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How Sleep Loss Can Contribute to Adverse Weight Gain

In a new study, researchers show that overnight 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 impair our metabolism and adversely affect our body composition.

In the new study, the researchers studied 15 normal-weight healthy individuals who participated in two in-lab sessions in which activities and meal patterns were highly standardized. In random order, the participants slept a normal night's sleep (more than eight hours) during one session and were kept awake all night during the other session. The morning after each nighttime intervention, small tissue samples (biopsies) were taken from the participants' subcutaneous fat and skeletal muscles. These two tissues often exhibit impaired metabolism in conditions such as obesity and diabetes. At the same time, blood samples were taken in the morning to allow comparison between tissue compartments of a number of metabolites. These metabolites include sugar molecules, as well as various fatty acids and amino acids.

The tissue samples were used for multiple molecular analyses, which first 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 involved in regulating the way the genes of every cell in the body are turned on or off and is influenced by both hereditary and environmental factors, such as exercise.

Further analyzes of e.g. gene and protein expression showed that the response due to wakefulness differed between skeletal muscle and adipose tissue. The researchers say the wake period simulates the nighttime wake period of many shift workers who do night work. One possible explanation for why the two tissues respond in the observed manner may be that nighttime wakefulness has a tissue-specific effect on the circadian rhythm of the tissues, resulting in misalignment between these rhythms. This is something that the researchers found provisional support for, including in this study, as well as in an earlier similar but smaller study.

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 alignment would have affected the participants' tissue metabolism.