Short-term (3-day) consumption of a high fat diet (HFD) rich in saturated fats is associated with a neuroinflammatory response and subsequent cognitive impairment in aged, but not young adult, male rats. This exaggerated effect in aged rats could be due to a "primed" microglial phenotype observed in the normal aging process in rodents in which aged microglia display a potentiated response to immune challenge. Here, we investigated the impact of HFD on microglial priming and lipid composition in the hippocampus and amygdala of young and aged rats. Furthermore, we investigated the microglial response to palmitate, the main saturated fatty acid (SFA) found in HFD that is proinflammatory. Our results indicate that HFD increased gene expression of microglial markers of activation indicative of microglial priming, including CD11b, MHCII, CX3CR1, and NLRP3, as well as the pro-inflammatory marker IL-1β in both hippocampus and amygdala-derived microglia. Furthermore, HFD increased the concentration of SFAs and decreased the concentration of polyunsaturated fatty acids (PUFAs) in the hippocampus. We also observed a specific decrease in the anti-inflammatory PUFA docosahexaenoic acid (DHA) in the hippocampus and amygdala of aged rats. In a separate cohort of young and aged animals, isolated microglia from the hippocampus and amygdala exposed to palmitate in vitro induced an inflammatory gene expression profile mimicking the effects of HFD in vivo. These data suggest that palmitate may be a critical nutritional signal from the HFD that is directly involved in hippocampal and amygdalar inflammation. Interestingly, microglial activation markers were increased in response to HFD or palmitate in an age-independent manner, suggesting that HFD sensitivity of microglia, under these experimental conditions, is not the sole mediator of the exaggerated inflammatory response observed in whole tissue extracts from aged HFD-fed rats.

中文翻译：

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成人和老年海马和杏仁核中的脂肪食物、脂肪酸和小胶质细胞启动

短期（3 天）食用富含饱和脂肪的高脂肪饮食 (HFD) 与老年雄性大鼠（而非年轻成年雄性大鼠）的神经炎症反应和随后的认知障碍有关。这种对老年大鼠的夸大作用可能是由于在啮齿类动物的正常衰老过程中观察到的“引发”小胶质细胞表型，其中老年小胶质细胞对免疫挑战表现出增强的反应。在这里，我们研究了 HFD 对年轻和老年大鼠海马和杏仁核中小胶质细胞启动和脂质组成的影响。此外，我们研究了小胶质细胞对棕榈酸酯的反应，棕榈酸酯是 HFD 中发现的促炎性的主要饱和脂肪酸 (SFA)。我们的结果表明，HFD 增加了指示小胶质细胞启动的小胶质细胞激活标志物的基因表达，包括 CD11b、MHCII、CX3CR1 和 NLRP3，以及海马和杏仁核衍生的小胶质细胞中的促炎标志物 IL-1β。此外，HFD 增加了海马中 SFA 的浓度并降低了多不饱和脂肪酸 (PUFA) 的浓度。我们还观察到老年大鼠海马和杏仁核中抗炎 PUFA 二十二碳六烯酸 (DHA) 的特定减少。在一组不同的年轻和老年动物中，从海马体和杏仁核中分离出的小胶质细胞在体外暴露于棕榈酸酯，诱导炎症基因表达谱，模拟体内 HFD 的影响。这些数据表明，棕榈酸酯可能是来自 HFD 的关键营养信号，直接参与海马和杏仁核炎症。有趣的是，