Dopamine D2 receptor upregulates leptin and IL-6 in adipocytes

Xiaoyan Wang,Van Anthony Villar,Andrew Tiu,Kiran K Upadhyay,Santiago Cuevas

doi:10.1194/jlr.m081000

Abstract

Leptin is a pro-inflammatory cytokine secreted by the adipose tissue. Dopamine D2 receptors (D2Rs) have anti-inflammatory effects in the brain and kidney tissues. Mouse and human adipocytes express D2R; D2R protein was 10-fold greater in adipocytes from human visceral tissue than subcutaneous tissue. However, the function of D2R in adipocytes is not well understood. 3T3-L1 cells were treated with D2-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 D2R antagonist L741,626. Similarly, siRNA-mediated silencing of Drd2 decreased the leptin, IL-6, mRNA, and protein expressions. The D2R-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 D2R on leptin in vivo. Our results suggest that the stimulation of D2R increases leptin production and may have a tissue-specific pro-inflammatory effect in adipocytes.

Highlights

Leptin is a pro-inflammatory cytokine secreted by the adipose tissue
To compare the relative abundance of D2 receptor (D2R) in visceral and subcutaneous adipocytes, primary cultures of human adipocytes from subcutaneous and visceral fat were studied. qRt-PCR analyses showed that D2R mRNA was 10-fold greater in visceral than subcutaneous adipocytes (Fig. 1C)
These data show that D2R upregulates the protein expression of adipokines, mainly leptin, IL-6, and possibly TNF, in 3T3-L1 cells by increasing their mRNA expression

Summary

Introduction

Leptin is a pro-inflammatory cytokine secreted by the adipose tissue. Dopamine D2 receptors (D2Rs) have antiinflammatory effects in the brain and kidney tissues. Quinpirole increased the protein and mRNA expression of leptin and IL-6, but not adiponectin and visfatin (24 h). An acute increase in the protein expression of leptin and TNF-a was found in the cells treated with quinpirole. Our results suggest that the stimulation of D2R increases leptin production and may have a tissue-specific pro-inflammatory effect in adipocytes.—Wang, X., V. Adipose tissue is involved in the storage and mobilization of lipids and acts as an endocrine organ by producing numerous cytokines, such as pro-inflammatory molecules These pro-inflammatory molecules include interleukin (IL)-6, TNF- , and adipokines such as leptin [1]. Mouse and human adipocytes express dopamine receptors but their effects on inflammation are controversial. We tested the hypothesis that the Abbreviations: AKT, protein kinase B; D2R, dopamine D2 receptor; IL, interleukin; OB-R, leptin receptor; 1 To whom correspondence should

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Conclusion