Obesity and Hypertriglyceridemia produce cognitive impairment
Obesity and Hypertriglyceridemia produce cognitive impairment
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DOI：
10.1210/en.2007-1722
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发表时间：
2008-05-01
期刊：
影响因子：
4.8
通讯作者：
Morley, John E.
中科院分区：
文献类型：
--
作者：
Farr, Susan A.;Yamada, Kelvin A.;Morley, John E.
肥胖与认知障碍有关。这种关联的长期机制包括高血糖、血脂异常或其他组成代谢综合征X的因素的后果。我们发现，代谢综合征X的主要血脂异常高甘油三酯血症是肥胖患者瘦素抵抗的部分原因。在这里，我们确定了甘油三酯是否对认知有直接和直接的影响。肥胖小鼠在三种不同的认知范式中表现出习得障碍：主动回避T迷宫、莫里斯水迷宫和食物奖励杠杆按压。这些损害不是由于足部电击敏感性、游泳速度、游泳距离或自愿饮用牛奶的差异造成的。通过使用吉非罗齐选择性降低甘油三酯，肥胖小鼠的认知受损得到改善。脑内注射三酸甘油酯，但不注射游离脂肪酸棕榈酸酯，损害了正常体重小鼠的习得。甘油三酯或牛奶(97%的脂肪是甘油三酯)，而不是脱脂牛奶(不含甘油三酯)，会损害海马体长期突触潜力的N-甲基-D-天冬氨酸成分的维持。吉非罗齐降低了整个大脑的氧化应激指标。我们的结论是，甘油三酯可能通过损害海马长时增强的N-甲基-D-天冬氨酸成分的维持来介导肥胖所见的认知障碍，并且降低甘油三酯可以逆转认知障碍并改善大脑中的氧化应激。
Obesity is associated with cognitive impairments. Long-term mechanisms for this association include consequences of hyperglycemia, dyslipidemia, or other factors comprising metabolic syndrome X. We found that hypertriglyceridemia, the main dyslipidemia of metabolic syndrome X, is in part responsible for the leptin resistance seen in obesity. Here we determined whether triglycerides have an immediate and direct effect on cognition. Obese mice showed impaired acquisition in three different cognitive paradigms: the active avoidance T-maze, the Morris water maze, and a food reward lever press. These impairments were not attributable to differences in foot shock sensitivity, swim speed, swimming distance, or voluntary milk consumption. Impaired cognition in obese mice was improved by selectively lowering triglycerides with gemfibrozil. Injection into the brain of the triglyceride triolein, but not of the free fatty acid palmitate, impaired acquisition in normal body weight mice. Triolein or milk (97% of fats are triglycerides), but not skim milk ( no triglycerides), impaired maintenance of the N-methyl-D-aspartate component of the hippocampal long-term synaptic potential. Measures of oxidative stress in whole brain were reduced by gemfibrozil. We conclude that triglycerides mediate cognitive impairment as seen in obesity, possibly by impairing maintenance of the N-methyl-D-aspartate component of hippocampal long-term potentiation, and that lowering triglycerides can reverse the cognitive impairment and improve oxidative stress in the brain.