Increased peripheral lipid clearance in an animal model of amyotrophic lateral sclerosis

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, as 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 while gastro-instestinal absorption of lipids as well as peripheral clearance of triglycerides-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. Altogether, our findings show that energy metabolism in mSOD1 mice shifts towards an increase in the peripheral use of lipids. This metabolic shift probably accounts for the protective effect of dietary lipids in this model.