One Night Without Sleep Could Trigger Epigenetic Changes and Weight Gain

Even just one night of sleep loss could lead to epigenetic changes that tweak our metabolism and regulation of gene expression, a new study suggests. Researchers at Uppsala University found that one night without sleep was linked to alteration of the human epigenome, weight gain, and the loss of lean muscle mass.

Previous research has shown that skipping sleep lowers the body’s protective antioxidant levels and leads to epigenetic changes. Sleep deprivation can also impact histone modifications and impair memory. Now, a recent studied published in Science Advances sheds light on the molecular mechanisms connected to the disruption of our circadian clock, which is connected to an increase in fat and metabolic issues.

Lack of sleep in humans has been linked with weight gain, a reduction of lean muscle mass, and an increased risk for metabolic syndrome and diabetes, the authors mentioned. “Even minor weekly shifts in sleep timing, or as few as five consecutive nights of short sleep, have been associated with an increased risk of weight gain in healthy humans.” The mechanisms behind this process, however, aren’t well understood.

The research was conducted by Jonathan Cedernaes, PhD and colleagues at Uppsala University, Karolinska University, along with international collaborators. In the study, 15 healthy people were observed for two sessions in which they had a normal night of sleep or were kept awake throughout the entire night. Subcutaneous fat and skeletal muscle samples, as well as blood samples, were taken the morning after each session.

“Our research group was 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,” noted the researcher who led the study, Dr. Cedernaes.

Ultimately, the researchers found a tissue-specific adjustment to the levels of DNA methylation, a common epigenetic mechanism that regulates the expression of genes, often turning genes “off”. DNA methylation involves the addition of a methyl group to cytosine of DNA and is influenced by hereditary and environmental factors, including physical exercise.

“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,” said Cedernaes.

Interestingly, the group saw changes in DNA methylation only in adipose tissue. The alteration was specific to genes that have been previously shown to have significantly different DNA methylation levels present in metabolic conditions like type 2 diabetes and obesity. Epigenetic modifications have been shown to impart a metabolic “memory” that regulates long-term metabolic processes.

Cedernaes and his team believe that the DNA methylation changes they observed may constitute an additional piece of the puzzle of how sleep and circadian rhythm disruption can influence a person’s risk of developing diseases like obesity.

Many shift workers who are assigned to work in the evening are exposed to this period of overnight wakefulness. Additional epigenetic studies that assessed a person’s work environment have been published in the past, including the epigenetic difference found between office workers and nickel smelting workers.

The current research, however, only looks at the result of one night of losing sleep and the researchers aren’t certain of how other chronic sleep disruptions or changes to the circadian rhythm would influence someone’s tissue metabolism or gene expression.

“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,” explained Dr. Cedernaes.

The team also noticed changes in skeletal muscle levels of proteins involved in handling blood glucose, which could help explain why the participants’ glucose sensitivity was impaired after 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,” said Cedernaes.

Future research might touch upon sleep recovery, or how many days of typical sleep might normalize the metabolic and epigenetic changes that occurred as a result of sleep deprivation. Interestingly, exercise and diet have been shown to alter DNA methylation which could potentially counteract the negative metabolic impact of sleep loss.

Source: Cedernaes, J. et al. (2018). Acute sleep loss results in tissue-specific alterations in genome-wide DNA methylation state and metabolic fuel utilization in humans. Science Advances, 4(8).

Reference: Koffmar, L. How sleep loss may contribute to adverse weight gain. Uppsala Universitet Press Releases. 23 Aug 2018. Web.