Rodent models to study the metabolic effects of shiftwork in humans

Abstract

Our current 24-h society requires an increasing number of employees to work nightshifts with millions of people worldwide working during the evening or night. Clear associations have been found between shiftwork and the risk to develop metabolic health problems, such as obesity. An increasing number of studies suggest that the underlying mechanism includes disruption of the rhythmically organized body physiology. Normally, daily 24-h rhythms in physiological processes are controlled by the central clock in the brain in close collaboration with peripheral clocks present throughout the body. Working schedules of shiftworkers greatly interfere with these normal daily rhythms by exposing the individual to contrasting inputs, i.e., at the one hand (dim)light exposure at night, nightly activity and eating and at the other hand daytime sleep and reduced light exposure. Several different animal models are being used to mimic shiftwork and study the mechanism responsible for the observed correlation between shiftwork and metabolic diseases. In this review we aim to provide an overview of the available animal studies with a focus on the four most relevant models that are being used to mimic human shiftwork: altered timing of (1) food intake, (2) activity, (3) sleep, or (4) light exposure. For all studies we scored whether and how relevant metabolic parameters, such as bodyweight, adiposity and plasma glucose were affected by the manipulation. In the discussion, we focus on differences between shiftwork models and animal species (i.e., rat and mouse). In addition, we comment on the complexity of shiftwork as an exposure and the subsequent difficulties when using animal models to investigate this condition. In view of the added value of animal models over human cohorts to study the effects and mechanisms of shiftwork, we conclude with recommendations to improve future research protocols to study the causality between shiftwork and metabolic health problems using animal models.

Central Circadian Clock Regulates Energy Metabolism

“…Shift workers who work from 10 pm to 6 am make up about 20% of working force in modern society (Antunes et al, 2010) and have a higher prevalence of obesity and heart disease (Karlsson et al, 2001; Kubo et al, 2011; Suwazono et al, 2008). Dim light at night or prolonged daily light exposure promotes obesity and metabolic disorders in animal models (Aubrecht et al, 2015; Kooijman et al, 2015; Opperhuizen et al, 2015). Housing mice under constant light caused arrhythmicity in locomotor activity, increased food intake, reduced energy expenditure, increased body fat mass, and impaired insulin sensitivity (Coomans et al, 2013a; Shi et al, 2013).…”

Disruption of the light cycle ablates diurnal rhythms in gastric vagal afferent mechanosensitivity

“…There are various animal models to mimic human shift work, including altering the timing of food intake, activity, sleep, or light exposure . Disruption of the light‐dark cycle has been shown to disrupt metabolic processes and have profound effects on mammalian physiology, however, the effect of a disrupted light‐dark cycle on gastric vagal afferent satiety signaling remains to be determined.…”

Shift in Food Intake and Changes in Metabolic Regulation and Gene Expression during Simulated Night-Shift Work: A Rat Model

“…Other studies in animals report inconsistent results regarding food intake during day- and night-shift work. A review of animal models of shift work and effects on metabolism found that effects depended on the species examined (rat or mouse) and the protocol used (manipulate timing of activity, light, food intake, and/or sleep) [21]. In human night workers, a recent meta-analysis reported no change in total calorie intake [26], although there are many other documented changes, such as timing of food intake, number, size, and nutritional content of meals [27].…”

“…Although several animal models indicate marked metabolic changes due to rest-work [21], only models involving relatively extreme rest-work schedules have been applied so far. The early metabolic effects of simulated night-shift work have yet to be investigated in animal models.…”