Chronic mistimed feeding results in renal fibrosis and disrupted circadian blood pressure rhythms

Abstract

Circadian disruption is a disturbance in biological timing which can occur within or between different organizational levels, ranging from molecular rhythms within specific cells to misalignment of behavioral and environmental cycles. Previous work from our group showed that less than one week of food restriction to the light (inactive) period is sufficient to invert diurnal blood pressure rhythms in mice. However, kidney excretory rhythms and functions remained aligned with the light-dark cycle. Shift workers have increased risk of cardiovascular disease that may different between sexes and often have irregular mealtimes making the possibility of mistimed feeding as a potential contributor to the development of kidney disease. Thus, we hypothesized that chronic mistimed food intake would result in adverse cardiorenal effects with sex-differences in severity. Here we show that chronic circadian disruption via mistimed feeding results in renal fibrosis and aortic stiffness in a sex-dependent manner. Our results indicate the importance of meal timing for maintenance of blood pressure rhythms and kidney function, particularly in males. Our results also demonstrate females are better able to acclimate to circadian-related behavioral change.