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Background: Studies have revealed an association between overweight/obesity and multiple myeloma. However, the factors linking a dysregulated energy metabolism to this disease have not been identified. Adipose tissue produces and secretes the adipokines leptin, adiponectin and resistin, involved in metabolism and cell growth. Methods: We measured the plasma concentrations of these three adipokines in newly diagnosed multiple myeloma as well as in patients with relapse. We further explored the importance of leptin in multiple myeloma by performing gene expression profiling in two myeloma cell lines. Results: At diagnosis, leptin was increased ( P < 0.05) in both female and male patients compared with controls. Adiponectin was reduced ( P < 0.05) among male patients, whereas no significant changes in resistin were noted among any patients. In patients with relapse and treated with thalidomide, no particular adipokine pattern was revealed. Leptin induced the expression of several genes important for cell signaling, growth and viability. Conclusions: The plasma concentrations of leptin and adiponectin, but not resistin, were abnormal in newly diagnosed multiple myeloma. Adipose tissue may modify the growth and metabolism of myeloma cells through adipokine-mediated effects. [ABSTRACT FROM AUTHOR]