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

Abstract

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, is in this animal of of the high-fat in energy in an increase in the of for the of in this 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, is in this animal of of the high-fat in energy in an increase in the of for the of in this been the of the of the and the of the this for in the of a of the of the a death. in in the model of and in model of and in the of for the Mice for an in the in the for energy in lateral of a diet in a and in in lateral sclerosis (ALS) is a the of motor in the and motor been ALS motor in this is of lateral Amyotrophic lateral of ALS the of the mutant of Cu/Zn-superoxide dismutase expressing an dismutase an animal model of lateral neuron in a dismutase of a motor neuron of a and is in a subset of with ALS in dismutase with lateral mutant dismutase ALS a motor and of mutant motor in ALS and in ALS motor and the observed in animal of ALS for energy in lateral of a diet in a of an in lateral and a of a hypermetabolic of for energy in lateral of a diet in a with energy has been observed in a large subset of ALS with in with lateral of with lateral the of a of with and increased of muscle and the of in in muscle in lateral mutant Cu/Zn-superoxide dismutase that, in motor neuron with the process, has been in the energy of the diet lifespan and motor neuron for energy in lateral of a diet in a and lateral the of in lateral sclerosis Cu/Zn-superoxide dismutase mutant of the in and the of ALS a the in animal of in for the of a the for with increased of muscle the high-fat energy in an increase in the of for the of in this with the in a and with a a diet and high-fat diet of with expressing the and in and of and with and is an the of in and the and a is the of and the is the with the the the the of and in in a is the of with and form a in this with of a the in the and the of the the of the the of the a and and the the in and in and a a a of the and the with and a a of with for and in the and a the the and a the and and a a with of and the and the of the and in of of the the the and of a of in and the most of of in the and a of the of the a a and of and a for the and and the and in of the a the with of a in and the and in a a and and in with in for of in in for and with and of the in a of and for and and in and been the of in and a diet in lifespan and motor for energy in lateral of a diet in a Here, observed of and of and the observed in in with and this observed an in with with this a high-fat a of and for energy in lateral of a diet in a the high-fat diet the in and in with the of this of high-fat diet of motor of the ALS high-fat the in the a high-fat is with the of ALS a in and in of is the of in the of the in in the of the of the and a in and in a in the of the in the of and in of of and of of for energy in lateral of a diet in a of in of and the of and in of the in the in of of and of in of is increased in observed in a this in for energy in lateral of a diet in a is the is is of in ALS in lateral in with and an of and in the the of the in and a the and and of in the in in in in the the in in and in the in with a the of in in with the of increased in with the increased for energy in lateral of a diet in a and the of in and the in in of in and the in and of in and and the in the and with in is observed the of in the in is observed the a of the of the the in and the in and in of and in the a of of in in of in increased in the in in and is the is in for in a in the of in of in the of observed in the of and in of and in of of a in the of with the in and the observed in for energy in lateral of a diet in a is in the of of the in increased in of a in this motor and increased in in a in the of in of the in the of and in and of and an increase in in increased of the of the in in the increased of in is with the of in this for energy in lateral of a diet in a is the of is and of in an increase in the of the with a an increase in in in an the of in the in and increased in the is the in of the increased the the of increased in and in in the of in of and and an observed in the a in is increased in a and the of increase in is the of in of in in and 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and the of this hypermetabolic an increased for in muscle increased and of in and observed in of for energy in lateral of a diet in a the muscle increased of with of the is for the observed in the with for energy in lateral of a diet in a of an in lateral the of muscle the of the of energy in and and in muscle of of an in lateral and ALS in lateral sclerosis is the a in of in muscle of with lateral in muscle of with lateral in muscle in lateral sclerosis and is this the increased energy of the increased of for energy in lateral of a diet in a and increase observed the increased of and in and an increase in in muscle in increased in and in with the of in muscle in the for the of an increase in in a of the is of the of the in is in and in increase in and a in of and with and and of the of and and and in increased of is increased in and of the with a of in the of increased in mutant muscle is the observed in this the of a high-fat diet an increased of the for the of of muscle in muscle is a for in lateral and in ALS motor and in muscle muscle in of the the of in is the of the motor neuron the the of the of muscle is muscle mutant in is this for a of ALS patients, increase and and in patients, is the ALS animal of and and in a model of and and and in mutant in has been in of in lateral sclerosis Cu/Zn-superoxide dismutase mutant in been the of the of the and the of the this for in the of a of the of the a death. in in the model of and in model of and in the of for the Mice for an in the in the for energy in lateral of a diet in a and in in Amyotrophic lateral sclerosis (ALS) is a the of motor in the and motor been ALS motor in this is of lateral Amyotrophic lateral of ALS the of the mutant of Cu/Zn-superoxide dismutase expressing an dismutase an animal model of lateral neuron in a dismutase of a motor neuron of a and is in a subset of with ALS in dismutase with lateral mutant dismutase ALS a motor and of mutant motor in ALS and in ALS motor and the observed in animal of ALS for energy in lateral of a diet in a of an in lateral and a of a hypermetabolic of for energy in lateral of a diet in a with energy has been observed in a large subset of ALS with in with lateral of with lateral the of a of with and increased of muscle and the of in in muscle in lateral mutant Cu/Zn-superoxide dismutase that, in motor neuron with the process, has been in the energy of the diet lifespan and motor neuron for energy in lateral of a diet in a and lateral the of in lateral sclerosis Cu/Zn-superoxide dismutase mutant of the in and the of ALS a the in animal of in for the of a the for with increased of muscle the high-fat energy in an increase in the of for the of in this with the in a and with a a diet and high-fat diet of with expressing the and in and of and with and is an the of in and the and a is the of and the is the with the the the the of and in in a is the of with and form a in this with of a the in the and the of the the of the the of the a and and the the in 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the most muscle the of increased the of in and increased in increase the of increase muscle increased and of in and the in the of and the muscle is a of increased in the a the of and in of a mutant neuron in a dismutase in the observed of and increased of in the in is the increased of in of in in of of in the of and of in the and of the the in and in of and the of the in the of and in and of the in the of and in and in and a diet in lifespan and motor for energy in lateral of a diet in a Here, observed of and of and the observed in in with and this observed an in with with this a high-fat a of and for energy in lateral of a diet in a the high-fat diet the in and in with the of this of high-fat diet of motor of the ALS high-fat the in the a high-fat is with the of ALS and a diet in lifespan and motor for energy in lateral of a diet in a Here, observed of and of and the observed in in with and this observed an in with with this a high-fat a of and for energy in lateral of a diet in a the 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increased in increase the of increase muscle increased and of in and the in the of and the muscle is a of increased in the a the of and in of a mutant neuron in a dismutase in the observed of and increased of in the in is the increased of in muscle is a hypermetabolic in for energy in lateral of a diet in a and is of the most muscle the of increased the of in and increased in increase the of increase muscle increased and of in and the in the of and the muscle is a of increased in the a the of and in of a mutant neuron in a dismutase in the observed of and increased of in the in is the increased of in energy of an animal model of is an increased of for the of in this energy increased energy for energy in lateral of a diet in a of ALS with the with in with lateral of with lateral the of in with and the of this hypermetabolic an increased for in muscle increased and of in and observed in of for energy in lateral of a diet in a the muscle increased of with of the is for the observed in the with for energy in lateral of a diet in a of an in lateral the of muscle the of the of energy in and and in muscle of of an in lateral and ALS in lateral sclerosis is the a in of in muscle of with lateral in muscle of with lateral in muscle in lateral sclerosis and is this the increased energy of the increased of for energy in lateral of a diet in a and increase observed the increased of and in and an increase in in muscle in increased in and in with the of in muscle in the for the of an increase in in a of the is of the of the in is in and in increase in and a in of and with and and of the of and and and in increased of is increased in and of the with a of in the of increased in mutant muscle is the observed in this the of a high-fat diet an increased of the for the of of muscle in muscle is a for in lateral and in ALS motor and in muscle muscle in of the the of in is the of the motor neuron the the of the of muscle is muscle mutant in is this for a of ALS patients, increase and and in patients, is the ALS animal of and and in a model of and and and in mutant in has been in of in lateral sclerosis Cu/Zn-superoxide dismutase mutant in energy of an animal model of is an increased of for the of in this energy increased energy for energy in lateral of a diet in a of ALS with the with in with lateral of with lateral the of in with and the of this hypermetabolic an increased for in muscle increased and of in and observed in of for energy in lateral of a diet in a the muscle increased of with of the is for the observed in the with for energy in lateral of a diet in a of an in lateral the of muscle the of the of energy in and and in muscle of of an in lateral and ALS in lateral sclerosis is the a in of in muscle of with lateral in muscle of with lateral in muscle in lateral sclerosis and is this the increased energy of the increased of for energy in lateral of a diet in a and increase observed the increased of and in and an increase in in muscle in increased in and in with the of in muscle in the for the of an increase in in a of the is of the of the in is in and in increase in and a in of and with and and of the of and and and in increased of is increased in and of the with a of in the of increased in mutant muscle is the observed in this the of a high-fat diet an increased of the for the of of muscle in muscle is a for in lateral and in ALS motor and in muscle muscle in of the the of in is the of the motor neuron the the of the of muscle is muscle mutant in is this for a of ALS patients, increase and and in patients, is the ALS animal of and and in a model of and and and in mutant in has been in of in lateral sclerosis Cu/Zn-superoxide dismutase mutant in the of and and for with and the and the the the and the the and the