In mammals a network of circadian clocks coordinates behavior and physiology with 24-h environmental cycles. Consumption of high-fat diet disrupts this temporal coordination by advancing the phase of the liver molecular clock and altering daily rhythms of eating behavior and locomotor activity. In this study we sought to determine whether these effects of high-fat diet on circadian rhythms were reversible. We chronically fed mice high-fat diet and then returned them to low-fat chow diet. We found that the phase of the liver PERIOD2::LUCIFERASE rhythm was advanced (by 4h) and the daily rhythms of eating behavior and locomotor activity were altered for the duration of chronic high-fat diet feeding. Upon diet reversal, the eating behavior rhythm was rapidly reversed (within 2 days) and the phase of the liver clock was restored by 7 days of diet reversal. In contrast, the daily pattern of locomotor activity was not restored even after 2 weeks of diet reversal. Thus, while the circadian system is sensitive to changes in the macronutrient composition of food, the eating behavior rhythm and liver circadian clock are specifically tuned to respond to changes in diet.

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Published in PLOS One, v. 10, no. 9, article e0137970, p. 1-12.

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

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This research was supported by National Institutes of Health (www.nih.gov) grants DK098321 (to J.S.P.) and DK058404 (Pilot Award to J.S.P.). J.S.P. was supported by a Young Investigator Award from the Vanderbilt University Digestive Disease Research Center (National Institutes of Health grant P30 DK058404). K.D.N. was supported by resources of the VA Tennessee Valley Healthcare System and National Institutes of Health grants (DK085712 and DK064857) and the Diabetes Research and Training Center (DK20593). The authors declare no competing financial or non-financial interests. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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S1 Fig. Effects of high-fat diet and diet reversal on liver bioluminescence rhythms.

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S2 Fig. The high-fat diet-induced advance of the liver PER2::LUC rhythm is not an artifact of the culture procedure.

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S3 Fig. Daily distribution of eating behavior during chow, chronic high-fat diet consumption, and diet reversal.

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S4 Fig. Daily rhythms of eating behavior during chronic high-fat diet consumption.

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S5 Fig. Eating behavior during diet reversal.

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S6 Fig. Circular histograms of daily eating behavior during diet reversal.

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S7 Fig. Locomotor activity rhythms during chronic high-fat diet consumption and diet reversal.

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S8 Fig. Daily rhythms of locomotor activity during chronic high-fat diet consumption.

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S9 Fig. Daily distribution of locomotor activity during chow, chronic high-fat diet consumption, and diet reversal.

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S10 Fig. Daily rhythms of locomotor activity during diet reversal.

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S1 File. Body weight and liver phase data.

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S2 File. Eating behavior raw data.

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S3 File. ARRIVE Guidelines checklist.

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S1 Table. Vector properties of locomotor activity rhythms in individual mice during diet reversal.

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