Time-Restricted Feeding Reinforces Gut Rhythmicity by Restoring Rhythms in Intestinal Metabolism in a Jetlag Mouse ModelSummary
Background & Aims: Circadian disturbances result in adverse health effects, including gastrointestinal symptoms. We investigated which physiological pathways in jejunal mucosa were disrupted during chronic jetlag and prevented during time-restricted feeding (TRF). Enteroids from Bmal1+/+ and...
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Elsevier
2025-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X24001954 |
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| author | Hui Leng Theo Thijs Louis Desmet Guillaume Vanotti Mona Farhadipour Inge Depoortere |
| author_facet | Hui Leng Theo Thijs Louis Desmet Guillaume Vanotti Mona Farhadipour Inge Depoortere |
| author_sort | Hui Leng |
| collection | DOAJ |
| description | Background & Aims: Circadian disturbances result in adverse health effects, including gastrointestinal symptoms. We investigated which physiological pathways in jejunal mucosa were disrupted during chronic jetlag and prevented during time-restricted feeding (TRF). Enteroids from Bmal1+/+ and Bmal1-/- mice were used to replicate the processes that were affected by chronic jetlag and rescued by TRF. Methods: C57BL/6J male mice were subjected to chronic jetlag or night-TRF for 4 weeks. An around-the-clock bulk-RNA sequencing study was performed on the jejunal mucosa. Bmal1+/+ and Bmal1-/- mouse enteroids were generated to study the jejunal epithelial clock dependency of rhythmic jejunal processes. Results: Chronic jetlag disrupted the rhythmicity of jejunal clock genes and the jejunal transcriptome, which was partially rescued by TRF. Genes whose rhythm was altered by chronic jetlag but prevented by TRF were primarily associated with nutrient transport, lipid metabolism, ketogenesis, and cellular organization. In vivo, chronic jetlag caused a phase shift in the rhythmic accumulation of neutral lipids and induced a diurnal rhythm in the number of crypt epithelial cells, both of which were prevented by TRF. In vitro, enteroids replicated the in vivo rhythmic accumulation of neutral lipids in a clock-dependent manner, whereas the rhythm of S phase proliferation was ultradian in both genotypes of enteroids. Conclusions: This pioneering transcriptomic study demonstrates that TRF acts as a robust entrainer during chronic jetlag, realigning disturbances in the circadian clock and the transcriptome involved in metabolic functions in the jejunal mucosa. Enteroids can replicate the rhythmic accumulation of neutral lipids dependent on the jejunal epithelial clock, enabling these functions to be studied in vitro. |
| format | Article |
| id | doaj-art-6ff8ce81de654662bf7328d9c5f52e44 |
| institution | Kabale University |
| issn | 2352-345X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj-art-6ff8ce81de654662bf7328d9c5f52e442025-01-31T05:11:52ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2025-01-01194101440Time-Restricted Feeding Reinforces Gut Rhythmicity by Restoring Rhythms in Intestinal Metabolism in a Jetlag Mouse ModelSummaryHui Leng0Theo Thijs1Louis Desmet2Guillaume Vanotti3Mona Farhadipour4Inge Depoortere5Translational Research Center in Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, BelgiumTranslational Research Center in Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, BelgiumTranslational Research Center in Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, BelgiumTranslational Research Center in Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, BelgiumTranslational Research Center in Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, BelgiumCorrespondence Address correspondence to: Inge Depoortere, PhD, Translational Research Center in Gastrointestinal Disorders (TARGID), Gasthuisberg O&N1, Box 701, 3000 Leuven, Belgium.; Translational Research Center in Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, BelgiumBackground & Aims: Circadian disturbances result in adverse health effects, including gastrointestinal symptoms. We investigated which physiological pathways in jejunal mucosa were disrupted during chronic jetlag and prevented during time-restricted feeding (TRF). Enteroids from Bmal1+/+ and Bmal1-/- mice were used to replicate the processes that were affected by chronic jetlag and rescued by TRF. Methods: C57BL/6J male mice were subjected to chronic jetlag or night-TRF for 4 weeks. An around-the-clock bulk-RNA sequencing study was performed on the jejunal mucosa. Bmal1+/+ and Bmal1-/- mouse enteroids were generated to study the jejunal epithelial clock dependency of rhythmic jejunal processes. Results: Chronic jetlag disrupted the rhythmicity of jejunal clock genes and the jejunal transcriptome, which was partially rescued by TRF. Genes whose rhythm was altered by chronic jetlag but prevented by TRF were primarily associated with nutrient transport, lipid metabolism, ketogenesis, and cellular organization. In vivo, chronic jetlag caused a phase shift in the rhythmic accumulation of neutral lipids and induced a diurnal rhythm in the number of crypt epithelial cells, both of which were prevented by TRF. In vitro, enteroids replicated the in vivo rhythmic accumulation of neutral lipids in a clock-dependent manner, whereas the rhythm of S phase proliferation was ultradian in both genotypes of enteroids. Conclusions: This pioneering transcriptomic study demonstrates that TRF acts as a robust entrainer during chronic jetlag, realigning disturbances in the circadian clock and the transcriptome involved in metabolic functions in the jejunal mucosa. Enteroids can replicate the rhythmic accumulation of neutral lipids dependent on the jejunal epithelial clock, enabling these functions to be studied in vitro.http://www.sciencedirect.com/science/article/pii/S2352345X24001954Circadian RhythmsChronic JetlagTime-Restricted FeedingJejunal MetabolismMouse Enteroid |
| spellingShingle | Hui Leng Theo Thijs Louis Desmet Guillaume Vanotti Mona Farhadipour Inge Depoortere Time-Restricted Feeding Reinforces Gut Rhythmicity by Restoring Rhythms in Intestinal Metabolism in a Jetlag Mouse ModelSummary Cellular and Molecular Gastroenterology and Hepatology Circadian Rhythms Chronic Jetlag Time-Restricted Feeding Jejunal Metabolism Mouse Enteroid |
| title | Time-Restricted Feeding Reinforces Gut Rhythmicity by Restoring Rhythms in Intestinal Metabolism in a Jetlag Mouse ModelSummary |
| title_full | Time-Restricted Feeding Reinforces Gut Rhythmicity by Restoring Rhythms in Intestinal Metabolism in a Jetlag Mouse ModelSummary |
| title_fullStr | Time-Restricted Feeding Reinforces Gut Rhythmicity by Restoring Rhythms in Intestinal Metabolism in a Jetlag Mouse ModelSummary |
| title_full_unstemmed | Time-Restricted Feeding Reinforces Gut Rhythmicity by Restoring Rhythms in Intestinal Metabolism in a Jetlag Mouse ModelSummary |
| title_short | Time-Restricted Feeding Reinforces Gut Rhythmicity by Restoring Rhythms in Intestinal Metabolism in a Jetlag Mouse ModelSummary |
| title_sort | time restricted feeding reinforces gut rhythmicity by restoring rhythms in intestinal metabolism in a jetlag mouse modelsummary |
| topic | Circadian Rhythms Chronic Jetlag Time-Restricted Feeding Jejunal Metabolism Mouse Enteroid |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X24001954 |
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