PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative 
disease targeting upper and lower motor neurons, inexorably leading to an early 
death. Defects in energy metabolism have been associated with ALS, including 
weight loss, increased energy expenditure, decreased body fat mass and increased 
use of lipid nutrients at the expense of carbohydrates. We review here recent 
findings on impaired energy metabolism in ALS, and its clinical importance.
RECENT FINDINGS: Hypothalamic atrophy, as well as alterations in hypothalamic 
peptides controlling energy metabolism, have been associated with metabolic 
derangements. Recent studies showed that mutations causing familial ALS impact 
various metabolic pathways, in particular mitochondrial function, and lipid and 
carbohydrate metabolism, which could underlie these metabolic defects in 
patients. Importantly, slowing weight loss, through high caloric diets, is a 
promising therapeutic strategy, and early clinical trials indicated that it 
might improve survival in at least a subset of patients. More research is needed 
to improve these therapeutic strategies, define pharmacological options, and 
refine the population of ALS patients that would benefit from these approaches.
SUMMARY: Dysfunctional energy homeostasis is a major feature of ALS clinical 
picture and emerges as a potential therapeutic target.