GSE124870
Molecular characterization of the effects of shift work and food consumption on cardiovascular disease in the rat
Shift work misaligns the circadian clock and leads to an increased risk of cancer, cardiovascular diseases, and metabolic disorders. Furthermore, food consumed during the rest phase is a major contributor to this misalignment, as food access restricted to the endogenous active phase, at night, prevents against the adverse effects of shift work on obesity and diabetes in rats. In this study, we aimed to investigate the molecular mechanisms by which shift work and food consumption contribute to an increased risk of cardiovascular disorders. To this end, we used a model of shift work in rats, whereby animals are exposed to a 12:12 light:dark cycle and are forced to be active for eight-hours during their natural rest phase during the day, Monday to Friday for five consecutive weeks. Given the preventive effects of temporal restriction of food intake, a group of shift worker rats with food access restricted to the night was included in addition to controls and shift workers. To gain insight into the molecular underpinnings of shift-work associated cardiovascular pathologies, we performed RNA-Seq analysis and Picrosirius Red staining in rat hearts. Our results show that shift work in rats, regardless of the time of food consumption, have an increase in collagen deposition in the heart. In addition, the expression of many genes encoding key fibrotic pathways was found to be up-regulated in shift worker rats that had their food restricted to the active phase. Altogether, our results suggest that five weeks of shift work in rats is capable of inducing cardiovascular disease through an up-regulation of collagen deposition in the heart. Overall design: mRNA sequencing on rat hearts under 3 different shiftwork paradigms at 6 timepoints in triplicate