While staring at the alarm clock isn’ta great way to catch a healthy night’s sleep, the lull of our circadian rhythm most certainly is. The circadian clock keeps our cells and their epigenomes in shape by maintaining synchrony with the day, and now new findings from the lab of Christian Benedict at Uppsala University (Sweden) show that missing only a single night’s sleep can alter the DNA methylation of obesity and diabetes genes in our fat cells.
The talented team compared parallel samples of adipose tissue, skeletal muscle, and blood samples from 15 healthy young human male volunteers the morning after one night of sleep loss or one regular night of sleep. They gave the samples the full molecular treatment: the 450k array examined DNA methylation, RNA-seq interrogated gene expression, and mass spectrometry tackled both relative protein concentrations and metabolomic analyses.
First author Jonathan Cedernaes shares, “Our research group were the first to demonstrate that acute sleep loss in and of itself results in epigenetic changes in the so-called clock genes that within each tissue regulate its circadian rhythm. Our new findings indicate that sleep loss causes tissue-specific changes to the degree of DNA methylation in genes spread throughout the human genome. Our parallel analysis of both muscle and adipose tissue further enabled us to reveal that DNA methylation is not regulated similarly in these tissues in response to acute sleep loss.
“It is interesting that we saw changes in DNA methylation only in adipose tissue, and specifically for genes that have also been shown to be altered at the DNA methylation level in metabolic conditions such as obesity and type 2 diabetes. Epigenetic modifications are thought to be able to confer a sort of metabolic “memory” that can regulate how metabolic programmes operate over longer time periods. Wethereforethink that the changes we have observed in our new study can constitute another piece of the puzzle of how chronic disruption of sleep and circadian rhythms may impact the risk of developing for example obesity.”
“In the present study we observed molecular signatures of increased inflammation across tissues in response to sleep loss. However, we also saw specific molecular signatures that indicate that the adipose tissue is attempting to increase its capacity to store fat following sleep loss, whereas we instead observed signs indicating concomitant breakdown of skeletal muscle proteins in the skeletal muscle, in what’s also known as catabolism. We also noted changes in skeletal muscle levels of proteins involved handling blood glucose, and this could help explain why the participants’ glucose sensitivity was impaired following sleep loss. Taken together, these observations may provide at least partial mechanistic insight as to why chronic sleep loss and shift work can increase the risk of adverse weight gain as well as the risk of type 2 diabetes.”
“It will be interesting to investigate to what extent one or more nights of recovery sleep can normalise the metabolic changes that we observe at the tissue level as a result of sleep loss. Diet and exercise are factors that can also alter DNA methylation, and these factors can thus possibly be used to counteract adverse metabolic effects of sleep loss.”