Impact of circadian misalignment on energy metabolism during simulated nightshift work

Abstract

Eating at a time when the internal circadian clock promotes sleep is a novel risk factor for weight gain and obesity, yet little is known about mechanisms by which circadian misalignment leads to metabolic dysregulation in humans. We studied 14 adults in a 6-d inpatient simulated shiftwork protocol and quantified changes in energy expenditure, macronutrient utilization, appetitive hormones, sleep, and circadian phase during day versus nightshift work. We found that total daily energy expenditure increased by ∼4% on the transition day to the first nightshift, which consisted of an afternoon nap and extended wakefulness, whereas total daily energy expenditure decreased by ∼3% on each of the second and third nightshift days, which consisted of daytime sleep followed by afternoon and nighttime wakefulness. Contrary to expectations, energy expenditure decreased by ∼12-16% during scheduled daytime sleep opportunities despite disturbed sleep. The thermic effect of feeding also decreased in response to a late dinner on the first nightshift. Total daily fat utilization increased on the first and second nightshift days, contrary to expectations, and carbohydrate and protein utilization were reduced on the second nightshift day. Ratings of hunger were decreased during nightshift days despite decreases in 24-h levels of the satiety hormones leptin and peptide-YY. Findings suggest that reduced total daily energy expenditure during nightshift schedules and reduced energy expenditure in response to dinner represent contributing mechanisms by which humans working and eating during the biological night, when the circadian clock is promoting sleep, may increase the risk of weight gain and obesity.

Keywords: appetite; diet-induced thermogenesis; eating at night; insufficient sleep; melatonin.

Fig. 1.

Study protocol. Open bars represent room light (<40 lx). Black bars represent scheduled polysomnography-recorded sleep. Time of day is plotted as relative clock hour with scheduled waketime arbitrarily assigned a value of 0800 hours and all other times referenced to this value. Shaded areas indicate scheduled wakefulness in dim light (<1 lx). B, breakfast; D, dinner; L, lunch; S, snack. Subjects were allowed three brief scheduled breaks per day to stand up and retrieve meals and use the toilet for bowel movements <3 m from the bed. Outside of scheduled breaks, subjects were given a urinal or bedpan when needed. Wakefulness and subject compliance during the constant posture protocol were verified via continuous monitoring by research staff and electroencephalography (EEG) recordings.

Fig. 2.

Hourly energy expenditure across the simulated shiftwork protocol (n = 14; P values, planned comparisons for day, two-tailed). The gray line represents day 2 (baseline), the black line is day 3 (nightshift 1), the blue line is day 4 (nightshift 2), and the red line is day 5 (nightshift 3). Black boxes along the x axis indicate scheduled sleep opportunities (day 2 nighttime, day 3 nap, days 4–5 daytime). *Differences between baseline and nightshift 1; ^#differences between baseline and nightshift 2; ^ǂdifferences between baseline and nightshift 3; ^†differences between nightshifts 1 and 2; ^‡differences between nightshifts 1 and 3; ^$differences between nightshifts 2 and 3; P < 0.05. Error bars are SEM.

Fig. 3.

Total daily (24-h) (A) and scheduled wakefulness (B) and sleep (C) energy expenditure (n = 14; P values, planned comparisons for day, two-tailed). Solid lines represent significant differences at the end of each line (modified Bonferroni, P < 0.025). Exploratory post hoc (ph) two-tailed P values are shown for scheduled sleep EE, as findings were in the opposite direction of that hypothesized. Error bars are SEM.

Fig. 4.

Appetitive hormones (A–C) [n = 14; P values, planned comparisons for day (24 h), one-tailed] and hunger ratings (D) (n = 14; P values, planned comparisons for day, two-tailed). Solid lines represent significant differences at the end of each line (modified Bonferroni, P < 0.025), and the dashed line represents a nonsignificant trend (P = 0.03). Error bars are SEM.