Several studies suggest a role of extracellular adenine nucleotides in regulating adipose tissue functions via the purinergic signaling network. Metabolic studies in mice with global deletion of the purinergic receptor P2X7 on the C57BL/6 background indicate that this receptor has only a minor role in adipose tissue for diet-induced inflammation or cold-triggered thermogenesis. However, recent data show that a polymorphism (P451L) present in C57BL/6 mice attenuates P2X7 receptor function, whereas BALB/c mice express the fully functional P451 allele. To determine the potential role of P2rx7 under metabolic and thermogenic stress conditions, we performed comparative studies using male P2rx7 knockout (KO) and respective wild-type controls on both BALB/c and C57BL/6 backgrounds. Our data show that adipose P2rx7 mRNA levels are increased in obese mice. Moreover, P2rx7 deficiency results in reduced levels of circulating CCL2 and IL6 with a moderate effect on gene expression of pro-inflammatory markers in white adipose tissue and liver of BALB/c and C57BL/6 mice. However, P2X7 expression does not alter body weight, insulin resistance, and hyperglycemia associated with high-fat diet feeding on both genetic backgrounds. Furthermore, deficiency of P2rx7 is dispensable for energy expenditure at thermoneutral and acute cold exposure conditions. In summary, these data show that—apart from a moderate effect on inflammatory cytokines—P2X7 plays only a minor role in inflammatory and thermogenic effects of white and brown adipose tissue even on the BALB/c background.

几项研究表明细胞外腺嘌呤核苷酸在通过嘌呤能信号网络调节脂肪组织功能中发挥作用。对 C57BL/6 背景上嘌呤能受体 P2X7 整体缺失的小鼠进行的代谢研究表明，该受体在脂肪组织中对饮食诱导的炎症或冷触发的产热作用很小。然而，最近的数据显示 C57BL/6 小鼠中存在的多态性 (P451L) 减弱了 P2X7 受体功能，而 BALB/c 小鼠表达了全功能的 P451 等位基因。为了确定P2rx7在代谢和产热应激条件下的潜在作用，我们使用雄性P2rx7进行了比较研究BALB/c 和 C57BL/6 背景下的敲除 (KO) 和各自的野生型对照。我们的数据显示肥胖小鼠的脂肪P2rx7 mRNA 水平增加。此外，P2rx7缺乏导致循环 CCL2 和 IL6 水平降低，对 BALB/c 和 C57BL/6 小鼠的白色脂肪组织和肝脏中促炎标志物的基因表达有中等影响。然而，在两种遗传背景下，P2X7 表达不会改变与高脂肪饮食相关的体重、胰岛素抵抗和高血糖。此外，P2rx7 的缺乏对于热中性和急性寒冷暴露条件下的能量消耗是可有可无的。总之，这些数据表明，除了对炎性细胞因子的适度影响外，即使在 BALB/c 背景下，P2X7 在白色和棕色脂肪组织的炎症和产热效应中也仅起次要作用。