Acute cold exposure-induced down-regulation of CIDEA, cell death-inducing DNA fragmentation factor-α-like effector A, in rat interscapular brown adipose tissue by sympathetically activated β3-adrenoreceptors

Shimizu, Takahiro; Yokotani, Kunihiko

doi:10.1016/j.bbrc.2009.06.147

Cited by 12 publications

(11 citation statements)

References 30 publications

(34 reference statements)

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“…Beta-3 adrenoceptors have been shown to be involved in uncoupling protein 1 (UCP1) upregulation and BAT thermogenesis in isolated brown adipocyte or cell culture preparations (10,56,57). Upregulation of UCP1 elicited by a beta-3 agonist (in vitro study) or by cold exposure (in vivo study) is inhibited by SR59230A (46,52). In awake UCP-1-ablated mice, thermogenesis elicited by beta-3 agonists is blunted (18).…”

Section: Discussionmentioning

confidence: 96%

SR59230A, a beta-3 adrenoceptor antagonist, inhibits ultradian brown adipose tissue thermogenesis and interrupts associated episodic brain and body heating

Ootsuka

Kulasekara

Menezes

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Brown adipose tissue (BAT) thermogenesis occurs episodically in an ultradian manner approximately every 80-100 min during the waking phase of the circadian cycle, together with highly correlated increases in brain and body temperatures, suggesting that BAT thermogenesis contributes to brain and body temperature increases. We investigated this in conscious Sprague-Dawley rats by determining whether inhibition of BAT thermogenesis via blockade of beta-3 adrenoceptors with SR59230A interrupts ultradian episodic increases in brain and body temperatures and whether SR59230A acts on BAT itself or via sympathetic neural control of BAT. Interscapular BAT (iBAT), brain, and body temperatures, tail artery blood flow, and heart rate were measured in unrestrained rats. SR59230A (1, 5, or 10 mg/kg ip), but not vehicle, decreased iBAT, body, and brain temperatures in a dose-dependent fashion (log-linear regression P < 0.01, R(2) = 0.3, 0.4, and 0.4, respectively, n = 10). Ultradian increases in BAT, brain, and body temperature were interrupted by administration of SR59230A (10 mg/kg ip) compared with vehicle, resuming after 162 ± 24 min (means ± SE, n = 10). SR59230A (10 mg/kg ip) caused a transient bradycardia without any increase in tail artery blood flow. In anesthetized rats, SR59230A reduced cooling-induced increases in iBAT temperature without affecting cooling-induced increases in iBAT sympathetic nerve discharge. Inhibition of BAT thermogenesis by SR59230A, thus, reflects direct blockade of beta-3 adrenoceptors in BAT. Interruption of episodic ultradian increases in body and brain temperature by SR59230A suggests that BAT thermogenesis makes a substantial contribution to these increases.

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Section: Discussionmentioning

confidence: 96%

SR59230A, a beta-3 adrenoceptor antagonist, inhibits ultradian brown adipose tissue thermogenesis and interrupts associated episodic brain and body heating

Ootsuka

Kulasekara

Menezes

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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“…In the cold exposure protocol, hemi-denervated control and rosiglitazone-treated rats were either maintained at 23°C or transferred to a cold room (5°C) for 24 h with a similar light-dark cycle and free access to water and food. Such exposure is sufficient to trigger BAT sympathetic activity and UCP1 expression (13,32).…”

Section: Methodsmentioning

confidence: 98%

“…CIDEA is a mitochondrial protein highly expressed in BAT that interacts with and inhibits UCP1 uncoupling activity (42). CIDEA levels are downregulated by cold exposure, such effect being mediated by the sympathetic drive to BAT (32). The present findings suggest that, in addition to a reduced BAT sympathetic activity and thyroid status (12), CIDEA upregulation may be implicated in the absence of translation of the increased BAT mass and UCP1 content into higher functional thermogenic activity and energy expenditure on PPAR-␥ ligand treatment (22,27,36).…”

Section: Discusssionmentioning

confidence: 99%

Basal adrenergic tone is required for maximal stimulation of rat brown adipose tissue UCP1 expression by chronic PPAR-γ activation

Festuccia

Blanchard

Richard

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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We investigated the involvement of basal sympathetic tone in brown adipose tissue (BAT) recruitment and gene expression profile induced by peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation. Innervated and surgically denervated BAT pads of rats treated or not with rosiglitazone (15 mg.kg(-1).day(-1), 7 days) were evaluated for weight, triacylglycerol (TAG) and DNA content, mitochondrial mass, and gene expression. Rosiglitazone induced BAT recruitment (increased mass, TAG and DNA content) and mRNA levels of lipolytic (adipose tissue triglyceride lipase and CGI58) and lipogenic (lipoprotein lipase, phosphoenolpyruvate carboxykinase, fatty acid binding protein 4, and diacylglycerol acyltransferase 1) proteins independently of tissue innervation status. Mitochondrial mass and mRNA levels of its regulators peroxisome proliferator-activated receptor coactivator-alpha and CCAAT/enhancer binding protein-beta were not affected by rosiglitazone, while being significantly reduced by denervation. By contrast, maximal stimulation of uncoupling protein 1 (UCP1) (thermogenesis), cell death-inducing DNA fragmentation factor-45-like effector A (inhibitor of UCP1 activity), monoacylglycerol lipase (lipolysis), small heterodimer partner (transcription), and glycerokinase (TAG synthesis) by rosiglitazone depended on the presence of intact BAT innervation. Cold exposure (5 degrees C, 24 h) significantly increased UCP1 mRNA levels in innervated BAT pads of untreated rats, without affecting the already high BAT UCP1 levels of rosiglitazone-treated animals. A similar pattern of response was found in denervated pads, but with markedly lower UCP1 expression than that in innervated BAT. In conclusion, whereas the mass (hyperplasia and hypertrophy), lipogenic, and lipolytic components of BAT recruitment induced by rosiglitazone occur independently of tissue sympathetic innervation, maximal UCP1 expression induced by PPAR-gamma in vivo depends on the presence of basal BAT adrenergic tone. The residual sympathetic tone found under rosiglitazone treatment is, therefore, involved in the modulation of a subset of major components of PPAR-gamma-mediated BAT recruitment.

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“…Interestingly, Cidea, a lipid droplet protein that also negatively regulates brown fat metabolism (4,21,34), displays a similar pattern of regulation. Cidea expression in the brown fat cells is suppressed by cold exposure through ␤3-adrenergic signaling (27) but not in brown fat cells in vitro (our unpublished data).…”

Section: Discussionmentioning

confidence: 99%

RNF34 Is a Cold-Regulated E3 Ubiquitin Ligase for PGC-1α and Modulates Brown Fat Cell Metabolism

Wei

Pan

Mao

et al. 2012

Molecular and Cellular Biology

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The transcriptional coactivator PGC-1␣ is a master regulator of energy metabolism and adaptive thermogenesis in the brown fat cell. PGC-1␣ is a short-lived protein, and the molecular components that control PGC-1␣ turnover and their functional importance in energy metabolism are largely unknown. Here we performed a luciferase-based overexpression screen and identified a Ring-finger-containing protein, RNF34, as a specific E3 ubiquitin ligase for PGC-1␣. RNF34 is a nuclear protein that interacts with and ubiquitinates PGC-1␣ to promote its turnover. Interestingly, RNF34 binds to the C-terminal half of PGC-1␣ and targets it for degradation independently of the previously identified N-terminal phosphodegron motif. In brown fat cells, knockdown of RNF34 increases the endogenous PGC-1␣ protein level, uncoupling protein 1 (UCP1) expression, and oxygen consumption, while the opposite effects are observed in brown fat cells ectopically expressing wild-type RNF34 but not in cells expressing the ligase activity-defective mutant. Moreover, cold exposure and ␤3-adrenergic receptor signaling, conditions that induce PGC-1␣ expression, suppress RNF34 expression in the brown fat cell, indicating a physiological relevance of this E3 ligase in thermogenesis. Our results reveal that RNF34 is a bona fide E3 ubiquitin ligase for PGC-1␣ and negatively regulates brown fat cell metabolism. Metabolic programs are to a large extent controlled at the transcriptional level, in which the transcriptional coactivator PGC-1␣ is at the central node. Through its interaction with and coactivation of functionally distinct transcription factors, PGC-1␣ regulates tissue-specific metabolic pathways, including mitochondrial oxidative metabolism and adaptive thermogenesis in the brown fat cell, gluconeogenesis in the liver, and mitochondrial oxidative metabolism and muscle fiber specification in the skeletal muscle (13,20,23). The functions of PGC-1␣ in these tissues are highly coordinated with environmental cues and/or internal nutrient levels and are modulated by several mechanisms (6, 23). For example, in the brown fat cell, in response to cold exposure, transcription of PGC-1␣ mRNA is robustly induced, which leads to increased uncoupling protein 1 (UCP1) expression and heat production (14,20). More recently, we identified the transcriptional regulator twist-1 as a negative-feedback component that interacts with and directly antagonizes PGC-1␣ activity in the brown fat cell (18).Posttranslational modification of PGC-1␣ is another key mechanism that fine-tunes PGC-1␣'s function (6, 23). Phosphorylation and acetylation are the two best-characterized modifications to PGC-1␣, and their functional impacts have been studied in skeletal muscle cells and/or liver cells. Phosphorylation of PGC-1␣ by AMPK and p38 mitogen-activated protein kinase (MAPK) increases PGC-1␣ activity and enhances mitochondrial oxidative metabolism in skeletal muscle cells (9,19). On the other hand, phosphorylation by Akt and Clk2 suppresses PGC-1␣ activity and reduces hepatic gluco...

show abstract

Acute cold exposure-induced down-regulation of CIDEA, cell death-inducing DNA fragmentation factor-α-like effector A, in rat interscapular brown adipose tissue by sympathetically activated β3-adrenoreceptors

Cited by 12 publications

References 30 publications

SR59230A, a beta-3 adrenoceptor antagonist, inhibits ultradian brown adipose tissue thermogenesis and interrupts associated episodic brain and body heating

SR59230A, a beta-3 adrenoceptor antagonist, inhibits ultradian brown adipose tissue thermogenesis and interrupts associated episodic brain and body heating

Basal adrenergic tone is required for maximal stimulation of rat brown adipose tissue UCP1 expression by chronic PPAR-γ activation

RNF34 Is a Cold-Regulated E3 Ubiquitin Ligase for PGC-1α and Modulates Brown Fat Cell Metabolism

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