Circadian phase inversion causes insulin resistance in a rat model of night work and jet lag

Abstract Shift workers have an increased risk to develop type 2 diabetes. We aimed to investigate the underlying mechanisms and the role of the timing of food intake by subjecting rats to an acute phase inversion of the light/dark (L/D) cycle. In the first experiment, with food available ad libitum,...

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Main Authors: Anhui Wang, Ewout Foppen, Valentina S. Rumanova, Tess Kool, Andries Kalsbeek, Dirk J. Stenvers
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-91485-z
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author Anhui Wang
Ewout Foppen
Valentina S. Rumanova
Tess Kool
Andries Kalsbeek
Dirk J. Stenvers
author_facet Anhui Wang
Ewout Foppen
Valentina S. Rumanova
Tess Kool
Andries Kalsbeek
Dirk J. Stenvers
author_sort Anhui Wang
collection DOAJ
description Abstract Shift workers have an increased risk to develop type 2 diabetes. We aimed to investigate the underlying mechanisms and the role of the timing of food intake by subjecting rats to an acute phase inversion of the light/dark (L/D) cycle. In the first experiment, with food available ad libitum, male Wistar rats were implanted with jugular vein catheters and intravenous glucose tolerance tests were performed at either ZT2 or ZT14. Three days after the 12 h phase shift, these glucose tolerance tests were repeated. In the second experiment, rats were housed in metabolic cages for the continuous measurement of multiple behavioral and metabolic parameters after the 12 h phase shift, food was available ad libitum or restricted to the light or dark period. The daily rhythm of glucose tolerance, and the peak and trough corticosterone levels, adapted within three days after exposure to the inverted L/D cycle. However, phase inversion caused insulin resistance at the onset of the active phase. Under ad libitum feeding conditions, the daily rhythms of locomotor activity and energy expenditure adapted faster to the inverted L/D cycle compared to the other behavioral rhythms measured. Food restriction to the dark period facilitated behavioral adaptation to the new circadian phase.
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issn 2045-2322
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spelling doaj-art-baafd47cc08746fa9de097c28e94e1ff2025-08-20T03:05:25ZengNature PortfolioScientific Reports2045-23222025-03-0115111210.1038/s41598-025-91485-zCircadian phase inversion causes insulin resistance in a rat model of night work and jet lagAnhui Wang0Ewout Foppen1Valentina S. Rumanova2Tess Kool3Andries Kalsbeek4Dirk J. Stenvers5Department of Endocrinology and Metabolism, Amsterdam UMC, University of AmsterdamLaboratory of Endocrinology, Department of Laboratory Medicine, Amsterdam UMC, University of AmsterdamDepartment of Endocrinology and Metabolism, Amsterdam UMC, University of AmsterdamDepartment of Endocrinology and Metabolism, Amsterdam UMC, University of AmsterdamDepartment of Endocrinology and Metabolism, Amsterdam UMC, University of AmsterdamDepartment of Endocrinology and Metabolism, Amsterdam UMC, University of AmsterdamAbstract Shift workers have an increased risk to develop type 2 diabetes. We aimed to investigate the underlying mechanisms and the role of the timing of food intake by subjecting rats to an acute phase inversion of the light/dark (L/D) cycle. In the first experiment, with food available ad libitum, male Wistar rats were implanted with jugular vein catheters and intravenous glucose tolerance tests were performed at either ZT2 or ZT14. Three days after the 12 h phase shift, these glucose tolerance tests were repeated. In the second experiment, rats were housed in metabolic cages for the continuous measurement of multiple behavioral and metabolic parameters after the 12 h phase shift, food was available ad libitum or restricted to the light or dark period. The daily rhythm of glucose tolerance, and the peak and trough corticosterone levels, adapted within three days after exposure to the inverted L/D cycle. However, phase inversion caused insulin resistance at the onset of the active phase. Under ad libitum feeding conditions, the daily rhythms of locomotor activity and energy expenditure adapted faster to the inverted L/D cycle compared to the other behavioral rhythms measured. Food restriction to the dark period facilitated behavioral adaptation to the new circadian phase.https://doi.org/10.1038/s41598-025-91485-zCircadian rhythmDaily rhythmsPhase-shiftDesynchronizationShift workMetabolism
spellingShingle Anhui Wang
Ewout Foppen
Valentina S. Rumanova
Tess Kool
Andries Kalsbeek
Dirk J. Stenvers
Circadian phase inversion causes insulin resistance in a rat model of night work and jet lag
Scientific Reports
Circadian rhythm
Daily rhythms
Phase-shift
Desynchronization
Shift work
Metabolism
title Circadian phase inversion causes insulin resistance in a rat model of night work and jet lag
title_full Circadian phase inversion causes insulin resistance in a rat model of night work and jet lag
title_fullStr Circadian phase inversion causes insulin resistance in a rat model of night work and jet lag
title_full_unstemmed Circadian phase inversion causes insulin resistance in a rat model of night work and jet lag
title_short Circadian phase inversion causes insulin resistance in a rat model of night work and jet lag
title_sort circadian phase inversion causes insulin resistance in a rat model of night work and jet lag
topic Circadian rhythm
Daily rhythms
Phase-shift
Desynchronization
Shift work
Metabolism
url https://doi.org/10.1038/s41598-025-91485-z
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