Hypermetabolism appears to be an adverse prognostic biomarker in amyotrophic lateral sclerosis: a potential for therapeutic intervention?

Abstract

Click http://onlinelibrary.wiley.com/doi/10.1111/ene.13468/abstract to view the accompanying paper in this volume.

Changes in the concentrations of trimethylamine N-oxide (TMAO) and its precursors in patients with amyotrophic lateral sclerosis

“…In addition, as one of the important precursors of TMAO, carnitine is a critical component in the metabolism of long-chain fatty acids in the mitochondria of human cells 23 , 40 , 41 . The increased endogenous biosynthesis of carnitine in patients with ALS suggests a state of hypermetabolism and deficits in the metabolism of fatty acids, which have been reported in previous studies 13 , 42 – 44 . Defective energy metabolism and abnormal mitochondrial function partly explain the poor prognosis of patients with ALS 42 .…”

“…However, the data obtained in our study showed that the higher the concentration of carnitine in the plasma was, the less the involvement of UMNs. As mentioned above, since carnitine plays an important role in the metabolism of long-chain fatty acids, elevated concentrations of carnitine are a sign of hypermetabolism [42][43][44] . Several studies have confirmed that hypermetabolism is a factor leading to a poor prognosis in ALS, and less severe hypermetabolism may be www.nature.com/scientificreports/ an explanation for the better prognosis of patients with UMN-dominant ALS 43,44,46 .…”

“…As mentioned above, since carnitine plays an important role in the metabolism of long-chain fatty acids, elevated concentrations of carnitine are a sign of hypermetabolism [42][43][44] . Several studies have confirmed that hypermetabolism is a factor leading to a poor prognosis in ALS, and less severe hypermetabolism may be www.nature.com/scientificreports/ an explanation for the better prognosis of patients with UMN-dominant ALS 43,44,46 . In addition, the negative correlations between the involvement of UMNs and the concentrations of TMAO and other metabolites suggests that the inhibition of this metabolic pathway may lead to a better prognosis in patients with ALS.…”

Accelerated trans-sulfuration metabolically defines a discrete subclass of ALS patients

“…Overall, hypermetabolism is a feature of more than half of the ALS population and was recently shown to be a deleterious prognostic factor. Patients with hypermetabolism have a 20% worse prognosis than those that do not exhibit the hypermetabolism phenotype 30,31 . Until now, hypermetabolism in ALS has mostly been considered in relation to glucose metabolism.…”

Identification of a Distinct Metabolomic Subtype of Sporadic ALS Patients

“…Notably, hypermetabolism is a feature of more than half of the ALS population and was recently shown to be a deleterious prognostic factor for ALS. Indeed, patients with hypermetabolism have a 20% worse prognosis than those that do not exhibit the hypermetabolism phenotype 28,29 . Until now, hypermetabolism in ALS has mostly been considered in relation to glucose metabolism.…”