scholarly journals Liraglutide Activates Type 2 Deiodinase and Enhances β3-Adrenergic-Induced Thermogenesis in Mouse Adipose Tissue

2022 ◽  
Vol 12 ◽  
Author(s):  
Fernanda C. B. Oliveira ◽  
Eduarda J. Bauer ◽  
Carolina M. Ribeiro ◽  
Sidney A. Pereira ◽  
Bruna T. S. Beserra ◽  
...  
Keyword(s):  
Weight Loss ◽  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Mrna Levels ◽  
Additive Effects ◽  
Adrenergic Stimulation ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Gene And Protein Expression

AimsLiraglutide is a long-acting glucagon-like peptide 1 (GLP-1) receptor agonist used as an anti-hyperglycemic agent in type 2 diabetes treatment and recently approved for obesity management. Weight loss is attributed to appetite suppression, but therapy may also increase energy expenditure. To further investigate the effect of GLP-1 signaling in thermogenic fat, we assessed adipose tissue oxygen consumption and type 2 deiodinase (D2) activity in mice treated with liraglutide, both basally and after β3-adrenergic treatment.MethodsMale C57BL/6J mice were randomly assigned to receive liraglutide (400 μg/kg, n=12) or vehicle (n=12). After 16 days, mice in each group were co-treated with the selective β3-adrenergic agonist CL316,243 (1 mg/kg, n=6) or vehicle (n=6) for 5 days. Adipose tissue depots were assessed for gene and protein expression, oxygen consumption, and D2 activity.ResultsLiraglutide increased interscapular brown adipose tissue (iBAT) oxygen consumption and enhanced β3-adrenergic-induced oxygen consumption in iBAT and inguinal white adipose tissue (ingWAT). These effects were accompanied by upregulation of UCP-1 protein levels in iBAT and ingWAT. Notably, liraglutide increased D2 activity without significantly upregulating its mRNA levels in iBAT and exhibited additive effects to β3-adrenergic stimulation in inducing D2 activity in ingWAT.ConclusionsLiraglutide exhibits additive effects to those of β3-adrenergic stimulation in thermogenic fat and increases D2 activity in BAT, implying that it may activate this adipose tissue depot by increasing intracellular thyroid activation, adding to the currently known mechanisms of GLP-1A-induced weight loss.

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

1991 ◽  
Vol 277 (3) ◽  
pp. 625-629 ◽  
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.

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.

Suppression of norepinephrine-induced thermogenesis in brown adipose tissue by fasting

1983 ◽  
Vol 245 (6) ◽  
pp. E582-E586 ◽  
Author(s):  
M. Hayashi ◽  
T. Nagasaka
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Thyroid Hormones ◽  
Brown Adipose Tissue ◽  
Plasma Levels ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Colonic Temperature ◽  
Induced Changes ◽  
Thermogenic Response

Fasting-induced changes in thermogenic responses to norepinephrine (NE, 4.0 micrograms X kg-1 X min-1 iv) were studied in anesthetized rats previously cold acclimated. The rats were divided into five groups at the end of 30–40 days of cold acclimation (5 degrees C). The five groups were kept for 5 days at 25 degrees C and fed (intact fed), fasted (intact fasted), fasted with daily treatment with thyroxine (T4, 2 micrograms/kg sc), thyroidectomized and fed, or thyroidectomized and fasted. In the intact fasted group, in which the weight of brown adipose tissue decreased, NE-induced increases in oxygen consumption, colonic temperature (T col), and temperature of the interscapular brown adipose tissue (TBAT) were markedly suppressed. The two thyroidectomized groups also showed a reduction in thermogenic response. In these three groups, TBAT was lower than Tcol throughout NE infusion. In the T4-treated fasted group, fasting-induced suppression of thermogenic response to NE was largely prevented. In the intact fed and the T4-treated fasted groups, TBAT attained higher values than Tcol during NE infusion. Plasma levels of thyroid hormones were significantly lower in the intact fasted group than in the intact fed or the T4-treated fasted group. These results suggest that fasting-induced suppression of the thermogenic response to NE is largely due to the reduced thermogenic response of brown adipose tissue to NE. The lowering of the levels of the thyroid hormones induced by fasting may be one of a number of causes of the reduction in the thermogenic response of brown adipose tissue.

Nesfatin-1 Acts Centrally to Induce Sympathetic Activation of Brown Adipose Tissue and Non-Shivering Thermogenesis

2019 ◽  
Vol 51 (10) ◽  
pp. 678-685 ◽  
Author(s):  
Luka Levata ◽  
Riccardo Dore ◽  
Olaf Jöhren ◽  
Markus Schwaninger ◽  
Carla Schulz ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Body Weight Loss ◽  
Whole Body ◽  
Central Administration ◽  
Adrenergic Stimulation ◽  
Interscapular Brown Adipose Tissue ◽  
Adrenoceptor Antagonist ◽  
Brown Adipose

AbstractNesfatin-1 has originally been established as a bioactive peptide interacting with key hypothalamic nuclei and neural circuitries in control of feeding behavior, while its effect on energy expenditure has only recently been investigated. Hence, the aim of this study was to examine whether centrally acting nesfatin-1 can induce β3-adrenergic stimulation, which is a prerequisite for the activation of thermogenic genes and heat release from interscapular brown adipose tissue, key physiological features that underlie increased energy expenditure. This question was addressed in non-fasted mice stereotactically cannulated to receive nesfatin-1 intracerebroventricularly together with peripheral injection of the β3-adrenoceptor antagonist SR 59230 A, to assess whole-body energy metabolism. Using a minimally invasive thermography technique, we now demonstrate that the thermogenic effect of an anorectic nesfatin-1 dose critically depends on β3 adrenergic stimulation, as the co-administration with SR 59230 A completely abolished heat production from interscapular brown adipose tissue and rise in ocular surface temperature, thus preventing body weight loss. Moreover, through indirect calorimetry it could be shown that the anorectic concentration of nesfatin-1 augments overall caloric expenditure. Plausibly, central administration of nesfatin-1 also enhanced the expression of DIO2 and CIDEA mRNA in brown adipose tissue critically involved in the regulation of thermogenesis.

Transient upregulation of IGF-I gene expression in brown adipose tissue of cold-exposed rats

1997 ◽  
Vol 272 (3) ◽  
pp. E453-E460 ◽  
Author(s):  
C. Duchamp ◽  
K. A. Burton ◽  
A. Geloen ◽  
M. J. Dauncey
Keyword(s):  
Adipose Tissue ◽  
Food Intake ◽  
Brown Adipose Tissue ◽  
Unit Weight ◽  
Mrna Levels ◽  
Interscapular Brown Adipose Tissue ◽  
Total Rna ◽  
Brown Adipose ◽  
Igf I

The possible involvement of locally produced insulin-like growth factor I (IGF-I) in the cold-induced hyperplasia of interscapular brown adipose tissue (BAT) was investigated in 2-, 4-, and 7-day cold-exposed (CE, 4 degrees C) rats by measuring BAT IGF-I expression at a time when extensive BAT cell proliferation occurs. By comparison with thermoneutral (25 degrees C) controls, plasma IGF-I decreased in CE rats despite an increased food intake, whereas BAT IGF-I peptide increased markedly to peak after 4 days at 4 degrees C. The ratio of class 1 to class 2 IGF-I mRNA was much higher in BAT than in liver. BAT IGF-I mRNA levels per unit weight total RNA doubled after 2 days at 4 degrees C but decreased thereafter to the level in controls. Upregulation of BAT IGF-I mRNA also occurred in CE rats with a food intake restricted to the level of controls. The transient cold-induced upregulation of BAT IGF-I (per unit weight total RNA) suggests that IGF-I plays a role in the early cold-induced BAT hyperplasia that occurs in vivo.

Energy balance following sympathetic denervation of brown adipose tissue

1984 ◽  
Vol 62 (2) ◽  
pp. 235-240 ◽  
Author(s):  
A. G. Dulloo ◽  
D. S. Miller
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Energy Balance ◽  
Brown Adipose Tissue ◽  
Body Fat ◽  
Metabolizable Energy ◽  
Energetic Efficiency ◽  
Interscapular Brown Adipose Tissue ◽  
Body Protein ◽  
Brown Adipose

The effects of sham, bilateral surgical denervation or excision of interscapular brown adipose tissue on body composition and energetic efficiency were studied in young CFLP mice kept at 25 °C and fed a laboratory stock diet. A preliminary experiment showed that 15 weeks following surgery, total body fat was increased by 42% in the denervated group and by 72% in the excised group while body protein was unchanged. In another 7-week energy balance experiment, body fat was also significantly higher by 15 and 18% in the denervated and excised group, respectively, but metabolizable energy intake was slightly lower than that of sham controls. Determination of energy expenditure both by the comparative carcass slaughter technique and by measurement of daily oxygen consumption showed that the metabolic rate was reduced in the denervated and excised groups. The capacity for thermogenesis, as measured by an increase in oxygen consumption following injections of noradrenaline (600 μg/kg body weight) was similar in all groups. These studies show that denervation or excision of interscapular brown adipose tissue causes an elevation in energetic efficiency, and indicates an important role of the sympathetic nervous system in the regulation of animal heat production by brown adipose tissue and in the overall control of thermogenesis.

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 Metabolic activity of brown, “beige,” and white adipose tissues in response to chronic adrenergic stimulation in male mice

2016 ◽  
Vol 311 (1) ◽  
pp. E260-E268 ◽  
Author(s):  
Sébastien M. Labbé ◽  
Alexandre Caron ◽  
Kanta Chechi ◽  
Mathieu Laplante ◽  
Roger Lecomte ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Metabolic Activity ◽  
Oxidative Activity ◽  
Acid Uptake ◽  
Adrenergic Stimulation ◽  
Brown Adipocytes ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Beige Adipocytes

Classical brown adipocytes such as those found in interscapular brown adipose tissue (iBAT) represent energy-burning cells, which have been postulated to play a pivotal role in energy metabolism. Brown adipocytes can also be found in white adipose tissue (WAT) depots [e.g., inguinal WAT (iWAT)] following adrenergic stimulation, and they have been referred to as “beige” adipocytes. Whether the presence of these adipocytes, which gives iWAT a beige appearance, can confer a white depot with some thermogenic activity remains to be seen. In consequence, we designed the present study to investigate the metabolic activity of iBAT, iWAT, and epididymal white depots in mice. Mice were either 1) kept at thermoneutrality (30°C), 2) kept at 30°C and treated daily for 14 days with an adrenergic agonist [CL-316,243 (CL)], or 3) housed at 10°C for 14 days. Metabolic activity was assessed using positron emission tomography imaging with fluoro-[18F]deoxyglucose (glucose uptake), fluoro-[18F]thiaheptadecanoic acid (fatty acid uptake), and [11C]acetate (oxidative activity). In each group, substrate uptakes and oxidative activity were measured in anesthetized mice in response to acute CL. Our results revealed iBAT as a major site of metabolic activity, which exhibited enhanced glucose and nonesterified fatty acid uptakes and oxidative activity in response to chronic cold and CL. On the other hand, beige adipose tissue failed to exhibit appreciable increase in oxidative activity in response to chronic cold and CL. Altogether, our results suggest that the contribution of beige fat to acute-CL-induced metabolic activity is low compared with that of iBAT, even after sustained adrenergic stimulation.

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