Contribution of extracellular ATP on the cell-surface F₁F₀-ATP synthase-mediated intracellular triacylglycerol accumulation

Abstract

Cell-surface F₁F₀-ATP synthase was involved in the cell signaling mediating various biological functions. Recently, we found that cell-surface F₁F₀-ATP synthase plays a role on intracellular triacylglycerol accumulation in adipocytes, and yet, the underlying mechanisms remained largely unknown. In this study, we investigated the role of extracellular ATP on the intracellular triacylglycerol accumulation. We demonstrated that significant amounts of ATP were produced extracellularly by cultured 3T3-L1 adipocytes and that the antibodies against α and β subunits of F₁F₀-ATP synthase inhibited the extracellular ATP production. Piceatannol, a F₁F₀-ATP synthase inhibitor, and apyrase, an enzyme which degrades extracellular ATP, suppressed triacylglycerol accumulation. The selective P2Y₁ receptor antagonist MRS2500 significantly inhibited triacylglycerol accumulation, whereas the selective P2X receptor antagonist NF279 has less effect. The present results indicate that cell-surface F₁F₀-ATP synthase on adipocytes is functional in extracellular ATP production and that the extracellular ATP produced contributes, at least in part, to the cell-surface F₁F₀-ATP synthase-mediated intracellular triacylglycerol accumulation in adipocytes through P2Y₁ receptor.