Both hyperuricemia and adipose tissue renin-angiotensin system (RAS) are closely associated with multiple metabolic and cardiovascular diseases. We previously reported that uric acid could upregulate tissue RAS in adipocytes. In the present study, we aimed to reveal the involvement of toll-like receptors (TLRs) in uric acid-induced RAS activation in adipose tissue. A hyperuricemia rat model fed with a high-fructose diet and rat primary adipocytes were used in this study. Here, we inhibited TLR2 and TLR4 expression in adipose tissue and cultured adipocytes using small interfering RNA (siRNA). We found that high fructose-fed rats had hyperuricemia, higher body weight and greater adipose tissue content. We also found that hyperuricemia rats had raising blood pressure, higher expression levels of inflammatory cytokines and RAS components in adipose tissue, which could be prevented by TLR2/4-siRNA infection. In vitro study, uric acid caused a dose- and time-dependent increase in the mRNA expression of TLR2 and TLR4 in rat adipocytes. Uric acid could increase inflammatory cytokines and upregulate tissue RAS in rat adipocytes, which were both blocked with TLR2/4-siRNA infection. TNF-α and IL-6 could also result in an activation of tissue RAS expression in adipocytes. In conclusion, TLR2/4 mediated adipose inflammation plays a key role in RAS activation induced by uric acid in adipose tissue.

中文翻译：

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TLR2和TLR4介导由尿酸诱导的脂肪组织肾素-血管紧张素系统的激活。

高尿酸血症和脂肪组织肾素-血管紧张素系统（RAS）与多种代谢性疾病和心血管疾病密切相关。我们先前曾报道尿酸可以上调脂肪细胞中的组织RAS。在本研究中，我们旨在揭示toll样受体（TLR）与尿酸诱导的脂肪组织中的RAS活化有关。本研究使用高果糖饮食喂养的高尿酸血症大鼠模型和大鼠原代脂肪细胞。在这里，我们使用小的干扰RNA（siRNA）抑制了脂肪组织和培养的脂肪细胞中TLR2和TLR4的表达。我们发现，高果糖喂养的大鼠患有高尿酸血症，较高的体重和较高的脂肪组织含量。我们还发现高尿酸血症大鼠血压升高，TLR2 / 4-siRNA感染可以预防脂肪组织中炎性细胞因子和RAS成分的高表达水平。在体外研究中，尿酸引起大鼠脂肪细胞中TLR2和TLR4 mRNA表达的剂量和时间依赖性增加。尿酸可以增加大鼠脂肪细胞中的炎性细胞因子并上调组织RAS，而后者均被TLR2 / 4-siRNA感染所阻断。TNF-α和IL-6也可能导致脂肪细胞中组织RAS表达的激活。总之，TLR2 / 4介导的脂肪炎症在脂肪组织中尿酸诱导的RAS活化中起关键作用。尿酸可以增加大鼠脂肪细胞中的炎性细胞因子并上调组织RAS，而后者均被TLR2 / 4-siRNA感染所阻断。TNF-α和IL-6也可能导致脂肪细胞中组织RAS表达的激活。总之，TLR2 / 4介导的脂肪炎症在脂肪组织中尿酸诱导的RAS活化中起关键作用。尿酸可以增加大鼠脂肪细胞中的炎性细胞因子并上调组织RAS，而后者均被TLR2 / 4-siRNA感染所阻断。TNF-α和IL-6也可能导致脂肪细胞中组织RAS表达的激活。总之，TLR2 / 4介导的脂肪炎症在脂肪组织中尿酸诱导的RAS活化中起关键作用。