Differentiating Cellular Osmotic Stress In Healthy Well-hydrated And Under-hydrated Young Adults

Whereas a linkage is evident between hydration practices and chronic health outcomes, viable reported mechanisms and predictive circulating protein biomarkers are limited. Circulating biomarkers of osmotic stress representing tissue level cellular osmotic stress in well- (WH) vs. under-hydrated (UH) individuals could denote allostatic overload and undue negative chronic health risk. PURPOSE: Clarify genomic changes in peripheral blood mononuclear cells (PBMCs) in those who are WH and UH. METHODS: PBMCs from 11 WH and 8 UH healthy, young (21 ± 1y) men (WH n = 3; UH n = 3) and women (WH n = 8; UH n = 5) were obtained from fasted, morning blood samples. RNA was isolated and analyzed for differential expression of 82 osmotic stress genes. Hydration status was assigned by the collective of morning plasma osmolality (Posm: WH = 288 ± 5; UH = 295 ± 5), morning plasma copeptin (Pcop: WH = 4.7 ± 1.6; UH = 11.9 ± 5.3), first morning urine osmolality (FMUosm: WH = 597 ± 218; UH = 971 ± 120), and previous 24 h (24Uosm: WH = 393 ± 148; UH = 891 ± 219) and 5d average Uosm (5dUosm: WH = 408 ± 157; UH = 898 ± 109). ANOVA with Tukey post hoc tests determined significance (p < 0.05). RESULTS: Genes for transcription factor ATF4 and cell adhesion molecule CTGF were upregulated in UH, whereas genes for select channel and transporters (AQP9, MLC1, ABCB1), molecular chaperone HSPA1A, DNA damage and repair/translation regulator MAPK1, apoptosis VEGFA, cell adhesion molecule CCN2, mitogenic TGFA, plasminogen activator PLAT, and transcript factor NFAT5 were downregulated in UH PBMCs. CONCLUSIONS: These data demonstrate differential responses in circulating immune cells stratified by hydration status. Downregulation of specific osmotic stress genes in UH contradicted our assumption that target tissue cells would increase osmotic stress expression in PBMCs. This paradox could be explained by chronic UH downregulating osmotic stress pathways or circulating immune cells possibly being unaffected by or resistant to osmotic stress inherent to other cells/tissues. Further, these biomarkers may not have captured relevant differences in protein translation. Nonetheless, our findings may be instrumental in contributing to profiling chronic health risk related to routine hydration practices. Funding: Drinking Water Research Foundation and University of Hartford.