Respective degree of expression of β1, β2‐ and β3‐adrenoceptors in human brown and white adipose tissues

Deng, Chunhua; Paoloni-Giacobino, Ariane; Kuehne, Françoise; Boss, Olivier; Revelli, Jean‐Pierre; Moinat, Madelaine; Cawthorne, Michael A.; Muzzin, Patrick; Giacobino, Jean‐Paul

doi:10.1111/j.1476-5381.1996.tb15488.x

Cited by 60 publications

(48 citation statements)

References 30 publications

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“…The ␤ 3 -adrenoceptor, which, in rodents, is considered an adipocyte-specific ␤-adrenoceptor subtype [39], was expressed in the CD34ϩ cells, although at a low level. The presence of the ␤ 3 -adrenoceptor had been reported in humans only in newborn BAT [40] and in infant BAT immortalized cells [41]. Finally, Cidea mRNA expression confirmed the brown adipocyte nature of the CD34ϩ cells.…”

Section: Discussionsupporting

confidence: 55%

A Reservoir of Brown Adipocyte Progenitors in Human Skeletal Muscle

et al. 2008

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Brown adipose tissue uncoupling protein-1 (UCP1) plays a major role in the control of energy balance in rodents. It has long been thought, however, that there is no physiologically relevant UCP1 expression in adult humans. In this study we show, using an original approach consisting of sorting cells from various tissues and differentiating them in an adipogenic medium, that a stationary population of skeletal muscle cells expressing the CD34 surface protein can differentiate in vitro into genuine brown adipocytes with a high level of UCP1 expression and uncoupled respiration. These cells can be expanded in culture, and their UCP1 mRNA expression is strongly increased by cell-permeating cAMP derivatives and a peroxisome-proliferator-activated receptor-␥ (PPAR␥) agonist. Furthermore, UCP1 mRNA was detected in the skeletal muscle of adult humans, and its expression was increased in vivo by PPAR␥ agonist treatment. All the studies concerning UCP1 expression in adult humans have until now been focused on the white adipose tissue. Here we show for the first time the existence in human skeletal muscle and the prospective isolation of progenitor cells with a high potential for UCP1 expression. The discovery of this reservoir generates a new hope of treating obesity by acting on energy dissipation.

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Section: Discussionsupporting

confidence: 55%

A Reservoir of Brown Adipocyte Progenitors in Human Skeletal Muscle

et al. 2008

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“…Thirdly, staining was especially pronounced in multilocular adipocytes of perirenal tissue from phaeochromocytoma patients, consistent with the higher expression of b 3 -adrenoceptor mRNA in brown compared to white adipocytes. 10,16 In contrast, expression of the b 1 -adrenoceptor is lower in brown than in white adipocytes, at least during the transformation of bovine perirenal adipose tissue from brown into white fat. 23 Lastly, staining was less in obese than in lean subjects but was restored to the level in lean subjects by treatment with ephedrine and caffeine.…”

Section: Discussionmentioning

confidence: 95%

“…The existence and role of b 3 -adrenoceptors in human adipocytes is more controversial, however. Most, 10 -14 although not all 15,16 workers have detected b 3 -adrenoceptor mRNA in human adipose tissue, but expression is some 50-fold lower than in rodent adipose tissue 13,14 and b 3 -adrenoceptor transcripts represent less than 20% of total b-adrenoceptor transcripts compared with more than 90% in rodents. 12 Studies in transgenic mice indicate that the promoter for the human b 3 -adrenoceptor drives expression mainly in brown adipose tissue, of which there is relatively little in adult humans.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical identification of the β3-adrenoceptor in intact human adipocytes and ventricular myocardium: effect of obesity and treatment with ephedrine and caffeine

et al. 2002

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OBJECTIVES:To investigate whether the b 3 -adrenoceptor could be identified by immunohistochemistry in intact human white and brown adipocytes and other human tissues, and to investigate the influence of obesity and its treatment with ephedrine and caffeine on the expression of the b 3 -adrenoceptor in adipocytes. METHODS: Morbidly obese patients were given a hypoenergetic diet (70% of energy expenditure) and some were also treated with ephedrine and caffeine (20=200 mg, three times daily) for 4 weeks. Adipose tissue and other tissues were taken during surgery. Immunohistochemistry was carried out using a monoclonal antibody raised against the human b 3 -adrenoceptor. RESULTS: Staining was localized to the periphery of cells. All white adipocytes were stained. Those from lean subjects and obese subjects treated with ephedrine and caffeine showed more intense staining than those from untreated obese subjects. Staining was more intense in brown than in white adipocytes in perirenal adipose tissue from phaeochromocytoma patients. Staining was also seen in ventricular myocardium, and in smooth muscle of the prostate, ileum, colon and gall bladder. DISCUSSION: The tissue and subcellular distribution of staining was consistent with it being due to binding of the antibody to the human b 3 -adrenoceptor. The presence of the b 3 -adrenoceptor in human white adipocytes is consistent with evidence that it can mediate lipolysis in human white adipocytes. The increased expression of the b 3 -adrenoceptor in obese subjects treated with caffeine and ephedrine supports the potential of b 3 -adrenoceptor agonists in the treatment of obesity and type 2 diabetes. Its expression in ventricular myocardium is consistent with evidence that the b 3 -adrenoceptor mediates a negative inotropic effect in this tissue.

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“…To what extent β 3 -adrenoceptor mRNA is expressed in human adipose tissue has remained controversial (Berkowitz et al 1995;Deng et al 1996). In rats, β 3 -adrenoceptor mRNA has mainly been found in adipocytes, various parts of the gastrointestinal tract (Evans et al 1996;Granneman et al 1991), and also in the urinary bladder (Seguchi et al 1998).…”

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confidence: 99%

Tools to study β3-adrenoceptors

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2007

Naunyn-Schmied Arch Pharmacol

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β 3 -adrenoceptors mediate some of the effects of catecholamines on tissues such as blood vessels or the urinary bladder and are putative targets for the treatment of diseases such as the overactive bladder syndrome. Progress in the understanding of the presence, function, and regulation of β 3 -adrenoceptors has been hampered by a lack of highly specific tools. "Classical" is not selective for β 3 -adrenoceptors, at least in humans, and may actually be a partial agonist. Radioligands, which are suitable either for the selective labeling of β 3 -adrenoceptors or for the nonselective labeling of all β-adrenoceptor subtypes, are also missing. β 3 -and β 1 /β 2 double knockout mice have been reported, but their usefulness for extrapolations in humans is questionable based upon major differences between humans and rodents with regard to the ligand recognition and expression profiles of β 3 -adrenoceptors. While the common availability of more selective agonists and antagonists at the β 3 -adrenoceptor is urgently awaited, the limitations of the currently available tools need to be considered in studies of β 3 -adrenoceptor for the time being.

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Respective degree of expression of β₁, β₂‐ and β₃‐adrenoceptors in human brown and white adipose tissues

Cited by 60 publications

References 30 publications

A Reservoir of Brown Adipocyte Progenitors in Human Skeletal Muscle

A Reservoir of Brown Adipocyte Progenitors in Human Skeletal Muscle

Immunohistochemical identification of the β3-adrenoceptor in intact human adipocytes and ventricular myocardium: effect of obesity and treatment with ephedrine and caffeine

Tools to study β3-adrenoceptors

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