Introduction

Diminished brain insulin sensitivity is associated with reduced cognitive function. Docosahexaenoic acid (DHA) is known to maintain normal brain function.

Objectives

This study aimed to determine whether DHA impacts hippocampal insulin sensitivity and cognitive function in aged rats fed a high-fat diet (HFD).

Methods

Eight-month-old female Sprague-Dawley rats were randomly divided into three groups (n = 50 each). Rats in the aged group, HFD group, and DHA treatment group received standard diet (10 kcal% fat), HFD (45 kcal% fat), and DHA-enriched HFD (45 kcal% fat, 1% DHA, W/W) for 10 months, respectively. Four-month-old female rats (n = 40) that received a standard diet served as young controls. Neuroinflammation, oxidative stress, amyloid formation, and tau phosphorylation in the hippocampus, as well as systemic glucose homeostasis and cognitive function, were tested.

Results

DHA treatment relieved a block in the insulin signaling pathway and consequently protected aged rats against HFD-induced hippocampal insulin resistance. The beneficial effects were explained by a DHA-induced decrease in systemic glucose homeostasis dysregulation, hippocampal neuroinflammation and oxidative stress. In addition, DHA treatment broke the reciprocal cycle of hippocampal insulin resistance, Aβ burden, and tau hyperphosphorylation. Importantly, treatment of model rats with DHA significantly increased their cognitive capacity, as evidenced by their increased hippocampal-dependent learning and memory, restored neuron morphology, enhanced cholinergic activity, and activated cyclic AMP-response element-binding protein.

Conclusion

DHA improves cognitive function by enhancing hippocampal insulin sensitivity.

中文翻译：

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二十二碳六烯酸增强海马胰岛素敏感性促进高脂饮食老年大鼠的认知功能

介绍

脑胰岛素敏感性降低与认知功能降低有关。众所周知，二十二碳六烯酸 (DHA) 可以维持正常的大脑功能。

目标

本研究旨在确定 DHA 是否影响喂食高脂肪饮食 (HFD) 的老年大鼠的海马胰岛素敏感性和认知功能。

方法

八个月大的雌性 Sprague-Dawley 大鼠被随机分为三组（每组 n = 50）。老年组、HFD 组和 DHA 治疗组的大鼠接受标准饮食（10 kcal% 脂肪）、HFD（45 kcal% 脂肪）和富含 DHA 的 HFD（45 kcal% 脂肪，1% DHA，W/W）分别为 10 个月。接受标准饮食的四个月大的雌性大鼠 (n = 40) 作为年轻的对照。测试了海马体中的神经炎症、氧化应激、淀粉样蛋白形成和 tau 蛋白磷酸化，以及全身葡萄糖稳态和认知功能。

结果

DHA 治疗解除了胰岛素信号通路的阻滞，从而保护老年大鼠免受 HFD 诱导的海马胰岛素抵抗。有益效果可以通过 DHA 诱导的全身葡萄糖稳态失调、海马神经炎症和氧化应激减少来解释。此外，DHA 治疗打破了海马胰岛素抵抗、Aβ 负荷和 tau 过度磷酸化的相互循环。重要的是，用 DHA 治疗模型大鼠显着提高了它们的认知能力，这可以从它们海马依赖性学习和记忆的增加、神经元形态的恢复、胆碱能活性的增强以及环 AMP 反应元件结合蛋白的激活中得到证明。

结论

DHA 通过增强海马胰岛素敏感性来改善认知功能。