Metabolic profiling of night shift work – The HORMONIT study

ABSTRACT

Mechanistic studies are needed to understand how rotating shift work perturbs metabolic processing. We collected plasma samples (n = 196) from 49 males, rotating car factory shift workers at the beginning and end of a night-shift (22:00–06:00 h) and day-shift (06:00 h-14:00 h). Samples underwent targeted LC-MS/MS metabolomics and concentrations of 130 metabolites were log₂-transformed and pareto-scaled. An elastic net selected the most influential metabolites for linear mixed models examining within-person variation in metabolite levels at night-shift end (06:00 h) compared to day-shift start (06:00 h). Quantitative enrichment analysis explored differentially enriched biological pathways between sample time points. We included 20 metabolites (amino acids, biogenic amines, acylcarnitines, glycerophospholipids) in mixed models. Night-shift was associated with changes in concentrations of arginine (geometric mean ratio [GMR] 2.30, 95%CI 1.25, 4.23), glutamine (GMR 2.22, 95%CI 1.53, 3.24), kynurenine (GMR 3.22, 95%CI 1.05, 9.87), lysoPC18:2 (GMR 1.86, 95%CI 1.11, 3.11), lysoPC20:3 (GMR 2.48, 95%CI 1.05, 5.83), PCaa34:2 (GMR 2.27, 95%CI 1.16, 4.44), and PCae38:5 (GMR 1.66, 95%CI 1.02, 2.68). Tryptophan metabolism, glutathione metabolism, alanine metabolism, glycine and serine metabolism, and urea cycle were pathways differing between shifts. Night shift work was associated with changes in metabolites and the perturbation of metabolic and biochemical pathways related to a variety of health outcomes.

KEYWORDS:

• Circadian
• rotating shift work
• shift worker
• metabolomics
• metabolism
• occupational health

Acknowledgements

The authors thank Emilia Molinero, Mayte Martín Bustamante and Elena Juanola Pages from the Generalitat de Catalunya for all of their support in planning this study. The authors also thank Ms. Holly-May Lewis and the Metabolomics Core Facility at the University of Surrey. In addition, the authors thank the study participants for their important contributions.

Disclosure statement

JMN, PS and AT work at the Occupational Health service of the car factory, which was the setting of the present study. Within the HORMONIT study working group they express their own views and do not represent the company. All other authors have no disclosures.

Data availability statement

The data underlying this analysis is available at: https://github.com/bakermarissa/HORMONIT

Additional information

Funding

The study was partially supported by the Instituto de Salud Carlos III-FEDER [PI14/00444]. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program [CEX2018-000806-S], and support from the Generalitat de Catalunya through the CERCA Program.