Sex Differences in High-fat Diet-induced Obesity, Metabolic Alterations and Learning, and Synaptic Plasticity Deficits in Mice
Sex Differences in High-fat Diet-induced Obesity, Metabolic Alterations and Learning, and Synaptic Plasticity Deficits in Mice
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DOI：
10.1038/oby.2009.273
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发表时间：
2010-03-01
期刊：
影响因子：
6.9
通讯作者：
Chiou, Lih-Chu
中科院分区：
文献类型：
--
作者：
Hwang, Ling-Ling;Wang, Chien-Hua;Chiou, Lih-Chu
肥胖是老年人认知功能障碍的潜在危险因素。利用高脂饮食（HFD）诱导的肥胖小鼠模型，我们研究了HFD对肥胖、代谢和应激激素、学习能力和海马突触可塑性的影响。喂食HFD（3周至9-12个月）的雄性和雌性C57 BL/6 J小鼠的体重均显著高于性别特异性对照组。与肥胖的雌性小鼠相比，肥胖的雄性小鼠的能量摄入量相似，但体重增加更多。肥胖雄性小鼠出现高血糖症、高胰岛素血症、高胆固醇血症和高瘦素血症，但不出现高甘油三酯血症。肥胖女性的高胰岛素血症和高胆固醇血症较肥胖男性少，无高血糖和高甘油三酯血症。在情境恐惧条件反射和跳台被动回避任务中，肥胖雄性小鼠的学习成绩比正常对照组差，而雌性小鼠没有。这些学习缺陷不是由于感觉运动障碍所验证的开放领域和热板测试。虽然基础突触传递特性正常组和HFD组之间的突触可塑性（输入输出传递和成对脉冲易化（PPF）比率）没有显著差异，（长时程增强（LTP）和长时程抑制（LTD））在分离自肥胖雄性而非雌性小鼠的海马切片的Schaffer侧支-CA 1突触处较低，与其性别特异性对照相比。我们的研究结果表明，雄性小鼠比雌性小鼠更容易受到HFD对体重增加、代谢改变和学习缺陷以及海马突触可塑性的影响。
Obesity is a potential risk factor for cognitive deficits in the elder humans. Using a high-fat diet (HFD)-induced obese mouse model, we investigated the impacts of HFD on obesity, metabolic and stress hormones, learning performance, and hippocampal synaptic plasticity. Both male and female C57BL/6J mice fed with HFD (3 weeks to 9-12 months) gained significantly more weights than the sex-specific control groups. Compared with the obese female mice, the obese males had similar energy intake but developed more weight gains. The obese male mice developed hyperglycemia, hyperinsulinemia, hypercholesterolemia, and hyperleptinemia, but not hypertriglyceridemia. The obese females had less hyperinsulinemia and hypercholesterolemia than the obese males, and no hyperglycemia and hypertriglyceridemia. In the contextual fear conditioning and step-down passive avoidance tasks, the obese male, but not female, mice showed poorer learning performance than their normal counterparts. These learning deficits were not due to sensorimotor impairment as verified by the open-field and hot-plate tests. Although, basal synaptic transmission characteristics (input-output transfer and paired-pulse facilitation (PPF) ratio) were not significantly different between normal and HFD groups, the magnitudes of synaptic plasticity (long-term potentiation (LTP) and long-term depression (LTD)) were lower at the Schaffer collateral-CA1 synapses of the hippocampal slices isolated from the obese male, but not female, mice, as compared with their sex-specific controls. Our results suggest that male mice are more vulnerable than the females to the impacts of HFD on weight gains, metabolic alterations and deficits of learning, and hippocampal synaptic plasticity.