Increased peripheral lipid clearance in an animal model of amyotrophic lateral sclerosis
Increased peripheral lipid clearance in an animal model of amyotrophic lateral sclerosis
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DOI：
10.1194/jlr.m700017-jlr200
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发表时间：
2007-07-01
影响因子：
6.5
通讯作者：
Loeffler, Jean-Philippe
中科院分区：
文献类型：
--
作者：
Fergani, Anissa;Oudart, Hugues;Loeffler, Jean-Philippe
肌萎缩侧索硬化症(ALS)是最常见的成人运动神经元疾病，可导致运动神经元变性、肌肉萎缩、瘫痪和死亡。尽管有这种退化过程，但在一大批患者中观察到了稳定的高代谢状态。表达突变形式的铜/锌超氧化物歧化酶的小鼠(mSOD1小鼠)构成了ALS的动物模型，与患者一样，表现出出人意料的能量消耗增加。通过高脂肪饮食来平衡这种增长，可以延长寿命，防止运动神经元丢失。在这里，我们调查了这种动物模型中是否存在脂质代谢缺陷。肝脂代谢基本正常，而胃肠对脂类的吸收以及富含甘油三酯的脂蛋白的外周清除明显增加，导致餐后血脂降低。这种缺陷通过通常诱导这些动物神经保护的高脂肪养生法得到纠正。总而言之，我们的发现表明，mSOD1小鼠的能量代谢转向增加外周脂肪的使用。这种代谢变化可能解释了饮食脂质在该模型中的保护作用。
Amyotrophic lateral sclerosis ( ALS) is the most common adult motor neuron disease, causing motor neuron degeneration, muscle atrophy, paralysis, and death. Despite this degenerative process, a stable hypermetabolic state has been observed in a large subset of patients. Mice expressing a mutant form of Cu/Zn-superoxide dismutase ( mSOD1 mice) constitute an animal model of ALS that, like patients, exhibits unexpectedly increased energy expenditure. Counterbalancing for this increase with a high-fat diet extends lifespan and prevents motor neuron loss. Here, we investigated whether lipid metabolism is defective in this animal model. Hepatic lipid metabolism was roughly normal, whereas gastrointestinal absorption of lipids as well as peripheral clearance of triglyceride-rich lipoproteins were markedly increased, leading to decreased postprandial lipidemia. This defect was corrected by the high-fat regimen that typically induces neuroprotection in these animals. Together, our findings show that energy metabolism in mSOD1 mice shifts toward an increase in the peripheral use of lipids. This metabolic shift probably accounts for the protective effect of dietary lipids in this model.