Insulin resistance is a main determinant in the development of type 2 diabetes mellitus. Here, the authors review the physiological links between circadian clocks and insulin sensitivity and present current evidence for a relationship between circadian disruption and insulin resistance.
Circadian rhythms in endocrinology and metabolism
Circadian rhythms are regular, daily cycles of biological processes, including predictable variations in the circulating levels of hormones. The circadian system, the function of which is controlled by the suprachiasmatic nucleus in the hypothalamus, is integral to a multitude of endocrine and neuroendocrine processes, including metabolism, energy balance and appetite control. Furthermore, the circadian system is implicated in a number of diseases and disruption of the circadian system (known as circadian dysrhythmia), which can result from modern lifestyle changes such as shift work, is associated with an increasing health burden globally. For instance, obesity and type 2 diabetes mellitus, two leading causes of disease and death worldwide, have been linked to circadian dysrhythmia. In this article series, Nature Reviews Endocrinology examines the mechanisms linking circadian rhythms with endocrinology and metabolism, and the implications of circadian dysrhythmia for diseases of the endocrine system.
Exercise is used to prevent and treat metabolic diseases. Finding the optimum time for exercise is important as skeletal muscle has many clock-controlled genes. This Review summarizes the current literature regarding the consequence of exercise at different times of the day.
In this Review, Etienne Challet discusses the dual modulation of food intake by homeostatic and circadian processes, describes the mechanisms regulating feeding time and highlights the beneficial effects of correctly timed eating, as opposed to the negative metabolic consequences of mistimed eating.
The human stress response has evolved to maintain homeostasis under conditions of stress. This Review outlines the role of the hypothalamic–pituitary–adrenal axis in synchronizing the stress response with circadian regulatory processes and maintaining homeostasis.
Daily TSH secretion profiles are disrupted in some patients with hypothyroidism and hyperthyroidism. Here, the authors discuss the interconnection between circadian clocks and thyroid function and highlight the possible link between thyroid cancer and disrupted circadian machinery
Food is widely assumed to be a zeitgeber, or time cue, for the human circadian system; however, evidence from human trials is scarce. This Review highlights evidence from human studies that food is a zeitgeber and compares findings against formal zeitgeber criteria.
Disruption of the circadian system can alter microbiome communities and can perturb host metabolism leading to the metabolic syndrome. This Perspective discusses the role of intestinal microbiota in mediating the effects circadian dysrhythmia on human health.
News & comment
A cross-sectional study shows that proxies of circadian misalignment, such as late chronotype and social jet lag, are associated with increased adiposity in adolescent girls but not adolescent boys, highlighting a potential sex-specific effect of circadian misalignment. Interventions targeting sleep timing should be considered in the prevention of adolescent obesity.
A recent study shows that a history of rotating night-shift work and an unhealthy lifestyle are associated with increased risk of type 2 diabetes mellitus (T2DM), both independently and synergistically. This is the first large-scale, prospective study to quantify how a healthy lifestyle might partially offset T2DM risk in shift workers.
Exercise is the elixir of health. However, timing can boost or blunt exercise performance and health benefits. Two complementary studies used transcriptomic and metabolomic tools to dissect how time of day affects the impact of exercise. The findings open new avenues for optimizing timing of physical activity to boost its benefits further.
Many cardiovascular functions and the onset of adverse cardiovascular events are influenced by the circadian rhythm that exists in all cell types. In this Review, the authors summarize the role of the molecular clock in cardiovascular physiology and disease and suggest how circadian rhythms can be exploited, such as in chronotherapy, or targeted therapeutically.
In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus acts as the principal pacemaker for circadian rhythms, which are powerful regulators of physiology and behaviour. In this Review, Hastings, Maywood and Brancaccio examine the molecular, cellular and circuit mechanisms underlying time-keeping in the SCN.
Circadian rhythms align organismal functions with phases of rest and activity. Accordingly, circadian oscillations occur in many physiological processes, including various metabolic functions. In turn, metabolic cues are emerging as regulators of the circadian clock. This crosstalk between metabolism and circadian rhythms has important implications for human health.
In addition to the central pacemaker, the mammalian brain contains additional circadian clocks. In this Review, Greco and Sassone–Corsi discuss how systemic homeostasis relies on the coordinated communication between these clocks.