Adrenoceptors in white, brown, and brite adipocytes

Evans, Bronwyn A; Merlin, Jon; Bengtsson, Tore; Hutchinson, Dana S.

doi:10.1111/bph.14631

Cited by 56 publications

(79 citation statements)

References 161 publications

(261 reference statements)

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“…The receptors of the SNS can be divided into two main types based on their function, the ␣and the ␤-adrenoreceptors (ARs). There are at least two types of ␣-ARs, ␣1-AR and ␣2-AR, and there are three types of ␤-ARs, ␤1-, ␤2-, and ␤3-ARs (70,71). The ␣-AR and ␤-AR differ in their specificity for coupling to the heterotrimeric G-proteins, which results in complex and multidimensional stimulatory and inhibitory signaling pathways.…”

Section: Adrenergic Receptorsmentioning

confidence: 99%

“…␣1-ARs couple mainly to G␣ q/11 proteins that activate phospholipase C to generate inositol trisphosphate and diacylglycerol. These two second messengers increase intracellular Ca 2ϩ and protein kinase C, respectively, which stimulate a myriad of intracellular processes specific to each distinct cell type (70,71). In contrast, ␣2-AR couples primarily to G␣ i/o to inhibit adenylyl cyclase.…”

Section: Adrenergic Receptorsmentioning

confidence: 99%

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Opportunities and challenges in the therapeutic activation of human energy expenditure and thermogenesis to manage obesity

Chen

Brychta

Sater

et al. 2020

Journal of Biological Chemistry

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The current obesity pandemic results from a physiological imbalance in which energy intake chronically exceeds energy expenditure (EE), and prevention and treatment strategies remain generally ineffective. Approaches designed to increase EE have been informed by decades of experiments in rodent models designed to stimulate adaptive thermogenesis, a long-term increase in metabolism, primarily induced by chronic cold exposure. At the cellular level, thermogenesis is achieved through increased rates of futile cycling, which are observed in several systems, most notably the regulated uncoupling of oxidative phosphorylation from ATP generation by uncoupling protein 1, a tissue-specific protein present in mitochondria of brown adipose tissue (BAT). Physiological activation of BAT and other organ thermogenesis occurs through β-adrenergic receptors (AR), and considerable effort over the past 5 decades has been directed toward developing AR agonists capable of safely achieving a net negative energy balance while avoiding unwanted cardiovascular side effects. Recent discoveries of other BAT futile cycles based on creatine and succinate have provided additional targets. Complicating the current and developing pharmacological-, cold-, and exercise-based methods to increase EE is the emerging evidence for strong physiological drives toward restoring lost weight over the long term. Future studies will need to address technical challenges such as how to accurately measure individual tissue thermogenesis in humans; how to safely activate BAT and other organ thermogenesis; and how to sustain a negative energy balance over many years of treatment.

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Section: Adrenergic Receptorsmentioning

confidence: 99%

Section: Adrenergic Receptorsmentioning

confidence: 99%

Opportunities and challenges in the therapeutic activation of human energy expenditure and thermogenesis to manage obesity

Chen

Brychta

Sater

et al. 2020

Journal of Biological Chemistry

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“…In rodents, all three β-adrenoceptor subtypes are expressed in subcutaneous and visceral adipose depots with the β3-adrenoceptor being the main responsible for βadrenoceptor-mediated lipolysis in mature white adipocytes [42]. In human white adipocytes, expression of β3-adrenoceptors is not as relevant as the other subtypes [42].…”

Section: Discussionmentioning

confidence: 99%

“…More interestingly, human mature adipocytes differentiated in the presence of NT3 exhibit a higher expression of UCP-1, the major determinant of non-shivering thermogenesis and a characteristic marker of mature brown and brite adipocytes. The ability to drive uncoupled respiration through UCP-1 activation represents a possibility in the treatment of metabolic disorders by expending excess energy as dissipated heat [42,46]. The ability to induce an increase in the expression of UCP-1 is the first consequence of the activation of β-adrenoceptors, especially the β3 subtype.…”

Section: Nt3 Stimulates Lipolysis Decreases Adipocyte Size and Incrementioning

confidence: 99%

NT3/TrkC pathway modulates the expression of UCP-1 and adipocyte size in human and murine adipose tissue

Bové

Montó

Guillem-Llobat

et al. 2020

Preprint

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NT3, through activation of its tropomyosin-related kinase receptor C (TrkC), modulates neuronal survival and neural stem cell differentiation. It is widely distributed in peripheral tissues (specially vessels and pancreas) and this ubiquitous pattern suggests a role for NT3, outside the nervous system and related to metabolic functions. The presence of the NT3/TrkC pathway in the adipose tissue (AT) has never been investigated. Present work studies in human and murine adipose tissue (AT) the presence of elements of the NT3/TrkC pathway and its role on lipolysis and adipocyte differentiation. qRT-PCR and immunoblot indicate that NT3 was present in human retroperitoneal AT and decreases with age. NT3 was also present in rat isolated adipocytes and retroperitoneal, interscapular, perivascular and perirenal AT. Histological analysis evidences that NT3 was mainly present in vessels irrigating AT close associated to sympathetic fibers. Similar mRNA levels of TrkC and β-adrenoceptors were found in all ATs assayed and in isolated adipocytes. NT3, through TrkC activation, exert a mild effect in lipolysis. Addition of NT3 during the differentiation process of human pre-adipocytes resulted in smaller adipocytes and increased uncoupling protein-1 (UCP-1) without changes in β-adrenoceptors. Similarly, transgenic mice with reduced expression of NT3 (Ntf3 knock-in lacZ reporter mice) or lacking endothelial NT3 expression (Ntf3flox1/flox2;Tie2-Cre+/0) displayed enlarged white and brown adipocytes and lower UCP-1 expression.ConclusionsNT3, mainly released by blood vessels, activates TrkC and regulates adipocyte differentiation and browning. Disruption of NT3/TrkC signaling conducts to hypertrophied white and brown adipocytes with reduced expression of the thermogenesis marker UCP-1

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“…Subsequently, Gas proteins are coupled by β3-adrenoceptors and activate adenylate cyclase (AC) to enhance cyclic AMP (cAMP) levels followed by the protein kinase A activation and phosphorylation of p38 mitogen-activated protein kinases (p-p38MAPK). P-p38MAPK phosphorylates PPARγ cofactor-1α (PGC-1α), cAMP response element-binding protein and activating transcription factor 2 to increase UCP1 protein levels for a greater mitochondrial uncoupling capacity (3,(41)(42)(43). Multiple agents such as β3-adrenoceptor agonist and PPARγ agonists are also able to induce browning of white adipose tissue (3,5,14,26,44)}.…”

Section: Introductionmentioning

confidence: 99%

Beige adipocytes independently improve impaired glucose metabolism in the absence of brown adipose tissues in vivo

Jia

Fang

et al. 2020

Preprint

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Beige adipocytes are emerging as an interesting issue in obesity and metabolism research. There is a neglected possibility that brown adipocytes are equally activated when external stimuli induce beige adipocytes. Thus, a question is whether beige adipocytes have the same functions as brown adipocytes when brown adipose tissue (BAT) is lacking. This question has not been well studied. Therefore we determine the beneficial effects of beige adipocytes upon cold challenge or CL316243 treatments in animal models of BAT ablation by surgical denervation. The data show that beige adipocytes partly contribute to impaired glucose metabolism resulting from denervated BAT. Whereas, we found that denervated BAT were activated by cold exposure and CL316243. Thus, we further used BAT-removal animal models to abolish BAT functions completely. We found that beige adipocytes upon cold challenge or CL316243 treatments independently improved impaired glucose metabolism in BAT-removal mice. The insulin signaling was activated in BAT-removal mice upon cold exposure. Whereas, both the activation of insulin signaling and up-regulation of glucose transporter expression were observed in BAT-removal mice with CL316243 treatments. The data show that beige adipocytes induced by cold exposure or CL316243 may have different mechanisms to improve impaired glucose metabolism. Beige adipocytes can also enhance energy expenditure and lipolytic activity of white adipose tissue when BAT is lacking. We provide direct evidences for the beneficial effect of beige adipocytes in glucose metabolism and energy expenditure in the absence of BAT in vivo.

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Adrenoceptors in white, brown, and brite adipocytes

Cited by 56 publications

References 161 publications

Opportunities and challenges in the therapeutic activation of human energy expenditure and thermogenesis to manage obesity

Opportunities and challenges in the therapeutic activation of human energy expenditure and thermogenesis to manage obesity

NT3/TrkC pathway modulates the expression of UCP-1 and adipocyte size in human and murine adipose tissue

Beige adipocytes independently improve impaired glucose metabolism in the absence of brown adipose tissues in vivo

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