Molecular choreography to acute heat exposure in a simulated extreme high temperature environment

Abstract Occupational exposure to extreme high temperature and increasing global temperatures require enhanced understanding of how heat exposure impacts human health. However, the molecular changes underlying the response to heat exposure in humans remain to be elucidated. This study used longitudinal multi-omics profiling to assess the impact of acute heat exposure (50℃ for 30 min) in 24 subjects from a mine rescue team. Intravenous blood samples were collected before acute heat exposure (baseline) and at 5 min, 30 min, 1 h, and 24 h after acute heat exposure (recovery). In-depth multi-omics profiling was performed on each sample, including plasma proteomics (untargeted), metabolomics (untargeted), and gene expression (transcriptomics) of peripheral blood monocytes and neutrophils. After data curation and annotation, the final dataset contained 5616 analytes, including 478 proteins, 1995 metabolites, and 3143 transcripts. Time-series analysis unveiled an orchestrated molecular choreography of changes involving the immune response, coagulation, acid-base balance, oxidative stress, cytoskeleton and energy metabolism. Further analysis through protein-protein interactions and network analysis revealed potential regulators of acute heat exposure. Moreover, novel blood-based analytes that predicted change in cardiopulmonary function after acute heat exposure were identified. This study provides a comprehensive evaluation of the molecular changes that underlie the complex physiological processes that occur in humans who undergo heat exposure. Findings will help health impact assessment of extreme high temperature and inform future mechanistic and clinical studies.