalase-knockout (KO) mice. Results We found that hepatic triglyceride accumulation in KO mice decreased during sustained fasting due to lipolysis through reactive oxygen species (ROS) generation in adipocytes. Furthermore, the free FA released from lipolysis were shuttled to BAT through the activation of CD36 and catabolized by lipoprotein lipase in KO mice during sustained fasting. Although the exact mechanism for the activation of the FA receptor enzyme is still unclear, we found that ROS generation in adipocytes mediated the shuttling of FA to BAT. Conclusions Taken together, our findings uncover the novel role of catalase in lipid metabolism and thermogenesis in BAT, which may be useful in understanding metabolic dysfunction.

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