Ceramides mediate cigarette smoke-induced metabolic disruption in mice.
Level 5 - mechanism / opinion, no new human data
Preclinical cell culture and animal model
PubMed 25269485 · doi:10.1152/ajpendo.00258.2014
What was done
Researchers evaluated how cigarette smoke exposure affects skeletal muscle insulin signaling and mitochondrial respiration using both cell and animal models. In vitro, cultured muscle cells were exposed to conditioned medium from cigarette smoke extract (CSE)-treated lung cells, with or without the ceramide synthesis inhibitor myriocin. In vivo, mice were subjected to daily cigarette smoke exposure and a high-fat, high-sugar (HFHS) diet, with or without myriocin injections to inhibit ceramide synthesis, and compared against control animals on standard diets.
What was found
The abstract does not report numerical values. Cultured muscle cells treated with CSE-exposed conditioned medium were completely unresponsive to insulin stimulation and exhibited severely blunted mitochondrial respiration; these effects were mitigated by myriocin pretreatment in lung cells. In mice, daily cigarette smoke exposure and HFHS diet elevated ceramides and caused insulin resistance. Myriocin injection protected against insulin resistance from smoke alone or HFHS diet alone, but was insufficient to prevent insulin resistance when smoke and HFHS diet were combined. However, myriocin restored muscle mitochondrial respiration across all treatment conditions.
Why it matters
This study outlines a mechanistic pathway wherein lung-derived ceramides from cigarette smoke enter circulation to impair skeletal muscle insulin sensitivity and mitochondrial function. Understanding this lung-muscle axis highlights ceramide biosynthesis as a potential target for smoking-related metabolic disease.
Limits
The study is limited to in vitro cell cultures and mouse models, meaning findings cannot be directly generalized to humans. The abstract does not provide sample sizes or exact quantitative metrics. Additionally, ceramide inhibition failed to fully rescue insulin resistance under combined cigarette smoke and high-fat, high-sugar dietary stress.
Cited by
- supports Exposure to cigarette smoke particles promotes ceramide accrual, forced mitochondrial fission, and insulin resistance.