Summary: Researchers report just one night of sleep loss can have a tissue specific impact on metabolism and the regulation of gene expression. The study could explain why those who suffer chronic sleep loss or work shifts are at greater risk of obesity and type 2 diabetes.Source: Uppsala University.In a new study, researchers at Uppsala University now demonstrate that one night of sleep loss has a tissue-specific impact on the regulation of gene expression and metabolism in humans. This may explain how shift work and chronic sleep loss impairs our metabolism and adversely affects our body composition. The study is published in the scientific journal Science Advances.Epidemiological studies have shown that the risk for obesity and type 2 diabetes is elevated in those who suffer from chronic sleep loss or who carry out shift work. Other studies have shown an association between disrupted sleep and adverse weight gain, in which fat accumulation is increased at the same time as the muscle mass is reduced – a combination that in and of itself has been associated with numerous adverse health consequences. Researchers from Uppsala and other groups have in earlier studies shown that metabolic functions that are regulated by e.g. skeletal muscle and adipose tissue are adversely affected by disrupted sleep and circadian rhythms. However, until now it has remained unknown whether sleep loss per se can cause molecular changes at the tissue level that can confer an increased risk of adverse weight gain.In the new study, the researchers studied 15 healthy normal-weight individuals who participated in two in-lab sessions in which activity and meal patterns were highly standardised. In randomised order, the participants slept a normal night of sleep (over eight hours) during one session, and were instead kept awake the entire night during the other session. The morning after each night-time intervention, small tissue samples (biopsies) were taken from the participants’ subcutaneous fat and skeletal muscle. These two tissues often exhibit disrupted metabolism in conditions such as obesity and diabetes. At the same time in the morning, 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 first of all revealed that the sleep loss condition resulted in a tissue-specific change in DNA methylation, one form of mechanism that regulates gene expression. DNA methylation is a so-called epigenetic modification that is involved in regulating how the genes of each cell in the body are turned on or off, and is impacted by both hereditary as well as environmental factors, such as physical exercise.“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,” says Jonathan Cedernaes who led the study.“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. 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,” notes Jonathan Cedernaes.Further analyses of e.g. 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.The tissue samples were used for multiple molecular analyses, which first of all revealed that the sleep loss condition resulted in a tissue-specific change in DNA methylation, one form of mechanism that regulates gene expression. NeuroscienceNews.com image is in the public domain.“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.[divider]About this neuroscience research article[/divider]Funding: AFA Försäkring, Novo Nordisk Foundation, Swedish SciLife, LabSwedish Brain Foundation, Swedish Research Council, Åke Wibe funded this study.See alsoFeaturedGeneticsNeurosciencePsychology·February 12, 2020Multi-center neuroimaging study offers new insights on schizophreniaSource: Jonathan Cedernaes – Uppsala University Publisher: Organized by NeuroscienceNews.com. Image Source: NeuroscienceNews.com image is in the public domain. Original Research: Open access research for “Acute sleep loss results in tissue-specific alterations in genome-wide DNA methylation state and metabolic fuel utilization in humans” by Jonathan Cedernaes, Milena Schönke, Jakub Orzechowski Westholm, Jia Mi, Alexander Chibalin, Sarah Voisin, Megan Osler, Heike Vogel, Katarina Hörnaeus, Suzanne L. Dickson, Sara Bergström Lind, Jonas Bergquist, Helgi B Schiöth, Juleen R. Zierath and Christian Benedict in Science Advances. Published August 22 2018. doi:10.1126/sciadv.aar8590[divider]Cite This NeuroscienceNews.com Article[/divider][cbtabs][cbtab title=”MLA”]Uppsala University”How Sleep May Contribute to Adverse Weight Gain.” NeuroscienceNews. NeuroscienceNews, 26 August 2018. <https://neurosciencenews.com/sleep-weight-gain-9743/>.[/cbtab][cbtab title=”APA”]Uppsala University(2018, August 26). How Sleep May Contribute to Adverse Weight Gain. NeuroscienceNews. Retrieved August 26, 2018 from https://neurosciencenews.com/sleep-weight-gain-9743/[/cbtab][cbtab title=”Chicago”]Uppsala University”How Sleep May Contribute to Adverse Weight Gain.” https://neurosciencenews.com/sleep-weight-gain-9743/ (accessed August 26, 2018).[/cbtab][/cbtabs]AbstractAcute sleep loss results in tissue-specific alterations in genome-wide DNA methylation state and metabolic fuel utilization in humansCurtailed sleep promotes weight gain and loss of lean mass in humans, although the underlying molecular mechanisms are poorly understood. We investigated the genomic and physiological impact of acute sleep loss in peripheral tissues by obtaining adipose tissue and skeletal muscle after one night of sleep loss and after one full night of sleep. We find that acute sleep loss alters genome-wide DNA methylation in adipose tissue, and unbiased transcriptome-, protein-, and metabolite-level analyses also reveal highly tissue-specific changes that are partially reflected by altered metabolite levels in blood. We observe transcriptomic signatures of inflammation in both tissues following acute sleep loss, but changes involving the circadian clock are evident only in skeletal muscle, and we uncover molecular signatures suggestive of muscle breakdown that contrast with an anabolic adipose tissue signature. Our findings provide insight into how disruption of sleep and circadian rhythms may promote weight gain and sarcopenia.[divider]Feel free to share this Neuroscience News.[/divider]Join our Newsletter I agree to have my personal information transferred to AWeber for Neuroscience Newsletter ( more information )Sign up to receive the latest neuroscience headlines and summaries sent to your email daily from NeuroscienceNews.comWe hate spam and only use your email to contact you about newsletters. We do not sell email addresses. You can cancel your subscription any time.