In situ assessment of the role of the β1, β2‐ and β3‐adrenoceptors in the control of lipolysis and nutritive blood flow in human subcutaneous adipose tissue

Barbe, P; Millet, L; Galitzky, Jean; Lafontan, Max; Berlan, Michel

doi:10.1111/j.1476-5381.1996.tb15279.x

Cited by 162 publications

(110 citation statements)

References 39 publications

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“…It must be emphasized that, while the ␤ 3 -AR plays a pivotal role in rodent white or brown adipose tissue, it is expressed at much lower levels in humans (48 -50). Recent studies performed in vivo have shown that the ␤ 3 -AR is able to mediate lipolysis in subcutaneous fat in humans (51,52), but its role appears secondary as compared with that of ␤ 1 -or ␤ 2 -ARs. It is thus likely that a potential regulation by TNF-␣ of the ␤ 3 -AR in human adipocytes would not cause marked functional consequences.…”

Section: Table IV Effect Of Tnf-␣ Treatment On the Lipolytic Activitymentioning

confidence: 99%

Differential Regulation by Tumor Necrosis Factor-α of β1-, β2-, and β3-Adrenoreceptor Gene Expression in 3T3-F442A Adipocytes

Hadri

Courtalon

Gauthereau

et al. 1997

Journal of Biological Chemistry

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Modulation of ␤-adrenoreceptor expression by tumor necrosis factor-␣ (TNF-␣) was investigated in murine 3T3-F442A adipocytes. TNF-␣ treatment of mature adipocytes decreased ␤ 3 -adrenoreceptor mRNA content in a time-and concentration-dependent manner, with a 8.5-fold decrease observed after a 6-h exposure to 300 pM TNF-␣. ␤ 1 -Adrenoreceptor mRNA abundance was slightly decreased by TNF-␣ treatment, while ␤ 2 -adrenoreceptor mRNA levels were potently induced (6-fold increase at 6 h). (؊)-[ 125 I]Iodocyanopindolol saturation and competition binding experiments indicated that TNF-␣ induced a 2-fold decrease in ␤ 3 -adrenoreceptor number, a nonsignificant reduction in ␤ 1 -subtype population, and a ϳ4.5-fold increase in ␤ 2 -adrenoreceptor density. This correlated with a lower EC 50 value measured for epinephrine in stimulating adenylyl cyclase, whereas the EC 50 value for norepinephrine increased. Nuclear run-on assays on isolated nuclei and mRNA stability measurements showed that TNF-␣ increased both ␤ 2 -adrenoreceptor gene transcription and ␤ 2 -adrenoreceptor mRNA half-life, while ␤ 1 -and ␤ 3 -adrenoreceptor gene expression was modulated only at the transcriptional level by the cytokine. These findings demonstrate a differential modulation by TNF-␣ of the three ␤-adrenoreceptor subtypes in adipocytes, which may contribute to metabolic disorders induced by the cytokine in the adipocyte.Tumor necrosis factor-␣ (TNF-␣) 1 is a multifunctional cytokine that was originally identified as a tumoricidal protein (1). Subsequent investigations have shown that TNF-␣ was fundamentally involved in control of the growth, differentiation, and metabolism in several normal cells and tissues.A sum of work has been focused on the role of TNF-␣ in the regulation of adipocyte development and metabolism (1, 2). Thus, TNF-␣ strongly inhibits adipose conversion and even causes a dramatic dedifferentiation of adipocytes in culture (3-6). Moreover, it is also documented that TNF-␣ decreases the synthesis and activity of several proteins essential for lipogenesis and triglyceride accumulation in adipocytes. These include lipoprotein lipase (5, 7-9), acetyl-coenzyme A carboxylase (4, 10, 11), acyl-coenzyme A synthetase (12), stearoyl-coenzyme A desaturase (12), and the insulin-sensitive glucose transporter GLUT4 (13,14).In addition to the above effects on adipogenesis and reduction of de novo fatty acid synthesis, TNF-␣ also depletes triglycerides from adipocytes by directly increasing lipolysis (15-17). So far, the molecular mechanism by which the cytokine potentiates lipolysis remains unclear (17).Through activation of three ␤-AR subtypes, catecholamines exert a key role in the regulation of lipid metabolism in adipocytes. They modulate cAMP-dependent processes such as lipolysis and the genetic control of the lipogenic and thermogenic pathways. As regards the pleiotropic effects of TNF-␣ on several metabolic pathways in adipocytes, and to the key role of the ␤-AR system in lipid mobilization, it is possible that an interplay between TNF...

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Section: Table IV Effect Of Tnf-␣ Treatment On the Lipolytic Activitymentioning

confidence: 99%

Differential Regulation by Tumor Necrosis Factor-α of β1-, β2-, and β3-Adrenoreceptor Gene Expression in 3T3-F442A Adipocytes

Hadri

Courtalon

Gauthereau

et al. 1997

Journal of Biological Chemistry

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“…Adrenergic receptors expressed within adipose tissue have been extensively studied. 78,79 Obesity is associated with changes in adrenoceptor numbers and subtypes. 80 This suggests that the autonomic signals to adipose tissue are modulated in response to energy stores and adipocyte size.…”

Section: Innervation Of White Adipose Tissuementioning

confidence: 99%

Integrative physiology of human adipose tissue

et al. 2003

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Adipose tissue is now recognised as a highly active metabolic and endocrine organ. Great strides have been made in uncovering the multiple functions of the adipocyte in cellular and molecular detail, but it is essential to remember that adipose tissue normally operates as a structured whole. Its functions are regulated by multiple external influences such as autonomic nervous system activity, the rate of blood flow and the delivery of a complex mix of substrates and hormones in the plasma. Attempting to understand how all these factors converge and regulate adipose tissue function is a prime example of integrative physiology. Adipose tissue metabolism is extremely dynamic, and the supply of and removal of substrates in the blood is acutely regulated according to the nutritional state. Adipose tissue possesses the ability to a very large extent to modulate its own metabolic activities, including differentiation of new adipocytes and production of blood vessels as necessary to accommodate increasing fat stores. At the same time, adipocytes signal to other tissues to regulate their energy metabolism in accordance with the body's nutritional state. Ultimately adipocyte fat stores have to match the body's overall surplus or deficit of energy. This implies the existence of one (or more) signal(s) to the adipose tissue that reflects the body's energy status, and points once again to the need for an integrative view of adipose tissue function.

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“…Much initial attention focussed on a role of β 3 -adrenoceptors in the regulation of adipocyte function, but later studies showed that its important role in rodents is not paralleled by a major role in human adipocytes (Barbe et al 1996;Rosenbaum et al 1993). Meanwhile, a role for β 3 -adrenoceptors has been established in blood vessels (Guimaraes and Moura 2001;Rozec and Gauthier 2006) and the urinary bladder (Michel and Vrydag 2006).…”

mentioning

confidence: 99%

Tools to study β3-adrenoceptors

Vrydag

Michel

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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In situ assessment of the role of the β₁, β₂‐ and β₃‐adrenoceptors in the control of lipolysis and nutritive blood flow in human subcutaneous adipose tissue

Cited by 162 publications

References 39 publications

Differential Regulation by Tumor Necrosis Factor-α of β1-, β2-, and β3-Adrenoreceptor Gene Expression in 3T3-F442A Adipocytes

Differential Regulation by Tumor Necrosis Factor-α of β1-, β2-, and β3-Adrenoreceptor Gene Expression in 3T3-F442A Adipocytes

Integrative physiology of human adipose tissue

Tools to study β3-adrenoceptors

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