出版社：American Society for Biochemistry and Molecular Biology
摘要：Amyotrophic lateral sclerosis (ALS) is the most common adultmotor neuron disease, causing motor neuron degeneration, muscleatrophy, paralysis, and death. Despite this degenerative process,a stable hypermetabolic state has been observed in a large subsetof patients. Mice expressing a mutant form of Cu/Zn-superoxidedismutase (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 extendslifespan and prevents motor neuron loss. Here, we investigatedwhether lipid metabolism is defective in this animal model.Hepatic lipid metabolism was roughly normal, whereas gastrointestinalabsorption of lipids as well as peripheral clearance of triglyceride-richlipoproteins were markedly increased, leading to decreased postprandiallipidemia. This defect was corrected by the high-fat regimenthat typically induces neuroprotection in these animals. Together,our findings show that energy metabolism in mSOD1 mice shiftstoward an increase in the peripheral use of lipids. This metabolicshift probably accounts for the protective effect of dietarylipids in this model.Supplementary key words plasma lipoproteins • neurodegeneration • motor neuron • low density lipoprotein • high density lipoprotein • liver metabolism • intestinal absorption • skeletal muscle
