Acute and chronic effects of rotating shift work on running wheel activity, energy balance, and molecular alterations

Endogenous molecular clocks influence physiology, metabolism, and behavior. Shift workers are exposed to repeated changes in the timing of light, feeding, and activity and, consequently, are at increased risk for development of chronic disease associated with disruptions of circadian rhythms. The objectives of this research were to determine the behavioral, physiological, and molecular effects of acute and chronic exposure to rotating shift work (RSW) using murine models and evaluate the effects of timed exercise and timed feeding independently and in combination, within the context of high and low-fat diets, in a model of chronic rotating shift work (CRSW). To simulate human RSW, mice were housed in either normal or RSW conditions, consisting of 12-hour shifts in the light/dark cycle every 3 or 4 days for either 3- or 14-day in the acute experiment (RSW) or 10 weeks in the chronic experiment (CRSW). Under CRSW, six groups of mice were examined for metabolic and behavioral outcomes, including control (C), shift work control (SC), shift work chronic exercise (S-RW), shift work timed exercise (S-TE), shift work timed feeding (S-TF), and shift work timed exercise and feeding (S-TFEX). We report disrupted wheel running activity patterns in acute and chronic exposure to RSW. Differential effects of low- and high-fat diet were observed in wheel running activity in CRSW. Substantial alterations in the diurnal expression of core clock and metabolic genes were observed in a tissue-specific manner. After 14 days of RSW exposure, most tissues lost complete clock rhythmicity and resulted in impaired fasting glucose. CRSW resulted in significantly greater weight gain and lower glucose tolerance in S-TF and S-TFEX mice. The S-TE mice weighed lower and displayed higher glucose tolerance on low-fat diet compared to S-TF condition. Acute exposure to RSW disrupts molecular functions in a tissue-specific manner, which may precede the metabolic consequences of chronic exposure to RSW. The present study provides evidence that the variable food intake patterns associated with shift work may result in deleterious metabolic outcomes. A short intense voluntary bout of exercise every 24 hours may serve as a behavioral cue for eating behavior.