Effect of zinc-alpha2-glycoprotein (ZAG) on expression of uncoupling proteins in skeletal muscle and adipose tissue

Cancer Letters
Paul Sanders, M J Tisdale

Abstract

The plasma protein zinc-alpha2-glycoprotein (ZAG) has been shown to be identical with a lipid mobilizing factor capable of inducing loss of adipose tissue in cancer cachexia through an increased lipid mobilization and utilization. The ability of ZAG to induce uncoupling protein (UCP) expression has been determined using in vitro models of adipose tissue and skeletal muscle. ZAG induced a concentration-dependent increase in the expression of UCP-1 in primary cultures of brown, but not white, adipose tissue, and this effect was attenuated by the beta3-adrenergic receptor (beta3-AR) antagonist SR59230A. A 6.5-fold increase in UCP-1 expression was found in brown adipose tissue after incubation with 0.58 microM ZAG. ZAG also increased UCP-2 expression 3.5-fold in C2C12 murine myotubes, and this effect was also attenuated by SR59230A and potentiated by isobutylmethylxanthine, suggesting a cyclic AMP-mediated process through interaction with a beta3-AR. ZAG also produced a dose-dependent increase in UCP-3 in murine myotubes with a 2.5-fold increase at 0.58 microM ZAG. This effect was not mediated through the beta3-AR, but instead appeared to require mitogen activated protein kinase. These results confirm the ability of ZAG to directly...Continue Reading

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Citations

Jun 2, 2010·International Journal of Obesity : Journal of the International Association for the Study of Obesity·C BingP Trayhurn
Aug 11, 2010·International Journal of Obesity : Journal of the International Association for the Study of Obesity·S T Russell, M J Tisdale
Sep 22, 2010·International Journal of Obesity : Journal of the International Association for the Study of Obesity·S T Russell, M J Tisdale
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Feb 21, 2013·Clinica Chimica Acta; International Journal of Clinical Chemistry·Viviane de Oliveira Leal, Denise Mafra
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