A great number of observational studies have suggested that sleep loss or disrupted circadian rhythms due to shift work are associated with obesity, type 2 diabetes and a variety of other dysfunctional metabolic conditions. A study from Uppsala University is now offering evidence that helps better explain how tissue-level molecular changes are brought on by sleep loss.

It's becoming clearer and clearer that disruptions to our circadian rhythms and interrupted or bad sleep can have a variety of negative health outcomes. Earlier this year a very large observational study concluded that night owls who tend to stay up late have a higher mortality risk and higher rates of diabetes and psychological or neurological disorders.

Obesity and weight gain have long been associated with bad or irregular sleep, and the most common hypothesis explaining this correlation was that chronic sleep deprivation tends to lead to inconsistent eating patterns and greater overall caloric intake. But what if these negative health outcomes are not simply due to eating junk food late at night? What if sleep loss actually results in more direct metabolic alterations at a tissue level?

A small study from a few years ago compared two groups of overweight subjects undergoing moderate caloric restriction. Over two weeks one group was limited to around five hours of sleep a night while the other group was allowed the minimum eight hours. The results found that the sleep deprived group struggled to lose as much weight as the control group suggesting that even with caloric restrictions, sleep loss can drastically alter a person's metabolism.

The new research out of Uppsala University took 15 healthy volunteers and subjected them to two overnight lab sessions. In one session they were allowed a regular eight hours of sleep and in the other they were kept awake all night. Following each session tissue biopsies were taken from both skeletal muscle and subcutaneous fat.

One of the initial observations was a highly specific increase in DNA methylation in subcutaneous adipose fat tissue. DNA methylation is the epigenetic process that regulates when certain genes are turned on or off, and it is particularly notable that this mechanism was observed to increase in fat tissue just after one single night of sleep disruption.

"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," explains lead on the new study, Jonathan Cedernaes.

Perhaps even more fascinating was the discovery of contrasting changes occurring in skeletal muscle samples after the sleep disruption. A process known as catabolism was identified as being triggered in that tissue. This mechanism indicates a breakdown of skeletal muscle proteins in the skeletal muscle. So these two different mechanisms suggested acute sleep loss can cause both a gain in fat mass and a loss of lean muscle.

"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 Cedernaes.

This research obviously has its limitations. These results were only gathered from a single night of sleep disruption and do not indicate whether they would remain consistent over a longer period of time. It is also unclear whether these mechanisms are triggered by other forms of circadian misalignment, such as someone who regularly works at night but still gets a regular eight hours of sleep every day.

Other longitudinal studies do still seem to suggest that night shift workers report higher rates of several metabolic diseases, so the evidence would indicate the human body can only mildly adapt to unusual circadian patterns. The next stages for this new research will be to examine how these metabolic tissue-level changes can be possibly counteracted.

"It will be interesting to investigate to what extent one or more nights of recovery sleep can normalize 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 Cedernaes.

The new study was published in the journal Science Advances.