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Differential function of the α2A-adrenoceptor and phosphodiesterase-3B in human adipocytes of different origin

International Journal of Obesity volume 29, pages 1413–1421 (2005)Cite this article

Abstract

OBJECTIVE:

Human adipocytes can be obtained in vitro by differentiation of human preadipocytes or mesenchymal stem cells (hMSC). Although functionally similar to freshly isolated cells, no detailed comparison of the different cell types has been performed. The antilipolytic α2A-adrenoceptor (AR) and the cAMP-degrading enzyme Phosphodiesterase-3B (PDE3B) have been implicated in the fine-tuning of lipolysis but little is known regarding their role in human adipocytes nor whether their expression and/or function differs in fat cells from different precursors.

METHODS:

The effects of α2A-AR and PDE3B inhibition in mature adipocytes was determined and compared to that in differentiated preadipocytes and hMSC-derived fat cells. Gene expression was determined by real-time PCR and protein expression by Western blot.

RESULTS:

Noradrenaline (NA) stimulated lipolysis in preadipocytes and mature adipocytes but markedly reduced lipolysis in differentiated hMSC derived-adipocytes. This was due to a potent stimulation of α2A-AR since co-incubation with NA and the α2-AR-inhibitor yohimbine restored NA-induced lipolysis. The order of Yohimbine response was hMSC>preadipocytes>mature adipocytes. Although α2-AR mRNA expression was highest in mature adipocytes there was no difference in α2A-AR protein levels between the cell types. In contrast, Gαi2 mRNA and protein expression was significantly higher in MSC-derived adipocytes, suggesting that differences in the response to α2A-AR inhibition reside at the postreceptor level. Incubation with the cAMP-analog 8-bromo(8b) cAMP increased lipolysis in hMSC-derived fat cells while co-incubation with the PDE3-specific inhibitor OPC3911 did not alter the lipolytic effect. In contrast, OPC3911 increased 8bcAMP-induced lipolysis significantly in preadipocytes and mature adipocytes. The response to PDE3B inhibition was; mature adipocytes>preadipocytes>hMSC a finding that correlated significantly with both PDE3B mRNA expression and enzymatic activity.

CONCLUSION:

Although differentiated adipocytes of different origins display similar functional characteristics there are important differences in the regulation of lipolysis with a marked α2A-AR and less pronounced PDE3B effect in fat cells from MSCs.

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Acknowledgements

This work was supported by the foundations of Åke Wiberg, Tore Nilsson, Signe and Olof Wallenius, Magnus Bergvall, Åhlens and Novo Nordisk, the Swedish Medical Association, the Swedish Research Council, the Swedish Diabetes Association, the Tobias Foundation and the Swedish Cancer foundation.

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Authors and Affiliations

  1. Department of Medicine, Karolinska University Hospital, Stockholm, Sweden

    A Dicker, M Kaaman, V van Harmelen, G Åström & M Rydén

  2. Department of Laboratory Medicine, Division of Immunology Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

    K L Blanc

  3. Center for allogeneic stem cell transplantation, Karolinska University Hospital, Stockholm, Sweden

    K L Blanc

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  1. A Dicker
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  2. M Kaaman
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Correspondence to M Rydén.

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Dicker, A., Kaaman, M., van Harmelen, V. et al. Differential function of the α2A-adrenoceptor and phosphodiesterase-3B in human adipocytes of different origin. Int J Obes 29, 1413–1421 (2005). https://doi.org/10.1038/sj.ijo.0803042

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