The role of insufficient sleep and circadian misalignment in obesity

Abstract

Traditional risk factors for obesity and the metabolic syndrome, such as excess energy intake and lack of physical activity, cannot fully explain the high prevalence of these conditions. Insufficient sleep and circadian misalignment predispose individuals to poor metabolic health and promote weight gain and have received increased research attention in the past 10 years. Insufficient sleep is defined as sleeping less than recommended for health benefits, whereas circadian misalignment is defined as wakefulness and food intake occurring when the internal circadian system is promoting sleep. This Review discusses the impact of insufficient sleep and circadian misalignment in humans on appetite hormones (focusing on ghrelin, leptin and peptide-YY), energy expenditure, food intake and choice, and risk of obesity. Some potential strategies to reduce the adverse effects of sleep disruption on metabolic health are provided and future research priorities are highlighted. Millions of individuals worldwide do not obtain sufficient sleep for healthy metabolic functions. Furthermore, modern working patterns, lifestyles and technologies are often not conducive to adequate sleep at times when the internal physiological clock is promoting it (for example, late-night screen time, shift work and nocturnal social activities). Efforts are needed to highlight the importance of optimal sleep and circadian health in the maintenance of metabolic health and body weight regulation.

Fig. 1. Energy expenditure in healthy adults is influenced by both sleep and circadian processes.

a | Hourly 24-h energy expenditure with diet controlled for energy balance during a typical day with adequate sleep and one night of total sleep deprivation. b | The circadian rhythm of energy expenditure during a constant routine protocol; bottom graph shows percentage change for the circadian variation in energy expenditure (0° = melatonin onset, 360° = 24 hours after melatonin onset, where each 1 hour increment = 15°). Energy expenditure follows a circadian rhythm, with decreases in energy expenditure levels across the biological daytime, when levels of the hormone melatonin are low, and a trough in energy expenditure during early evening hours. During biological night-time, increases in energy expenditure occur when levels of melatonin are high (that is, 0 to ~180 circadian degrees), with a peak near the end of the biological night. c | Hourly 24-h energy expenditure during adequate sleep and insufficient sleep regardless of controlled or ad libitum diet. During sleep, energy is conserved, whereas energy expenditure during sleep deprivation (part a) and sleep restriction (part c) are similar to that of typical waking energy expenditure. d | Hourly 24-h energy expenditure during circadian misalignment with diet controlled for a typical day with adequate sleep; bottom graph shows the percentage change for sleeping energy expenditure during daytime and night-time sleep. If sleep is initiated during the daytime, energy expenditure is lower than during sleep under conditions of circadian alignment, resulting in an overall decreased 24-h energy expenditure. Figures show mean data with b-spline creating smooth curve fits. Note that energy expenditure plotted in parts a, b and d were assessed under bed rest conditions controlling for posture and activity, whereas energy expenditure in part c was assessed under ambulatory conditions in the whole-room calorimeter with two scheduled stair-stepping sessions each day. Grey panels show control sleep patterns and red panels show experimentally disrupted sleep patterns. Part a adapted with permission from ref., Wiley. Data for parts b–d from refs.^,,,,.

Fig. 2. The appetite-stimulating hormone ghrelin and the satiety hormones leptin and PYY are affected by energy intake, sleep and circadian rhythm in healthy adults.

The figure shows blood hormonal profiles during adequate sleep with diet controlled for energy balance at baseline as well as the circadian rhythm of these hormones during a constant routine protocol with hourly snacks. During conditions of habitual sleep timing with adequate sleep and an energy-balanced diet, levels of ghrelin peak near the beginning of sleep and decrease across the sleep episode (part a). From a circadian perspective, levels of ghrelin increase across the biological day and decrease across the biological night (part b). During conditions of habitual sleep timing with adequate sleep and an energy-balanced diet, levels of leptin are higher during sleep than during wakefulness, peak near the beginning of sleep and decrease thereafter (parts c), while levels of peptide-YY (PYY) are higher during wakefulness than during sleep (parts e). From a circadian perspective, levels of leptin decrease across the biological night and increase across the biological day; inset shows the percentage change for the circadian variation in leptin (part d). By contrast, levels of PYY increase across the biological night and decrease across the biological day (part f). Graphs show mean data with b-spline creating smooth curve fits. For comparison purposes, data for each hormone are plotted on the same scale. Parts a, c and e: Adequate sleep with diet controlled for energy balance at baseline. Parts b, d and f: circadian rhythm constant routine with hourly snacks. B, breakfast timing; D, dinner timing; L, lunch timing. Data from refs.^,.

Fig. 3. Model of changes in appetite hormones, hunger and energy intake in response to insufficient sleep.

The peripheral appetite-stimulating hormone ghrelin and the satiety hormones leptin and peptide-YY (PYY) feed back to the brain to influence appetite and hunger. When sleep is restricted but diet is controlled for the energy balance needed for a typical day with adequate sleep, the appetite-stimulating hormone ghrelin is increased and the satiety hormone leptin is decreased, resulting in increased hunger levels. By contrast, ghrelin is decreased and leptin and PYY are increased under an ad libitum diet during restricted sleep, reducing hunger levels. Changes in appetite hormones during ad libitum diets are probably due to increased energy intake during sleep restriction. However, energy intake remains excessive despite reductions in hunger, which suggests that other factors promote food intake. It is unknown how PYY might change during sleep restriction under a diet controlled for energy balance for a typical day with adequate sleep.

Fig. 4. Insufficient sleep affects energy intake and energy expenditure, which leads to a positive energy balance and the risk of weight gain.

During experimental conditions of insufficient sleep in healthy adults, when energy intake is designed to meet the energy balance demands for a typical day with adequate sleep at baseline, there is an increase in energy expenditure due to the increased wakefulness and a negative energy balance (that is, energy expended is greater than energy consumed). Concurrently, hunger will increase owing to changes in appetite hormones. However, if sleep is restricted and food is provided ad libitum, participants will eat far more calories than expended during the additional wakefulness despite changes in appetite hormones that would promote satiety. These extra calories put participants into a positive energy balance and weight gain if maintained over time. Moreover, the increase in calories occurs predominately in after-dinner snacks, a time in which the energetic response to energy intake is decreased, further promoting a positive energy balance and weight gain. +, Positive energy balance; –, negative energy balance.

Fig. 5. Circadian misalignment affects energy intake and appetite hormones, which potentially leads to a positive energy balance and the risk of weight gain.

During experimental conditions of circadian misalignment in healthy adults, when energy intake is designed to meet energy balance demands for a typical day with adequate night-time sleep at baseline, there is a decrease in 24-h energy expenditure predominantly due to decreased sleeping energy expenditure. Hunger might increase owing to changes in appetite hormones, but hunger might also decrease owing to the circadian variation in hunger that shows lower hunger levels during the biological night-time than during the biological daytime. Alternations in food choices and eating during the biological night might also contribute to weight gain. Pathways with limited evidence are indicated with ‘?’. +, positive energy balance; PYY, peptide-YY.