Catecholamines suppress leptin release from in vitro differentiated subcutaneous human adipocytes in primary culture via beta1- and beta2-adrenergic receptors.
OBJECTIVE
Circulating leptin, the product of the ob gene, is known to be closely correlated with adipose tissue mass, but it is also subject to short-term regulation by a variety of hormones including catecholamines. The aim of this study was to investigate the contribution of the three beta-adrenergic receptors to leptin secretion from cultured human adipocytes.


METHODS
The model of in vitro differentiated human subcutaneous adipocytes was used in this study. The presence of the beta-adrenoceptor subtypes was studied by RT-PCR. The functional role of the receptor subtypes was determined by stimulation of lipolysis by selective beta-adrenergic agonists and by measuring glycerol release. Leptin secretion into the medium of cultured human adipocytes from young normal-weight females was measured by radioimmunoassay.


CONCLUSIONS
In a first set of experiments, the expression of the three beta-adrenergic receptor subtypes in cultured human adipocytes was demonstrated. To test their functional activity, the effect of the beta-adrenoceptor agonists isoproterenol (non-selective agonist), dobutamine (beta(1)-selective), fenoterol (beta(2)-selective) and the beta(3)-selective agonists BRL 37344 and CGP 12177 was studied. All agonists exhibited a dose- and time-dependent stimulation of glycerol release into the medium in a rather uniform manner. Isoproterenol rapidly reduced leptin secretion from cultured subcutaneous adipocytes in a dose-dependent fashion. Incubation with 10(-6)mol/l isoproterenol for 24h resulted in a reduction of the leptin concentration by 48% (P < 0.01). A similar, but less pronounced suppressing effect was seen for dobutamine and fenoterol, whereas both BRL 37344 and CGP 12177 were not effective. These data provide evidence that catecholamines are able to suppress leptin release from differentiated human adipocytes, supporting the concept that leptin secretion is acutely regulated by surrounding hormones. This inhibition is obviously mediated via beta(1)- and beta(2)-adrenergic receptors.
Scriba
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German Diabetes Research Institute at the Heinrich-Heine-University Düsseldorf, Clinical Department, D-40225 Düsseldorf, Germany.
Aprath-Husmann
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Blum
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WF
Hauner
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D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D002395:Catecholamines / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D003864:Depression, Chemical; D005260:Female; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D008066:Lipolysis / Q000187:drug effects; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism*; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D003470:Culture Media; C515448:LEPR protein, human; D020738:Leptin; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D054411:Receptors, Leptin; D005990:Glycerol