高脂膳食对肥胖易感和肥胖抵抗大鼠学习记忆能力的影响及机制

经过长期的高脂膳食后并非所有个体都会发生肥胖，还有些个体会产生肥胖抵抗现象。高脂膳食影响海马依赖的学习记忆等认知功能已被广泛证实，但目前关于高脂膳食对肥胖抵抗个体学习记忆能力影响的研究仍较少见。本文旨在对比研究高脂膳食对肥胖易感（obesity-prone, OP）和肥胖抵抗（obesity-resistant, OR）大鼠空间学习记忆能力的影响，并探讨其潜在的可能机制。Morris水迷宫结果显示，肥胖易感大鼠的学习能力显著低于对照大鼠和肥胖抵抗大鼠，但3组大鼠的记忆功能无显著性差异。Western印迹结果显示，与对照组相比，肥胖易感和肥胖抵抗大鼠海马内脑源性神经营养因子(BDNF)、血管内皮细胞生长因子(VEGF)和突触素(SYN)的含量均显著降低，丙二醛(MDA)和白介素1β(IL-1β)的含量均显著升高；且肥胖易感大鼠海马内上述蛋白质含量的变化更明显。免疫荧光染色和激光共聚焦显微镜扫描结果均显示，肥胖易感大鼠的海马神经发生水平显著低于肥胖抵抗大鼠和对照大鼠，但肥胖抵抗大鼠的海马神经发生水平与对照大鼠相比未见显著性变化。这些结果提示，高脂膳食可能是通过降低海马内突触可塑相关蛋白质的表达和神经发生，以及加剧炎症反应来损害肥胖易感大鼠的空间学习能力，而对肥胖抵抗大鼠的学习记忆能力影响不显著。

Effects of High-fat Diet on Learning and Memory in Obesity-prone and Obesity-resistant Rats and Underlying Mechanisms

It has been shown that some male Sprague-Dawle (SD) rats become obesity-prone (OP), while others become obesity-resistant (OR) under high fat diet (HFD) feeding. Moreover, HFD may impair hippocampal-dependent learning and memory. However, there are few, if any, reports about the effects of HFD on the learning and memory in obesity-resistant rats. This study aims to investigate the differences of learning and memory between obesity-prone and obesity-resistant rats, and to explore the possibly potential mechanisms. Morris water maze showed that the learning performance of obesity-prone rats significantly decreased when compared to control and obesity-resistant rats, but the memory had no significant differences among the three groups of rats. Western blot showed that obesity-prone and obesity-resistant rats had lower levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and synaptophysin (SYN), but both had increased levels of malondialdehyde (MDA) and interleukin 1β (IL-1β) compared to that of control rats. In addition, obesity-prone rats showed more significant changes in above proteins. Immunofluorescent staining and laser scanning confocal microscopy both showed that hippocampal neurogenesis significantly decreased in obesity-prone rats when compared to obesity-resistant and control rats, but there were no significant differences between obesity-resistant rats and control rats. These data suggest that HFD may impair the learning performance in obesity-prone rats through decreasing synaptic plasticity-related protein levels and hippocampal neurogenesis, and increasing neuronal inflammation, but HFD does not have obvious influence on obesity-resistant rats.