Glucocorticoids Mediate Short-Term High-Fat Diet Induction of Neuroinflammatory Priming, the NLRP3 Inflammasome, and the Danger Signal HMGB1.
Glucocorticoids Mediate Short-Term High-Fat Diet Induction of Neuroinflammatory Priming, the NLRP3 Inflammasome, and the Danger Signal HMGB1.
复制标题
糖皮质激素介导了神经炎性启动，NLRP3炎性体和危险信号HMGB1的短期高脂饮食诱导。
DOI：
10.1523/eneuro.0113-16.2016
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发表时间：
2016-07
期刊：
影响因子：
3.4
通讯作者：
Barrientos RM
中科院分区：
文献类型：
--
作者：
Sobesky JL;D'Angelo HM;Weber MD;Anderson ND;Frank MG;Watkins LR;Maier SF;Barrientos RM
我们吃的食物对新陈代谢和心脏生理学的影响已经研究了几十年，但对食物对CNS的影响或这些影响可能导致的行为表现知之甚少。先前的研究表明，长期食用高脂肪食物导致饮食诱导的肥胖会使大脑对随后的挑战性刺激的炎症反应敏感，从而导致长期记忆形成的缺陷。本文报道的新发现表明，短期食用高脂肪饮食（HFD）会产生相同的结果，因此可以在肥胖和相关合并症发生之前很久就检查参与这一过程的机制。喂食HFD 3 d的大鼠表现出海马中皮质酮、炎性小体相关蛋白NLRP 3（HFD样受体蛋白3）和内源性危险信号HMGB 1（高迁移率族蛋白1）的增加。低剂量（10 μg/kg）脂多糖（LPS）免疫激发增强了喂食HFD的大鼠海马中的神经炎症反应，并导致长期记忆形成缺陷，在喂食常规食物的大鼠中未观察到这种效应。用糖皮质激素受体拮抗剂米非司酮阻断皮质酮的作用可防止未受攻击动物的NLRP 3和HMG B1增加，使对LPS的促炎反应正常化，并防止记忆障碍。这些数据表明，短期HFD消费增加的脆弱性，由免疫挑战引起的记忆中断上调重要的神经炎症启动和危险信号在海马，这些影响是由海马皮质酮的增加介导的。
The impact of the foods we eat on metabolism and cardiac physiology has been studied for decades, yet less is known about the effects of foods on the CNS, or the behavioral manifestations that may result from these effects. Previous studies have shown that long-term consumption of high-fat foods leading to diet-induced obesity sensitizes the inflammatory response of the brain to subsequent challenging stimuli, causing deficits in the formation of long-term memories. The new findings reported here demonstrate that short-term consumption of a high-fat diet (HFD) produces the same outcomes, thus allowing the examination of mechanisms involved in this process long before obesity and associated comorbidities occur. Rats fed an HFD for 3 d exhibited increases in corticosterone, the inflammasome-associated protein NLRP3 (nod-like receptor protein 3), and the endogenous danger signal HMGB1 (high-mobility group box 1) in the hippocampus. A low-dose (10 μg/kg) lipopolysaccharide (LPS) immune challenge potentiated the neuroinflammatory response in the hippocampus of rats fed the HFD, and caused a deficit in the formation of long-term memory, effects not observed in rats fed regular chow. The blockade of corticosterone action with the glucocorticoid receptor antagonist mifepristone prevented the NLRP3 and HMGB1 increases in unchallenged animals, normalized the proinflammatory response to LPS, and prevented the memory impairment. These data suggest that short-term HFD consumption increases vulnerability to memory disruptions caused by an immune challenge by upregulating important neuroinflammatory priming and danger signals in the hippocampus, and that these effects are mediated by increases in hippocampal corticosterone.