Uric Acid Produces an Inflammatory Response through Activation of NF-κB in the Hypothalamus: Implications for the Pathogenesis of Metabolic Disorders.
Uric Acid Produces an Inflammatory Response through Activation of NF-κB in the Hypothalamus: Implications for the Pathogenesis of Metabolic Disorders.
复制标题
DOI：
10.1038/srep12144
复制
发表时间：
2015-07-16
影响因子：
4.6
通讯作者：
Cen X
中科院分区：
文献类型：
--
作者：
Lu W;Xu Y;Shao X;Gao F;Li Y;Hu J;Zuo Z;Shao X;Zhou L;Zhao Y;Cen X
流行病学研究表明，尿酸（UA）水平升高可预测代谢综合征和糖尿病的发生；然而，目前尚无直接证据，其潜在机制也仍不明确。在此，我们发现高尿酸饮食会触发促炎细胞因子的表达，激活核因子-κB（NF-κB）通路，并加剧下丘脑的神经胶质增生。脑室内注射尿酸会诱发下丘脑炎症和反应性神经胶质增生，而抑制NF-κB可显著改善这些影响。此外，磁共振成像证实，啮齿动物和人类的高尿酸血症与下丘脑内侧基底部的神经胶质增生有关。重要的是，给予尿酸的大鼠出现血脂异常和葡萄糖不耐受，这可能是由下丘脑炎症和下丘脑神经内分泌改变介导的。这些结果表明，尿酸可通过NF-κB信号通路引发下丘脑炎症。我们的研究结果为尿酸诱导的代谢紊乱提供了一种潜在的治疗策略。
Epidemiological studies have shown that an elevated uric acid (UA) level predicts the development of metabolic syndrome and diabetes; however, there is no direct evidence of this, and the underlying mechanism remains unclear. Here, we showed that a high-UA diet triggered the expression of pro-inflammatory cytokines, activated the NF-κB pathway, and increased gliosis in the hypothalamus. Intracerebroventricular injection of UA induced hypothalamic inflammation and reactive gliosis, whereas these effects were markedly ameliorated by the inhibition of NF-κB. Moreover, magnetic resonance imaging confirmed that hyperuricemia in rodents and humans was associated with gliosis in the mediobasal hypothalamus. Importantly, the rats administered UA exhibited dyslipidemia and glucose intolerance, which were probably mediated by hypothalamic inflammation and hypothalamic neuroendocrine alterations. These results suggest that UA can cause hypothalamic inflammation via NF-κB signaling. Our findings provide a potential therapeutic strategy for UA-induced metabolic disorders.