Dopamine D2 receptor upregulates leptin and IL-6 in adipocytes

Leptin is a pro-inflammatory cytokine secreted by the adipose tissue. Dopamine D 2 receptors (D 2 Rs) have anti-inflammatory effects in the brain and kidney tissues. Mouse and human adipocytes express D 2 R; D 2 R protein was 10-fold greater in adipocytes from human visceral tissue than subcutaneous tissue. However, the function of D 2 R in adipocytes is not well understood. 3T3-L1 cells were treated with D 2 -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 D 2 R antagonist L741,626. Similarly, siRNA-mediated silencing of Drd2 decreased the leptin, IL-6, mRNA, and protein expressions. The D 2 R-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 D 2 R on leptin in vivo. Our results suggest that the stimulation of D 2 R increases leptin production and may have a tissue-specific pro-inflammatory effect in adipocytes.