Lack of food intake during shift work alters the heart transcriptome and leads to cardiac fibrosis and inflammation in rats

Many epidemiological studies revealed that shift work is associated with increased risk of cardiovascular diseases. However, the underlying mechanisms remain poorly understood. An experimental model of shift work in rats has been shown to recapitulate the metabolic disorders observed in human shift workers, and used to demonstrate that restricting food consumption outside working hours prevents shift work-associated obesity and metabolic disturbance. Here we used this model to characterize the effects of shift work in the heart. We show that experimental shift work reprograms the heart cycling transcriptome independently of food consumption. While phases of rhythmic gene expression are distributed across the 24-hour day in control rats, they are clustered towards discrete times in shift workers. Additionally, preventing food intake during shift work affects the expression level of hundreds of genes in the heart. Many of them are found in transcriptional signatures associated with pressure overload and cardiac hypertrophy, and encode for components of the extracellular matrix and inflammatory markers. Consistent with this, the heart of shift worker rats not eating during work exhibits fibrosis and is colonized by immune cells. While maintaining food access during shift work has less effects on gene expression, genes found in transcriptional signatures of cardiac hypertrophy remain affected, and the heart of shift worker rats exhibits fibrosis without inflammation. Together, our findings provide insights into how shift work affects cardiac function, and suggest that some interventions aiming at mitigating metabolic disorders in shift workers may have adverse effects on cardiovascular diseases. ### Competing Interest Statement The authors have declared no competing interest.