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The impact of sleep disturbances on adipocyte function and lipid metabolism

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Classically, sleep has been considered to serve an essential restorative function for the brain. However, there are an increasing number of studies linking decreased sleep quantity and/or quality in humans to an increased obesity and diabetes risk. Reductions in sleep quantity or quality lead to an increase in hunger and appetite, which chronically could predispose an individual to obesity. Carefully controlled studies have shown that two nights of insufficient sleep is causally linked to a decrease in disposition index, the most commonly used predictor of an individual’s diabetes risk, and impairments in glucose tolerance and insulin sensitivity. Thus, sleep appears to play a critical role in modulating energy metabolism in peripheral tissues. Here we will discuss recent work implicating adipose tissue as a potential direct target of disruption of sleep quality, and explore the potential mechanistic links between sleep, adipose tissue and the global control of energy metabolism in humans.

Section snippets

Physiological role of the adipocyte in the body

Adipose tissue is an important insulin-sensitive tissue comprised of many cell types, the bulk of which are adipocytes. Commonly referred to as fat cells, adipocytes play a critical role for survival, serving as the central lipid storage depot that accounts for the vast majority of energy storage in mammals. In response to a meal and subsequent insulin signaling, adipocytes take up glucose and free fatty acids, which are stored primarily as triglycerides. The stored lipids are released for use

Regulation of leptin secretion by sleep

The identification of leptin as a regulated secreted peptide from adipocytes was a key development in the identification of adipose tissue as an endocrine organ.5 Despite intense research, the precise metabolic and molecular mechanisms by which leptin secretion is regulated remain incompletely understood, though insulin-stimulated glucose uptake and metabolism in adipose tissue appears to play a critical role. Leptin expression and secretion are associated with insulin-stimulated glucose uptake

Reduced sleep quantity and quality are associated with an increased risk of diabetes and obesity

The associations described above suggest that reduced sleep duration could lead to chronic alterations in leptin secretion and promote the development of obesity. Whether reduced sleep quality, independently of reduced sleep duration, could also impact adipocyte function and leptin release is unclear. However, there is a growing body of epidemiologic and laboratory evidence to indicate that sleep disturbances may result in insulin resistance and play a role in the risk of diabetes. For example,

Linking sleep disruptions to reduced insulin sensitivity – pointing towards the adipocyte

In light of the effects of reduced sleep duration and or quality on BMI, global insulin sensitivity, glucose tolerance and leptin secretion, it is important to consider the possible changes occurring at the cellular level that could mediate these observed systemic alterations. The body of epidemiologic, experimental and clinical evidence supporting the hypothesis that short and poor sleep is causally linked to insulin resistance and correlated with diabetes risk is rapidly growing. As such, it

Sympathetic nervous system

The autonomic nervous system controls aspects of involuntary physiology, such as heart rate and respiration, as well as signals to other peripheral organs. The autonomic nervous system can be divided into the parasympathetic and sympathetic nervous systems, the latter of which is activated during times of stress. This system is activated during the “fight or flight” response. The sympathetic nervous system is also regulated by sleep-wake cycles and its activity gradually decreases during the

The chicken vs. the egg: impact of dysregulation of adipocyte function on sleep and circadian rhythms

Increased stress responses via the coordinated activation of the sympathetic nervous system and the Hypothalamic–Pituitary–Adrenal axis are both possible contributors to the observed increase in risk of T2DM and obesity in the face of acute and chronic reductions in sleep duration and/or sleep quality. The mechanisms by which these processes may affect obesity and T2DM risk may be linked to a dysregulation at the cellular level of the adipocyte. We can also ask if the reverse is true: whether

Summary

Though sleep has historically been considered only necessary for the brain, recent work has established a link between disruptions in sleep quality and/or duration and a corresponding reduction in systemic insulin sensitivity. A molecular basis for the alterations in insulin signaling in peripheral tissue has not been elucidated but clearly must occur to account for the impact of sleep disturbances on energy metabolism, diabetes and obesity risk. Sleep may also play an essential role in

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