July 28, 2015
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One night of sleep loss may affect circadian genes, metabolic response

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One night of sleep loss can alter “clock genes” in the body, potentially leading to metabolic effects, including insulin resistance, according to research in The Journal of Clinical Endocrinology & Metabolism.

In a randomized study involving young adult men who experienced both overnight wakefulness and sleep in a laboratory setting, researchers found that acute sleep deprivation increased promoter methylation and reduced the transcription of circadian genes in a tissue-specific manner, and was linked to an impaired glucose response.

“As far as we know, we are the first to directly show that epigenetic changes can occur after sleep loss in humans, but also in these important tissues,” Jonathan Cedernaes, MD, PhD, of the department of neuroscience at Uppsala University in Sweden, said in a press release. “It was interesting that the methylation of these genes could be altered so quickly, and that it could occur for these metabolically important clock genes.”

Jonathan Cedernaes

Jonathan Cedernaes

Cedernaes and colleagues analyzed data from 15 healthy men (mean age, 22 years; mean BMI, 22.6 kg/m²) with normal sleep habits who underwent two experimental sessions consisting of one night of sleep and one night of sleep deprivation in random order, with each session separated by 4 weeks. Researchers provided all participants with breakfast, lunch and dinner during their 24-hour baseline period, followed by an 8.5-hour sleep opportunity during the first night. Participants were restricted to their bedrooms while awake. After the second night of each session, researchers obtained small adipose tissue samples from the stomach and muscle tissue from the thigh.

In adipose tissue, researchers found that acute sleep deprivation increased methylation in the promoter of CRY1 (P = .026) and in two promoter-interacting enhancer regions of PER1 (P = .026). In skeletal muscle, sleep deprivation decreased gene expression of BMAL1 (P = .033) and CRY1 (P = .025). Researchers also noted reduced concentrations of serum cortisol in participants after sleep deprivation, whereas postprandial plasma glucose concentrations were elevated when compared with participants who had a full night of sleep.

“This could suggest that these important molecular clocks are no longer synchronized between these two tissues,” Cedernaes said. “As such, ‘clock desynchrony’ between tissues has been linked to metabolic pathologies, [and] this could suggest that these tissue-specific changes were linked to the impaired glucose tolerance that our participants demonstrated after the night that they had been kept awake.”

Cedernaes noted that it remains unknown whether one or several nights of sleep could “reset” any negative metabolic effects.

“It could be that these changes are reset after one or several nights of sleep,” Cedernaes said. “On the other hand, epigenetic marks are suggested to be able to function a sort of metabolic memory, and have been found to be altered in shift workers and people suffering from type 2 diabetes. This could mean that some types of sleep loss or extended wakefulness, as in shift work, could lead to changes in the genome of your tissues that can affect your metabolism for longer periods.” by Regina Schaffer

Disclosure: The researchers report no relevant financial disclosures.