Plasticity of circadian clocks and consequences for metabolism

Abstract

The increased prevalence of metabolic disorders and obesity in modern society, together with the widespread use of artificial light at night, have led researchers to investigate whether altered patterns of light exposure contribute to metabolic disorders. This article discusses the experimental evidence that perturbed environmental cycles induce rhythm disorders in the circadian system, thus leading to metabolic disorders. This notion is generally supported by animal studies. Distorted environmental cycles, including continuous exposure to light, affect the neuronal organization of the central circadian pacemaker in the suprachiasmatic nucleus (SCN), its waveform and amplitude of the rhythm in electrical activity. Moreover, repeated exposure to a shifted light cycle or the application of dim light at night are environmental cues that cause a change in SCN function. The effects on the SCN waveform are the result of changes in synchronization among the SCN's neuronal cell population, which lead consistently to metabolic disturbances. Furthermore, we discuss the effects of sleep deprivation and the time of feeding on metabolism, as these factors are associated with exposure to disturbed environmental cycles. Finally, we suggest that these experimental studies reveal a causal relationship between the rhythm disorders and the metabolic disorders observed in epidemiological studies performed in humans. Keywords: circadian, desynchronization, suprachiasmatic nucleus, metabolic disorders, light Date submitted 11 April 2015; date of final acceptance 17 May 2015 Environmental Effects on the Rhythm of the SCNPerturbations in the circadian rhythm can develop under a variety of conditions, including ageing, neurodegenerative diseases and metabolic disorders. In order to effectively treat these diseases, it is important to elucidate the causal relationships behind these associations. Towards that end, several animal models have been used to specifically address the relationship between circadian disorders and metabolic disturbances. These models include transgenic mouse models with specific mutations in clock genes, as well as animals in which the function of the suprachiasmatic nucleus (SCN) has been altered by manipulating environmental cues. Transgenic models have been particularly valuable for elucidating the signalling pathways involved in the pathogenesis of metabolic disorders such as diabetes and obesity [1]. Moreover, performing complementary studies in wild-type animals and studying the effect of the environment on SCN functions are valuable as well, given the growing body of evidence suggesting that improper circadian timing interferes with health. For example, sleep disruption in humans is correlated with an increased risk of developing diabetes, and shift work has been associated with increased body mass index (BMI), altered plasma lipids and impaired insulin sensitivity [2][3][4] (Table 1). These studies indicate a potentially large influence of stable, robust environmental light-dark cycles on the maintenance o...

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