Circadian Disruption Leads to Insulin Resistance and Obesity

Shi, Shu-qun; Ansari, Tasneem; McGuinness, Owen P.; Wasserman, David H.; Johnson, Carl Hirschie

doi:10.1016/j.cub.2013.01.048

Cited by 389 publications

(310 citation statements)

References 54 publications

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“…It also regulates daily rhythms of insulin secretion and glucose metabolism, either in a direct or indirect manner. In both humans and rodents, there are robust daily rhythms of glucose tolerance and insulin sensitivity [8,12,13]. Disturbances of the sleep/wake cycle, reduced sleep duration/quality and altered sleep architecture can impair these rhythms, likely contributing to the development of metabolic disease [14][15][16][17][18].…”

Section: The Internal Timing System and Metabolic Dysfunctionmentioning

confidence: 99%

“…Without question, poor diet, lack of exercise, obesity and chronic insulin resistance are major contributing factors. One basic function that appears to be heavily influenced by (and also influences) obesity and metabolic disease is the internal timing system [6][7][8][9][10]. The timing system drives daily rhythms of physiology and behaviour, including the alternating pattern of feeding and fasting [11].…”

Section: The Internal Timing System and Metabolic Dysfunctionmentioning

confidence: 99%

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Chronomedicine and type 2 diabetes: shining some light on melatonin

et al. 2016

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In mammals, the circadian timing system drives rhythms of physiology and behaviour, including the daily rhythms of feeding and activity. The timing system coordinates temporal variation in the biochemical landscape with changes in nutrient intake in order to optimise energy balance and maintain metabolic homeostasis. Circadian disruption (e.g. as a result of shift work or jet lag) can disturb this continuity and increase the risk of cardiometabolic disease. Obesity and metabolic disease can also disturb the timing and amplitude of the clock in multiple organ systems, further exacerbating disease progression. As our understanding of the synergy between the timing system and metabolism has grown, an interest has emerged in the development of novel clock-targeting pharmaceuticals or nutraceuticals for the treatment of metabolic dysfunction. Recently, the pineal hormone melatonin has received some attention as a potential chronotherapeutic drug for metabolic disease. Melatonin is well known for its sleep-promoting effects and putative activity as a chronobiotic drug, stimulating coordination of biochemical oscillations through targeting the internal timing system. Melatonin affects the insulin secretory activity of the pancreatic beta cell, hepatic glucose metabolism and insulin sensitivity. Individuals with type 2 diabetes mellitus have lower night-time serum melatonin levels and increased risk of comorbid sleep disturbances compared with healthy individuals. Further, reduced melatonin levels, and mutations and/or genetic polymorphisms of the melatonin receptors are associated with an increased risk of developing type 2 diabetes. Herein we review our understanding of molecular clock control of glucose homeostasis, detail the influence of circadian disruption on glucose metabolism in critical peripheral tissues, explore the contribution of melatonin signalling to the aetiology of type 2 diabetes, and discuss the pros and cons of melatonin chronopharmacotherapy in disease management.

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Section: The Internal Timing System and Metabolic Dysfunctionmentioning

confidence: 99%

Section: The Internal Timing System and Metabolic Dysfunctionmentioning

confidence: 99%

Chronomedicine and type 2 diabetes: shining some light on melatonin

et al. 2016

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“…Likewise other physiological functions, glucose metabolism is regulated by circadian system (43,44). In an experiment, study Clock mutant mice showed lack of rhythmicity in the action of insulin, a condition which was reversible once the clock protein was reintroduced (43). The removal of pancreatic Clock and Bmal1 in mice resulted in functional defects in insulin secretion and decreases in islet size and survival, signifies a key role of peripheral clocks in the regulation of glucose homeostasis (45).…”

Section: Melatonin and Circadian Rhythmmentioning

confidence: 99%

Section: Melatonin and Circadian Rhythmmentioning

confidence: 99%

The role of melatonin in diabetes: therapeutic implications

Sharma

Singh

Ahmad

et al. 2015

Arch. Endocrinol. Metab.

110

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Melatonin referred as the hormone of darkness is mainly secreted by pineal gland, its levels being elevated during night and low during the day. The effects of melatonin on insulin secretion are mediated through the melatonin receptors (MT1 and MT2). It decreases insulin secretion by inhibiting cAMP and cGMP pathways but activates the phospholipaseC/IP3 pathway, which mobilizes Ca 2+ from organelles and, consequently increases insulin secretion. Both in vivo and in vitro, insulin secretion by the pancreatic islets in a circadian manner, is due to the melatonin action on the melatonin receptors inducing a phase shift in the cells. Melatonin may be involved in the genesis of diabetes as a reduction in melatonin levels and a functional interrelationship between melatonin and insulin was observed in diabetic patients. Evidences from experimental studies proved that melatonin induces production of insulin growth factor and promotes insulin receptor tyrosine phosphorylation. The disturbance of internal circadian system induces glucose intolerance and insulin resistance, which could be restored by melatonin supplementation. Therefore, the presence of melatonin receptors on human pancreatic islets may have an impact on pharmacotherapy of type 2 diabetes. Arch Endocrinol Metab.2015;59(5):391-9

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“…A causal role for a disturbed circadian rhythm in the development of obesity has been demonstrated by animal studies. Mice with genetically dysfunctional clock genes develop obesity and insulin resistance (6)(7)(8)(9). Moreover, specific ablation of the SCN induces acute weight gain (10).…”

mentioning

confidence: 99%

Prolonged daily light exposure increases body fat mass through attenuation of brown adipose tissue activity

Kooijman¹,

Berg²,

Ramkisoensing

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

124

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Disruption of circadian rhythmicity is associated with obesity and related disorders, including type 2 diabetes and cardiovascular disease. Specifically, prolonged artificial light exposure associates with obesity in humans, although the underlying mechanism is unclear. Here, we report that increasing the daily hours of light exposure increases body adiposity through attenuation of brown adipose tissue (BAT) activity, a major contributor of energy expenditure. Mice exposed to a prolonged day length of 16-and 24-h light, compared with regular 12-h light, showed increased adiposity without affecting food intake or locomotor activity. Mechanistically, we demonstrated that prolonged day length decreases sympathetic input into BAT and reduces β3-adrenergic intracellular signaling. Concomitantly, prolonging day length decreased the uptake of fatty acids from triglyceride-rich lipoproteins, as well as of glucose from plasma selectively by BAT. We conclude that impaired BAT activity is an important mediator in the association between disturbed circadian rhythm and adiposity, and anticipate that activation of BAT may overcome the adverse metabolic consequences of disturbed circadian rhythmicity. M odern world society is subjected to disturbances of circadian rhythms by shift work, sleep deprivation, and environmental light pollution. Importantly, the increasing prevalence of obesity is associated with a disrupted sleep-wake pattern in humans (1) and coincides with the availability of artificial light (2, 3). Additionally, a recent study revealed a relationship between exposure to light at night and obesity in a cross-sectional analysis of over 100,000 women (4). Light input is the most important cue for generation of circadian (∼24 h) rhythms by the master clock. Both in rodents and humans the master clock is situated in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN is responsible for synchronization of peripheral clocks throughout the body, which is mediated by endocrine and neuronal signals (5). A causal role for a disturbed circadian rhythm in the development of obesity has been demonstrated by animal studies. Mice with genetically dysfunctional clock genes develop obesity and insulin resistance (6-9). Moreover, specific ablation of the SCN induces acute weight gain (10). These results indicate a crucial role for the SCN in the regulation of adiposity.Interestingly, we previously showed that prolonged light exposure only is sufficient to enhance weight gain in mice. Constant light disrupts the central circadian clock, evidenced by an immediate reduction in the circadian amplitude of SCN electrical activity. Moreover, constant light induces body weight gain and insulin resistance, even faster than high-fat diet, which was not caused by increased food intake or reduced locomotor activity (11). Therefore, disruption of the central biological clock likely induces weight gain by decreasing energy expenditure.Recently, it has been recognized that brown adipose tissue (BAT) importantly contributes to energy ...

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Circadian Disruption Leads to Insulin Resistance and Obesity

Cited by 389 publications

References 54 publications

Chronomedicine and type 2 diabetes: shining some light on melatonin

Chronomedicine and type 2 diabetes: shining some light on melatonin

The role of melatonin in diabetes: therapeutic implications

Prolonged daily light exposure increases body fat mass through attenuation of brown adipose tissue activity

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