scholarly journals Adrenergic stimulation of lipoprotein lipase gene expression in rat brown adipocytes differentiated in culture: mediation via β3- and α1-adrenergic receptors

1997 ◽  
Vol 321 (3) ◽  
pp. 759-767 ◽  
Author(s):  
Pertti KUUSELA ◽  
Stefan REHNMARK ◽  
Anders JACOBSSON ◽  
Barbara CANNON ◽  
Jan NEDERGAARD
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Direct Effect ◽  
Mrna Levels ◽  
Adrenergic Stimulation ◽  
Brown Adipocytes ◽  
Brown Adipose ◽  
Lpl Gene

In order to investigate whether the positive effect of adrenergic stimulation on lipoprotein lipase (LPL) gene expression in brown adipose tissue is a direct effect on the brown adipocytes themselves, the expression of the LPL gene was investigated by measuring LPL mRNA levels in brown adipocytes, isolated as precursors from the brown adipose tissue of rats and grown in culture in a fully defined medium before experimentation. Addition of noradrenaline led to an enhancement of LPL gene expression; the mRNA levels increased as a linear function of time for at least 5 h and were finally approx. 3 times higher than in control cells, an increase commensurate with that seen in vivoin both LPL mRNA levels and LPL activity during physiological stimulation. The increase was dependent on transcription. The effect of noradrenaline showed simple MichaelisŐMenten kinetics with an EC50 of approx. 11 nM. β3-Agonists (BRL-37344 and CGP-12177) could mimic the effect of noradrenaline; the β1-agonist dobutamine and the β2-agonist salbutamol could not; the α1-agonist cirazoline had only a weak effect. The effect of noradrenaline was fully inhibited by the β-antagonist propranolol and was halved by the α1-antagonist prazosin; the α2-antagonist yohimbine was without effect. An increase in LPL mRNA level similar to (but not significantly exceeding) that caused by noradrenaline could also be induced by the cAMP-elevating agents forskolin and cholera toxin, and 8-Br-cAMP also increased LPL mRNA levels. The increase in LPL gene expression was not mediated via an increase in the level of an intermediary proteinaceous factor. It is concluded that the physiologically induced increase in LPL gene expression is a direct effect of noradrenaline on the brown adipocytes themselves, mediated via a dominant β3-adrenergic pathway and an auxillary α1-adrenergic pathway which converge at a regulatory point in transcriptional control.

scholarly journals Postnatal selective suppression of lipoprotein lipase gene expression in brown adipose tissue (relative to the expression of the gene for the uncoupling protein) is not due to adrenergic insensitivity: a possible specific inhibitory effect of colostrum

1996 ◽  
Vol 314 (1) ◽  
pp. 261-267 ◽  
Author(s):  
María-Jesus OBREGÓN ◽  
Barbara CANNON ◽  
Jan NEDERGAARD
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Uncoupling Protein ◽  
Mrna Levels ◽  
Selective Suppression ◽  
Brown Adipose ◽  
Adrenergic Antagonist ◽  
Lpl Gene

The levels of mRNA coding for the uncoupling protein (UCP) and for lipoprotein lipase (LPL) were monitored in the brown adipose tissue of newborn rat pups. At 5 h after birth, the mRNA levels of UCP and LPL were high in pups exposed singly to 28 °C and low in pups kept singly at thermoneutrality (36 °C); in pups staying with the dam, the UCP mRNA levels were intermediate. However, the LPL mRNA levels were lower in pups staying with the dam than in pups at 36 °C, implying that factors additional to environmental temperature influenced LPL gene expression. Injection of noradrenaline into pups at thermoneutrality (36 °C) led to increases in UCP and LPL gene expression, but noradrenaline injections had no further effect in cold-exposed pups. The adrenergic effects were mediated via β-adrenergic receptors. The cold-induced increases in both UCP and LPL gene expression were abolished by the β-adrenergic antagonist propranolol. Thus differences in adrenergic responsiveness could not explain the differential expression of the UCP and LPL genes observed in pups staying with the dam. The presence of a physiological suppressor was examined by feeding single pups at 28 °C with different foods: nothing, water, Intralipid, cow's milk, rat milk and rat colostrum. None of these agents led to suppression of UCP gene expression, but colostrum led to a selective suppression of LPL gene expression. It was concluded that the genes for UCP and LPL were responsive to adrenergic stimuli immediately after birth, and it is suggested that a component of rat colostrum can selectively suppress LPL gene expression.

Effect of hypothyroidism on adenylyl cyclase activity and subtype gene expression in brown adipose tissue

1997 ◽  
Vol 273 (2) ◽  
pp. R762-R767 ◽  
Author(s):  
A. Chaudhry ◽  
J. G. Granneman
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Adenylyl Cyclase ◽  
Regulation Of Gene Expression ◽  
Mrna Levels ◽  
Adrenergic Stimulation ◽  
Functional Responses ◽  
Synergistic Interactions ◽  
Brown Adipose

Brown adipose tissue (BAT) expresses several adenylyl cyclase (AC) subtypes, and adrenergic stimulation selectively upregulates AC-III gene expression. Previous studies have described synergistic interactions between the sympathetic nervous system (SNS) and 3,5,3'-triiodothyronine (T3) on the regulation of gene expression in BAT. Because adrenergic stimulation also increases the activity of BAT type II thyroxine 5'-deiodinase (DII) and local T3 generation is important for many functional responses in BAT, we examined the effects of thyroid hormone status on the expression of various AC subtypes. Hypothyroidism selectively increased AC-III mRNA levels in BAT but not in white adipose tissue. Of the other subtypes examined, hypothyroidism did not alter AC-VI mRNA levels and slightly reduced AC-IX mRNA levels in BAT. The increase in AC-III expression was paralleled by an increase in forskolin-stimulated AC activity in BAT membranes. Sympathetic denervation of BAT abolished the increase in both AC activity and AC-III mRNA expression produced by hypothyroidism, but did not affect the expression of other subtypes. Surgical denervation also prevented the induction of AC-III in the cold-stressed euthyroid rat, but injections of T3 failed to alter AC-III expression in intact or denervated BAT. Our results indicate that T3 does not directly affect expression of AC-III. Rather, hypothyroidism increases BAT AC-III expression indirectly via an increase in sympathetic stimulation. Furthermore, our results strongly indicate that the increase in AC activity in hypothyroid BAT is due to increased expression of AC-III.

Corticosterone inhibits uncoupling protein gene expression in brown adipose tissue

1993 ◽  
Vol 265 (1) ◽  
pp. E81-E87 ◽  
Author(s):  
A. Moriscot ◽  
R. Rabelo ◽  
A. C. Bianco
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Adrenergic Stimulation ◽  
Brown Adipose ◽  
Adrenalectomized Rats ◽  
Intact Rats

Uncoupling protein (UCP) mRNA levels were studied in the interscapular brown adipose tissue (BAT) of rats undergoing different manipulations of the adrenal function and BAT adrenergic stimulation. Adrenalectomy did not affect UCP mRNA levels for up to 8 days post-surgery. However, adrenalectomized rats underwent a greater increase in UCP mRNA levels (26%) than intact rats after 4 h of cold exposure. Administration of corticosterone (500 micrograms.100 g body wt-1.day-1 sc) to intact or adrenalectomized rats, kept at 28 degrees C, produced a marked decrease of UCP mitochondrial content and cellular mRNA levels in a time-dependent manner (30% by 12 h and 50% by 24 h). Pretreatment of intact rats with corticosterone virtually abolished the UCP mRNA response to cold and norepinephrine (NE). In contrast, when rats had been preexposed to cold for 96 h, the injection of corticosterone did not affect UCP mRNA. These results show that corticosterone is a powerful inhibitor of UCP gene expression in vivo. Corticosterone inhibits both basal gene expression at thermoneutrality and the response to adrenergic stimulation either by cold or exogenous NE, suggesting a direct action on BAT. The data further suggest that corticosterone inhibits the initial accumulation of UCP mRNA mediated by UCP gene transcription, rather than accelerating the degradation of UCP mRNA.

Regulation of expression of the lipoprotein lipase gene in brown adipose tissue

1992 ◽  
Vol 263 (3) ◽  
pp. E500-E506 ◽  
Author(s):  
J. R. Mitchell ◽  
A. Jacobsson ◽  
T. G. Kirchgessner ◽  
M. C. Schotz ◽  
B. Cannon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Mrna Level ◽  
Mrna Levels ◽  
Lipoprotein Lipase Activity ◽  
Lipase Gene ◽  
Lipoprotein Lipase Gene ◽  
Brown Adipose

The regulation of lipoprotein lipase gene expression in brown adipose tissue was studied. Rats were preacclimated to 21 degrees C. Exposure to cold (4 degrees C) resulted in a rapid increase in the level of lipoprotein lipase mRNA in the tissue. The level peaked (expressed per microgram total RNA) after approximately 8 h and then slowly declined. The increased lipoprotein lipase mRNA level was not due to an increased stability of the mRNA, but, in a transition event from a high to a low expression of the lipoprotein lipase gene, a transcription-dependent process was recruited that accelerated the breakdown of lipoprotein lipase mRNA. Norepinephrine injections increased lipoprotein lipase mRNA levels in the tissue; this effect was mediated via a beta-adrenergic receptor. The effect of cold could be mimicked by norepinephrine injections, and these two effects were not additive, indicating that the cold effect was mediated by norepinephrine. The lipoprotein lipase mRNA level was also increased by insulin injections (into fasted animals); thus an increase in lipoprotein lipase gene expression in brown adipose tissue may be induced via two different stimuli, which, intracellularly, would be mediated via different signaling systems. In all investigated conditions, the changes in lipoprotein lipase mRNA levels observed here were parallelled by alterations in lipoprotein lipase activity reported earlier from this laboratory. It was therefore concluded that, under the conditions studied, lipoprotein lipase activity in brown adipose tissue was primarily regulated at the transcriptional level.

scholarly journals Peroxisome Proliferator-Activated Receptors-α and -γ, and cAMP-Mediated Pathways, Control Retinol-Binding Protein-4 Gene Expression in Brown Adipose Tissue

Endocrinology ◽  
2012 ◽  
Vol 153 (3) ◽  
pp. 1162-1173 ◽  
Author(s):  
Meritxell Rosell ◽  
Elayne Hondares ◽  
Sadahiko Iwamoto ◽  
Frank J. Gonzalez ◽  
Martin Wabitsch ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Retinol Binding Protein ◽  
Peroxisome Proliferator ◽  
Brown Adipocytes ◽  
Retinol Binding Protein 4 ◽  
White Adipocytes ◽  
Brown Adipose ◽  
Rbp4 Gene

Retinol binding protein-4 (RBP4) is a serum protein involved in the transport of vitamin A. It is known to be produced by the liver and white adipose tissue. RBP4 release by white fat has been proposed to induce insulin resistance. We analyzed the regulation and production of RBP4 in brown adipose tissue. RBP4 gene expression is induced in brown fat from mice exposed to cold or treated with peroxisome proliferator-activated receptor (PPAR) agonists. In brown adipocytes in culture, norepinephrine, cAMP, and activators of PPARγ and PPARα induced RBP4 gene expression and RBP4 protein release. The induction of RBP4 gene expression by norepinephrine required intact PPAR-dependent pathways, as evidenced by impaired response of the RBP4 gene expression to norepinephrine in PPARα-null brown adipocytes or in the presence of inhibitors of PPARγ and PPARα. PPARγ and norepinephrine can also induce the RBP4 gene in white adipocytes, and overexpression of PPARα confers regulation by this PPAR subtype to white adipocytes. The RBP4 gene promoter transcription is activated by cAMP, PPARα, and PPARγ. This is mediated by a PPAR-responsive element capable of binding PPARα and PPARγ and required also for activation by cAMP. The induction of the RBP4 gene expression by norepinephrine in brown adipocytes is protein synthesis dependent and requires PPARγ-coactivator-1-α, which acts as a norepinephine-induced coactivator of PPAR on the RBP4 gene. We conclude that PPARγ- and PPARα-mediated signaling controls RBP4 gene expression and releases in brown adipose tissue, and thermogenic activation induces RBP4 gene expression in brown fat through mechanisms involving PPARγ-coactivator-1-α coactivation of PPAR signaling.

scholarly journals Interscapular brown adipose tissue denervation does not promote the oxidative activity of inguinal white adipose tissue in male mice

2018 ◽  
Vol 315 (5) ◽  
pp. E815-E824 ◽  
Author(s):  
Sébastien M. Labbé ◽  
Alexandre Caron ◽  
William T. Festuccia ◽  
Roger Lecomte ◽  
Denis Richard
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Glucose Uptake ◽  
White Adipose Tissue ◽  
Oxidative Activity ◽  
Substrate Uptake ◽  
Adrenergic Stimulation ◽  
Brown Adipocytes ◽  
Apparent Lack ◽  
Brown Adipose

Brown adipose tissue (BAT) thermogenesis is a key controller of energy metabolism. In response to cold or other adrenergic stimuli, brown adipocytes increase their substrate uptake and oxidative activity while uncoupling ATP synthesis from the mitochondrial respiratory chain activity. Brown adipocytes are found in classic depots such as in the interscapular BAT (iBAT). They can also develop in white adipose tissue (WAT), such as in the inguinal WAT (iWAT), where their presence has been associated with metabolic improvements. We previously reported that the induction of oxidative metabolism in iWAT is low compared with that of iBAT, even after sustained adrenergic stimulation. One explanation to this apparent lack of thermogenic ability of iWAT is the presence of an active iBAT, which may prevent the full activation of iWAT. In this study, we evaluated whether iBAT denervation-induced browning of white fat enhanced the thermogenic activity of iWAT following cold acclimation, under beta-3 adrenergic stimulation (CL 316,243). Following a bilateral denervation of iBAT, we assessed energy balance, evaluated the oxidative activity of iBAT and iWAT using 11C-acetate, and quantified the dynamic glucose uptake of those tissues using 2-deoxy-2-[18F]- fluoro-d-glucose. Our results indicate that despite portraying marked browning and mildly enhanced glucose uptake, iWAT of cold-adapted mice does not exhibit significant oxidative activity following beta-3 adrenergic stimulation in the absence of a functional iBAT. The present results suggest that iWAT is not readily recruitable as a thermogenic organ even when functional iBAT is lacking.

scholarly journals Differential adrenergic regulation of the gene expression of the β-adrenoceptor subtypes β1, β2 and β3 in brown adipocytes

2000 ◽  
Vol 347 (3) ◽  
pp. 643-651 ◽  
Author(s):  
Tore BENGTSSON ◽  
Barbara CANNON ◽  
Jan NEDERGAARD
Keyword(s):  
Gene Expression ◽  
Receptor Subtypes ◽  
Mrna Levels ◽  
Adrenergic Stimulation ◽  
Brown Adipocytes ◽  
Adrenergic Regulation ◽  
Receptor Mrna ◽  
Degradation Rates ◽  
Brown Adipose ◽  
Β Receptor

In brown adipocytes, fundamental cellular processes (cell proliferation, differentiation and apoptosis) are regulated by adrenergic stimulation, notably through β-adrenergic receptors. The presence of all three β-receptor subtypes has been demonstrated in brown adipose tissue. Due to the significance of the action of these receptors and indications that the subtypes govern different processes, the adrenergic regulation of the expression of the β1-, β2- and β3-adrenoceptor genes was examined in murine brown-fat primary cell cultures. Moderate levels of β1-receptor mRNA, absence of β2-receptor mRNA and high levels of β3-receptor mRNA were observed in mature brown adipocytes (day 6 in culture). Noradrenaline (norepinephrine) addition led to diametrically opposite effects on β1- (markedly enhanced expression) and β3-gene expression (full cessation of expression, as previously shown). β2-Gene expression was induced by noradrenaline, but only transiently (< 1 h). The apparent affinities (EC50) of noradrenaline were clearly different (7 nM for the β1-gene and≤ 1 nM for the β3-gene), as were the mediation pathways (solely via β3-receptors and cAMP for the β1-gene and via β3-receptors and cAMP, as well as via α1-receptors and protein kinase C, for the β3-gene). The half-lives of the corresponding mRNA species were very short but different (17 min for β1-mRNA and 27 min for β3-mRNA), and these degradation rates were not affected by noradrenaline, implying that the mRNA levels were controlled by transcription. Inhibition of protein synthesis also led to diametrically opposite effects on β1- and β3-gene expression, but - notably - these effects were congruent with the noradrenaline effects, implying that a common factor regulating β1-gene expression negatively and β3-gene expression positively could be envisaged. In conclusion, very divergent effects of adrenergic stimulation on the expression of the different β-receptor genes were found within one cell type, and no unifying concept of adrenergic control of β-receptor gene expression can be formulated, either concerning different cell types, or concerning the different β-receptor subtype genes.

scholarly journals Relationship of brown adipose tissue perfusion and function: a study through β2-adrenoreceptor stimulation

2016 ◽  
Vol 120 (8) ◽  
pp. 825-832 ◽  
Author(s):  
Laura Ernande ◽  
Kristin I. Stanford ◽  
Robrecht Thoonen ◽  
Haihua Zhang ◽  
Maëva Clerte ◽  
...  
Keyword(s):  
Blood Flow ◽  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Brown Adipose Tissue ◽  
Glucose Uptake ◽  
Direct Effect ◽  
Brown Adipocytes ◽  
Bat Activity ◽  
Brown Adipose

Brown adipose tissue (BAT) activation increases glucose and lipid consumption; as such, it is been considered as a potential therapy to decrease obesity. BAT is highly vascularized and its activation is associated with a necessary increase in blood flow. However, whether increasing BAT blood flow per se increases BAT activity is unknown. To examine this hypothesis, we investigated whether an isolated increase in BAT blood flow obtained by β2-adrenoreceptor (β2-AR) stimulation with salbutamol increased BAT activity. BAT blood flow was estimated in vivo in mice using contrast-enhanced ultrasound. The absence of direct effect of salbutamol on the function of isolated brown adipocytes was assessed by measuring oxygen consumption. The effect of salbutamol on BAT activity was investigated by measuring BAT glucose uptake in vivo. BAT blood flow increased by 2.3 ± 0.6-fold during β2-AR stimulation using salbutamol infusion in mice ( P = 0.003). β2-AR gene expression was detectable in BAT but was extremely low in isolated brown adipocytes. Oxygen consumption of isolated brown adipocytes did not change with salbutamol exposure, confirming the absence of a direct effect of β2-AR agonist on brown adipocytes. Finally, β2-AR stimulation by salbutamol increased BAT glucose uptake in vivo (991 ± 358 vs. 135 ± 49 ng glucose/mg tissue/45 min in salbutamol vs. saline injected mice, respectively, P = 0.046). In conclusion, an increase in BAT blood flow without direct stimulation of the brown adipocytes is associated with increased BAT metabolic activity. Increasing BAT blood flow might represent a new therapeutic target in obesity.

scholarly journals Postnatal recruitment of brown adipose tissue is induced by the cold stress experienced by the pups. An analysis of mRNA levels for thermogenin and lipoprotein lipase

1989 ◽  
Vol 259 (2) ◽  
pp. 341-346 ◽  
Author(s):  
M J Obregón ◽  
A Jacobsson ◽  
T Kirchgessner ◽  
M C Schotz ◽  
B Cannon ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cold Stress ◽  
Brown Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Uncoupling Protein ◽  
Mrna Levels ◽  
Rat Pups ◽  
Brown Adipose ◽  
Actin Mrna ◽  
Clear Increase

In order to investigate the postnatal recruitment process, gene expression in the brown adipose tissue of rat pups was followed during the first 20 h of life. In normal pups, the level of mRNA coding for the uncoupling protein thermogenin increased markedly but gradually within the first 24 h. Lipoprotein lipase and actin mRNA levels were relatively low and remained constant. In pups exposed to thermoneutral temperature (35 degrees C) for the first 12 h after birth, no increase in thermogenin mRNA or lipoprotein lipase mRNA was observed, whereas in pups exposed to 28 degrees C a clear increase in both thermogenin and lipoprotein lipase mRNA levels was found. Actin mRNA levels were not affected by the environmental temperature under these circumstances. It was concluded that the postnatal recruitment in brown adipose tissue is a consequence of the cold stress experienced by the newborn pups. Thus, postnatal recruitment is not ontogenically predetermined.

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