Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/187166
Title: | Disrupted circadian oscillations in type 2 diabetes are linked to altered rhythmic mitochondrial metabolism in skeletal muscle |
Author: | Gabriel, Brendan M. Altintas, Ali Smith, Jonathon A. B. Sardon-Puig, Laura Zhang, Xiping Basse, Astrid L. Laker, Rhianna C. Gao, Hui Liu, Zhengye Dollet, Lucile Treebak, Jonas T. Zorzano Olarte, Antonio Huo, Zhiguang Rydén, Mikael Lanner, Johanna T. Esser, Karyn A. Barrès, Romain Pillon, Nicolas J. Krook, Anna Zierath, Juleen R. |
Keywords: | Ritmes circadiaris Diabetis Circadian rhythms Diabetes |
Issue Date: | 22-Oct-2021 |
Publisher: | American Association for the Advancement of Science |
Abstract: | Circadian rhythms are generated by an autoregulatory feedback loop of transcriptional activators and repressors. Circadian rhythm disruption contributes to type 2 diabetes (T2D) pathogenesis. We elucidated whether altered circadian rhythmicity of clock genes is associated with metabolic dysfunction in T2D. Transcriptional cycling of core-clock genes BMAL1, CLOCK, and PER3 was altered in skeletal muscle from individuals with T2D, and this was coupled with reduced number and amplitude of cycling genes and disturbed circadian oxygen consumption. Inner mitochondria-associated genes were enriched for rhythmic peaks in normal glucose tolerance, but not T2D, and positively correlated with insulin sensitivity. Chromatin immunoprecipitation sequencing identified CLOCK and BMAL1 binding to inner-mitochondrial genes associated with insulin sensitivity, implicating regulation by the core clock. Inner-mitochondria disruption altered core-clock gene expression and free-radical production, phenomena that were restored by resveratrol treatment. We identify bidirectional communication between mitochondrial function and rhythmic gene expression, processes that are disturbed in diabetes. |
Note: | Reproducció del document publicat a: https://doi.org/10.1126/sciadv.abi9654 |
It is part of: | Science Advances, 2021, vol. 7, num. 43, p. 1-19 |
URI: | http://hdl.handle.net/2445/187166 |
Related resource: | https://doi.org/10.1126/sciadv.abi9654 |
ISSN: | 2375-2548 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
723938.pdf | 3.54 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License