Mitochondrial fission mediates ceramide-induced metabolic disruption in skeletal muscle.
Level 5 - mechanism / opinion, no new human data
Preclinical in vitro and ex vivo laboratory research
PubMed 24073738 · doi:10.1042/BJ20130807
What was done
The authors assessed the effect of the sphingolipid ceramide on skeletal muscle mitochondrial structure and bioenergetics. Using cultured myotubes and permeabilized red gastrocnemius muscle fiber bundles, they evaluated mitochondrial division, mitochondrial oxygen consumption (respiration), hydrogen peroxide (H2O2) levels, and insulin signaling (Akt/PKB phosphorylation) in the presence of ceramide, with and without pharmacological inhibition or genetic knockdown of the fission mediator Drp1 (dynamin-related protein 1).
What was found
The abstract reports qualitative and directional findings without specific numerical values: - Ceramide induced rapid mitochondrial fission and increased Drp1 expression. - Ceramide decreased mitochondrial respiration in both cultured myotubes and permeabilized muscle fiber bundles. - Ceramide increased H2O2 levels and reduced Akt/PKB phosphorylation in myotubes. - Inhibition or knockdown of Drp1 prevented ceramide-induced mitochondrial division, maintained mitochondrial respiration, normalized H2O2 levels, and preserved insulin signaling.
Why it matters
These findings delineate a mechanism linking ceramide accumulation to skeletal muscle metabolic disruption and insulin resistance through Drp1-mediated mitochondrial fission.
Limits
The study was conducted entirely in vitro and ex vivo in cell cultures and isolated animal tissue bundles, which may not capture full in vivo or human physiology. The abstract provides no quantitative data, sample sizes, or statistical confidence intervals.
Cited by
- supports Exposure to cigarette smoke particles promotes ceramide accrual, forced mitochondrial fission, and insulin resistance.