Working in night shift and chronic sleep loss adversely impairs our body’s metabolism and composition according to a new study, conducted by researchers from Uppsala University, published in the scientific journal Science Advances.
The risk of obesity and type 2 diabetes too is elevated in those who suffer from chronic sleep loss or work in night shift, according to epidemiological studies.
Scientists have also corroborated the linkage between disturbed sleep and weight gain, leading to increased fat accumulation and reduced muscle mass – associated with adverse health consequences.
Earlier studies by researchers from Uppsala and other groups have demonstrated how metabolic functions — regulated by skeletal muscle and adipose tissue are adversely affected by disrupted sleep and circadian rhythms. However, until now it was not clear how sleep loss could cause tissue level molecular changes and increase the weight gain.
In the new study, researchers studied 15 healthy normal-weight individuals in two highly standardized in-lab sessions with activity and meal patterns. The participants (picked up in random order) were allowed to sleep normally for over eight hours during one session, and kept awake for the entire night during the other session. In the next morning tissue samples (biopsies) were taken from the participants’ subcutaneous fat and skeletal muscle. The tissue exhibits depicted the effects of disrupted metabolism leading to obesity and diabetes. At the same time, blood samples were also taken to enable a comparison across tissue compartments of a number of metabolites. These metabolites comprise sugar molecules, as well as different fatty and amino acids.
The tissue samples were used for multiple molecular analyses, which revealed how sleep loss resulted in a tissue-specific change in DNA methylation– an epigenetic modification that is involved in regulating how the genes of each cell are turned on or off and impacted by hereditary as well as environmental factors like physical exercise.
“Our research group was the first to demonstrate how acute sleep loss results in epigenetic changes in the clock genes that within each tissue and 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,” says Jonathan Cedernaes who led the study.
“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 programs operate over longer time periods. We therefore think 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,” says Jonathan Cedernaes.
Further analyses of gene and protein expression demonstrated that the response as a result of wakefulness differed between skeletal muscle and adipose tissue. The researchers say that the period of wakefulness simulates the overnight wakefulness period of many shift workers assigned to nightwork. A possible explanation for why the two tissues respond in the observed manner could be that overnight wakefulness periods exert a tissue-specific effect on tissues’ circadian rhythm, resulting in misalignment between these rhythms. This is something that the researchers found preliminary support for also in this study, as well as in an earlier similar but smaller study.
“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,” says Jonathan Cedernaes.
The researchers have only studied the effect of one night of sleep loss, and therefore do not know how other forms of sleep or disruption of circadian misalignment would have affected the participants’ tissue metabolism.
“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,” says Jonathan Cedernaes.
