Visfatin expression is hormonally regulated by metabolic and sex hormones in 3T3-L1 pre-adipocytes and adipocytes

Aim: The novel adipokine visfatin has 'insulin-mimicking' effects and is increased in models of diet-induced obesity, but factors that regulate visfatin have not been fully elucidated. Methods In order to determine visfatin regulation in adipocyte development and metabolism, as well as in pathophysiological conditions related to metabolic syndrome, endogenous visfatin expression was measured in 3T3-L1 pre-adipocytes and adipocytes using real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR). Results: A marked increase in visfatin expression was observed during differentiation, with a 2.2-fold increase between preconfluent and 2-day confluent cells even before differentiation was initiated. A further 4.1-fold increase was induced from day 0 to day 9 of differentiation (overall ninefold). Overnight incubation with dexamethasone (10(-8) to 10(-2) M) increased visfatin expression in both pre-adipocytes (1.5- to 3.3-fold, p < 0.05) and adipocytes (1.9-fold, p < 0.01). All other treatments decreased visfatin expression. In pre-adipocytes, visfatin expression decreased by 23% at a concentration of 1 mu M insulin, 15% at 1-15 nM T3, 15% at 10 nM-1 mu M progesterone, 33-44% at 10 nM-1 mu M testosterone, 50% with palmitate and 30% with oleate (p < 0.05 for all). In adipocytes, insulin had a much greater effect, decreasing visfatin by 77% at 100 nM (p < 0.01), whereas oleate and sex hormones did not affect visfatin expression. However, tumor necrosis factor alpha, which had no effect on pre-adipocytes, significantly decreased visfatin in adipocytes by 26% at 10 ng/ml (p < 0.05). Interestingly, the thiazolidinedione (TZD) rosiglitizone also decreased visfatin by 28% at a concentration of 1 mu M (p < 0.01). Conclusion: In summary, while the mechanism of visfatin action remains to be elucidated, the clear effects of multiple hormones on visfatin expression support a physiological role.