Induction of the inflammasome protein cryopyrin (NLRP3) in visceral adipose tissue (VAT) promotes release of the pro-inflammatory cytokine interleukin-1β (IL1β) in obesity. While this mechanism contributes to peripheral metabolic dysfunction, effects on the brain remain unexplored. These studies investigated whether visceral adipose NLRP3 impairs cognition by activating microglial interleukin-1 receptor 1 (IL1R1). After observing protection against obesity-induced neuroinflammation and cognitive impairment in NLRP3KO mice, we transplanted VAT from obese WT or NLRP3KO donors into lean recipients. Transplantation of VAT from a WT donor (TRANSWT) increased hippocampal IL1β and impaired cognition, but VAT transplants from comparably obese NLRP3KO donors (TRANSKO) had no effect. Visceral adipose NLRP3 was required for deficits in long-term potentiation (LTP) in transplant recipients, and LTP impairment in TRANSWT mice was IL1-dependent. Flow cytometric and gene expression analyses revealed that VAT transplantation recapitulated the effects of obesity on microglial activation and IL1β gene expression, and visualization of hippocampal microglia revealed similar effects in vivo. Inducible ablation of IL1R1 in CX3CR1-expressing cells eliminated cognitive impairment in mice with dietary obesity and in transplant recipients and restored immunoquiescence in hippocampal microglia. These results indicate that visceral adipose NLRP3 impairs memory via IL1-mediated microglial activation, and suggest that NLRP3-IL1β signaling may underlie correlations between visceral adiposity and cognitive impairment in humans.

中文翻译：

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内脏脂肪NLRP3通过CX3CR1 +细胞上的IL-1R1损害肥胖症认知。

内脏脂肪组织（VAT）中炎性体蛋白冻融蛋白（NLRP3）的诱导促进肥胖中促炎性细胞因子白介素1β（IL1β）的释放。虽然这种机制导致周围的代谢功能障碍，但对大脑的影响仍待探索。这些研究调查了内脏脂肪NLRP3是否通过激活小胶质白细胞介素1受体1（IL1R1）损害认知。在观察到针对肥胖引起的NLRP3KO小鼠的神经炎症和认知障碍的保护后，我们将来自肥胖WT或NLRP3KO供体的VAT移植到瘦的接受者中。从野生型供体（TRANSWT）移植增值税会增加海马IL1β并损害认知，但从相对肥胖的NLRP3KO供体（TRANSKO）移植的增值税则没有效果。内脏脂肪NLRP3是移植受者长期增强（LTP）缺陷所必需的，而TRANSWT小鼠的LTP损伤是IL1依赖性的。流式细胞仪和基因表达分析表明，VAT移植概括了肥胖对小胶质细胞激活和IL1β基因表达的影响，而海马小胶质细胞的可视化显示了体内相似的作用。IL1R1在CX3CR1表达细胞中的诱导性消融消除了饮食性肥胖小鼠和移植受者的认知障碍，并恢复了海马小胶质细胞的免疫静止状态。这些结果表明，内脏脂肪NLRP3通过IL1介导的小胶质细胞活化来损害记忆，并暗示NLRP3-IL1β信号传导可能是人类内脏脂肪与认知障碍之间的相关性。