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Background: The aim of the present study was to investigate whether histamine induces up-regulated expression of uncoupling protein 2 (UCP2) and fat acid-binding protein (aP2) in white adipocytes (differentiated 3T3-L1 cells). Methods: Differentiation of 3T3-L1 preadipocytes to adipocytes was induced by the addition of 5 μg/mL insulin, 1 μmol/L dexamethasone, 10 mmol/L 1-isobutyl-3-methylxanthine, 1% dimethylsulfoxide, and 10% fetal bovine serum in Dulbecco's modification of Eagle's medium. Total RNA from differentiated 3T3-L1 cells was extracted and semi-quantitative RT-PCR was performed to determine the levels of UCP2 and aP2 mRNA. The expression level of UCP2 protein was determined by Western blot analysis. Results: Histamine at a concentration of 30 μmol/L significantly increased the expression of UCP2 mRNA and UCP2 protein, and expression levels reached a peak value. There were significant differences in the expression levels of UCP2 mRNA and UCP2 protein in adipocytes treated with 30 μmol/L histamine at various time points within 48 h, and their levels reached a peak value after 6 h of incubation. In addition, histamine increased the expression level of aP2 mRNA in adipocytes. Expression of aP2 mRNA in adipocytes reached the highest value at a concentration of 20 μmol/L histamine after 6-h incubation. Finally, we found that diphenhydramine (a H1 receptor antagonist) significantly decreased expression levels of UCP2 mRNA and protein, as well as aP2 mRNA. There were significant differences in expression levels of UCP2 and aP2 mRNA in adipocytes treated at concentrations of 20 μmol/L histamine and diphenhydramine, respectively. Conclusions: These data reveal that histamine up-regulated the expression of UCP2 and aP2 in vitro in white adipocytes. Clin Chem Lab Med 2007;45:1199–206. [ABSTRACT FROM AUTHOR]