Best Practice & Research Clinical Endocrinology & Metabolism
6The impact of sleep disturbances on adipocyte function and lipid metabolism
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
References (60)
- et al.
Beneficial effects of subcutaneous fat transplantation on metabolism
Cell Metabolism
(2008) - et al.
Leptin regulation of neuroendocrine systems
Frontiers in Neuroendocrinology
(2000) - et al.
Transcriptional regulation of the leptin promoter by insulin-stimulated glucose metabolism in 3t3-l1 adipocytes
Biochemical and Biophysical Research Communications
(2001) - et al.
Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance
Lancet
(1996) - et al.
Preliminary observations on the effects of sleep time in a sleep restriction paradigm
Sleep Medicine
(2003) - et al.
Impact of sleep debt on metabolic and endocrine function
Lancet
(1999) - et al.
Serum leptin and vascular risk factors in obstructive sleep apnea
Chest
(2000) - et al.
Regulation of expression of ob mRNA and protein by glucocorticoids and cAMP
Journal of Biological Chemistry
(1996) - et al.
Hormonal effects of norepinephrine on acute glucose disposal in humans: a minimal model analysis
Metabolism
(1988) - et al.
Feast and famine: critical role of glucocorticoids with insulin in daily energy flow
Frontiers of Neuroendocrinology
(1993)
High-fat diet disrupts behavioral and molecular circadian rhythms in mice
Cell Metabolism
A sense of time: how molecular clocks organize metabolism
Trends in Endocrinology and Metabolism
Increased risk of ischaemic heart disease in shift workers
Lancet
Integration of hormonal and nutrient signals that regulate leptin synthesis and secretion
American Journal of Physiology – Endocrinology and Metabolism
Partial leptin deficiency and human adiposity
Nature
Positional cloning of the mouse obese gene and its human homologue
Nature
Marked and rapid decreases of circulating leptin in streptozotocin diabetic rats: reversal by insulin
American Journal of Physiology
Effects of nutritional status and aging on leptin gene expression in mice: importance of glucose
Hormone and Metabolic Research
Glucose metabolism rather than insulin is a main determinant of leptin secretion in humans
Journal of Clinical Endocrinology and Metabolism
Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes
Endocrinology
Nocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects
Journal of Clinical Investigation
Transient increase in obese gene expression after food intake or insulin administration
Nature
Diurnal variation in circulating leptin is dependent on gender, food intake and circulating insulin in mice
Acta Physiologica Scandinavica
Diurnal and ultradian rhythmicity of plasma leptin: effects of gender and adiposity
Journal of Clinical Endocrinology and Metabolism
Independent circadian and sleep/wake regulation of adipokines and glucose in humans
Journal of Clinical Endocrinology and Metabolism
Entrainment of the diurnal rhythm of plasma leptin to meal timing
Journal of Clinical Investigation
Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index
PLoS Medicine
Short sleep duration is associated with reduced leptin levels and increased adiposity: results from the Quebec family study
Obesity (Silver Spring)
Sleep loss reduces diurnal rhythm amplitude of leptin in healthy men
Journal of Neuroendocrinology
Leptin levels are dependent on sleep duration: relationships with sympathovagal balance, carbohydrate regulation, cortisol, and thyrotropin
Journal of Clinical Endocrinology and Metabolism
Cited by (46)
Metabolomics in sleep disorders
2024, Comprehensive Analytical ChemistryFood-derived antioxidant ergothioneine improves sleep difficulties in humans
2022, Journal of Functional FoodsCitation Excerpt :Interestingly, many acylcarnitines and fatty acids in the EGT intake group were significantly higher than that in the placebo group at week 4 (Fig. 5a) and were increased by the intervention (Fig. 5b). These substances are involved in lipid metabolism, which is reportedly associated with sleep in humans (Broussard & Brady, 2010). It has been shown that both low levels of acylcarnitine and the metabolic abnormalities in fatty acid β-oxidation are associated with narcolepsy in some patients (21%) (Miyagawa et al., 2011).
Diurnal rhythm of plasma EPA and DHA in healthy adults
2020, Prostaglandins Leukotrienes and Essential Fatty AcidsCitation Excerpt :For example, in one study wherein circadian variation was measured over a 28-h period, the acrophase of the majority of di- and triglycerides occurred in the morning whereas peaks in phosphatidylcholine (PC) species were observed in the evening [25]. Other trials have shown diurnal variation in plasma free fatty acids, with peak concentrations reported in the afternoon and evening [26,27]. Previous contradictory reports of the timing of the peak concentration of n-3 PUFAs specifically indicate that this occurred in the morning [15] or at lunchtime [16], whereas we observed these to occur in the evening.
Sleep Disorders and Gestational Diabetes Mellitus
2020, Neurological Modulation of Sleep: Mechanisms and Function of Sleep Health
- c
Tel.: 323 442 1919; Fax: 323 442 1918.