Dopamine D2 receptor upregulates leptin and IL-6 in adipocytes.

Leptin is a pro-inflammatory cytokine secreted by the adipose tissue. Dopamine D receptors (DRs) have anti-inflammatory effects in the brain and kidney tissues. Mouse and human adipocytes express DR; DR protein was 10-fold greater in adipocytes from human visceral tissue than subcutaneous tissue. However, the function of DR in adipocytes is not well understood. 3T3-L1 cells were treated with D-like receptor agonist quinpirole, and immunoblot and quantitative PCR were performed. Quinpirole increased the protein and mRNA expression of leptin and IL-6, but not adiponectin and visfatin (24 h). It also increased the mRNA expression of TNF-α , MCP1, and NFkB-p50. An acute increase in the protein expression of leptin and TNF-α was also found in the cells treated with quinpirole. The leptin concentration in the culture media was increased by quinpirole-bathing the 3T3-L1 adipocytes. These quinpirole effects on leptin and IL-6 expression were prevented by the DR antagonist L741,626. Similarly, siRNA-mediated silencing of decreased the leptin, IL-6, mRNA, and protein expressions. The DR-mediated increase in leptin expression was prevented by the phosphoinositide 3-kinase inhibitor LY294002. Acute quinpirole treatment in C57Bl/6J mice increased serum leptin concentration and leptin mRNA in visceral adipocyte tissue but not in subcutaneous adipocytes, confirming the stimulatory effect of DR on leptin in vivo. Our results suggest that the stimulation of DR increases leptin production and may have a tissue-specific pro-inflammatory effect in adipocytes.