All ETDs from UAB

Advisory Committee Chair

David M Pollock

Advisory Committee Members

Carmen De Miguel

Shannon Bailey

Kelly A Hyndman

Edward W Inscho

Document Type

Dissertation

Date of Award

2023

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 has shown that changing the timing of food availability is sufficient to lower blood pressure and improve insulin sensitivity in prediabetic males, demonstrating the importance of timing of food intake for cardiovascular health. Findings from our group demonstrated that less than one week of mistimed feeding is sufficient to invert diurnal blood pressure rhythms, although kidney excretory rhythms and kidney function remained aligned with the light-dark cycle. Many shift workers maintain a lifestyle of irregular meal timing for years, even decades, and are at greater risk for cardiovascular and kidney disease. However, the long-term role of mistimed feeding in the development of kidney disease is still not known. Here, we show that long-term circadian disruption via food availability results in moderate renal damage in a sex-dependent manner. We found that circadian rhythms in blood pressure are lost as early as four weeks after the start of mistimed food availability in mice. Both male and female mice subjected to this type of circadian disruption developed significant renal cortical fibrosis. Interestingly, males, but not females, also demonstrated fibrosis in the renal outer medulla. Our results demonstrate the integral role of the peripheral clocks in circadian misalignment. Overall, our studies provide new insights into how meal timing impacts risk of kidney fibrosis independent of overall hypertension. Further, we conclude that disrupted diurnal blood pressure rhythmicity is associated with increased kidney disease risk as observed in humans with non-dipping blood pressure patterns. Our studies suggest that females are better protected against changes in food availability.

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