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Christie, S., Vincent, A. D., Li, H., Frisby, C. L., Kentish, S. J., O'Rielly, R., et al. (2018). A rotating light cycle promotes weight gain and hepatic lipid storage in mice. Am J Physiol Gastrointest Liver Physiol, in press.
Abstract: Processes involved in regulation of energy balance and intermediary metabolism are aligned to the light-dark cycle. Shift-work and high fat diet (HFD)-induced obesity disrupt circadian rhythmicity and are associated with increased risk of non-alcoholic fatty liver disease (NAFLD). This study aimed to determine the effect of simulating shift work on hepatic lipid accumulation in lean and HFD-mice. C57BL/6 mice fed a standard laboratory diet (SLD) or HFD for 4wks were further allocated to a normal light (NL)-cycle (lights on:0600-1800hr) or rotating light (RL)-cycle (3-days NL and 4-days reversed (lights on:1800-0600hr) repeated) for 8wks. Tissue was collected every 3hrs beginning at 0600hr. HFD-mice gained more weight than SLD-mice, and RL-mice gained more weight than NL-mice. SLD-NL and HFD-NL mice, but not RL-mice, were more active, had higher respiratory quotients and consumed/expended more energy during the dark phase compared to the light phase. Blood glucose and plasma cholesterol and triglyceride concentrations were elevated in HFD and SLD-RL compared to SLD-NL mice. Hepatic glycogen was elevated in HFD compared to SLD-mice. Hepatic triglycerides were elevated in SLD-RL and HFD-mice compared to SLD-NL. Circadian rhythmicity of hepatic acetyl-CoA carboxylase (ACACA) mRNA was phase shifted in SLD-RL and HFD-NL and lost in HFD-RL mice. Hepatic ACACA protein was reduced in SLD-RL and HFD-mice compared to SLD-NL mice. Hepatic adipose triglyceride lipase was elevated in HFD-NL compared to SLD-NL but lower in RL-mice compared to NL-mice irrespective of diet. -Conclusion: A RL-cycle model of shift-work promotes weight gain and hepatic lipid storage even in lean conditions.