| Title: | Sexual dimorphism in the response to chronic circadian misalignment on a high-fat diet |
| Journal: | Science Translational Medicine |
| Published: | 17 May 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37196066/ |
| DOI: | https://doi.org/10.1126/scitranslmed.abo2022 |
| Citations: | 15 (15 in last 2 years) as of 8 Aug 2024 |
Publication 11453
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Longitudinal studies associate shiftwork with cardiometabolic disorders but do not establish causation or elucidate mechanisms of disease. We developed a mouse model based on shiftwork schedules to study circadian misalignment in both sexes. Behavioral and transcriptional rhythmicity were preserved in female mice despite exposure to misalignment. Females were protected from the cardiometabolic impact of circadian misalignment on a high-fat diet seen in males. The liver transcriptome and proteome revealed discordant pathway perturbations between the sexes. Tissue-level changes were accompanied by gut microbiome dysbiosis only in male mice, biasing toward increased potential for diabetogenic branched chain amino acid production. Antibiotic ablation of the gut microbiota diminished the impact of misalignment. In the United Kingdom Biobank, females showed stronger circadian rhythmicity in activity and a lower incidence of metabolic syndrome than males among job-matched shiftworkers. Thus, we show that female mice are more resilient than males to chronic circadian misalignment and that these differences are conserved in humans.</p>
14 Authors
- Seán T Anderson
- Hu Meng
- Thomas G Brooks
- Soon Yew Tang
- Ronan Lordan
- Arjun Sengupta
- Soumyashant Nayak
- Antonijo Mřela
- Dimitra Sarantopoulou
- Nicholas F Lahens
- Aalim Weljie
- Gregory R Grant
- Frederic D Bushman
- Garret A FitzGerald
Enabling scientific discoveries that improve human health