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Acta Physiologica 2012; Volume 206, Supplement 693
Joint FEPS and Spanish Physiological Society Scientific Congress 2012
9/8/2012-9/11/2012
Santiago de Compostela, Spain
DOPAMINE D2 RECEPTORS REGULATE LEPTIN IN ADIPOCYTES.
Abstract number: O216
Cuevas1 S, Yang1 Y, Zhang1 Y, Armando1 I, Jose1 P
1Medicine, University of Maryland
Objectives:
Leptin, secreted by adipose tissue which regulates food intake and energy homeostasis, is a pro-inflammatory cytokine that also regulates the production of other pro-inflammatory factors. Mouse and human adipocytes express dopamine D2 receptors (D2R). We tested the hypothesis that the D2R regulates the expression of leptin and other adipokines/cytokines in adipocytes.
Materials:
Mouse 3T3-L1 cells were differentiated to adipocytes for 3 days, and studied 8 days after differentiation.
Results:
Stimulation of the D2R with quinpirole (1mM, 24h) had no effect on adiponectin and visfatin but increased IL-6 (49±7%, P<0.05, western blot) and leptin (23±8%, P<0.05; western blot) in adipocytes and in the media (78±19%, P<0.05, ELISA). D2R stimulation also increased leptin (1.50±0.03 fold, P<0.05), IL-6 (2.44±0.08 fold, P<0.05), and TNF alpha; (2.23±0.06 fold, P<0.05) gene expression (qRT-PCR). These effects were prevented by a D2R selective antagonist (L741,626, 1mM, 24h). Conversely silencing D2R expression with siRNA decreased the protein (51.7±9.6%, P<0.05; western blot) and gene expression of leptin (0.38±0.01 fold, P<0.05) in adipocytes, decreased leptin in the media (26.2±3.9% pg/mg protein, P<0.05, ELISA), and decreased IL-6 (0.58±0.01-fold, P<0.05) and TNF alpha;; (0.86±0.02-fold, P<0.05) mRNA. The D2R-mediated increase in leptin was prevented by a PI3K inhibitor (LY294002, 10mM, 24hM, 24h), suggesting that the D2R regulates leptin through the PI3K-Akt pathway. The effect of the D2R agonist was blunted in adipocytes cultured in insulin-free media but was restored by the addition of insulin (1mg/ml, 24h).
Conclusions:
Our results suggest that the D2R may play a significant role in the regulation of the expression of leptin and IL-6 in adipocytes in the presence of insulin and may affect the role adipose tissue in energy homeostasis.
To cite this abstract, please use the following information:
Acta Physiologica 2012; Volume 206, Supplement 693 :O216