Time Restricted Feeding Reverses Western Diet-Induced Disruptions in Diurnal Blood Pressure Rhythms and Aortic Media Thickening

Abstract

Cardiovascular disease is one of the primary contributors to the global burden of disease. A poor diet commonly observed in the western world consisting of elevated fat, salt, and sugar is estimated to contribute to 14% of disability-associated life years and increased mortality. High fat fed animals have altered circadian rhythms and increased aortic and renal damage. As the timing of food intake is critical for establishing and maintaining proper circadian rhythms, and disruption of these rhythms is detrimental to cardiovascular health, we hypothesize that time restricted feeding, similar to intermittent fasting, will rescue western diet-induced cardiovascular disease. In this study, alongside normal diet (ND 10% kcal fat, 0.25% by weight salt. 0.7% kcal sucrose) controls, C57Bl/6J male mice were switched to a high fat (45% kcal), high salt (4% by weight), and high sugar (17% kcal) diet for 20 weeks. At 18 weeks, a portion of the western-diet (WD) mice were subjected to time-restricted feeding (TRF) where access to food was restricted to the active period, 6pm to 6am. A subset of mice were implanted with radiotelemeters 14 weeks into the study to measure 24hr conscious blood pressure. Body weight was measured throughout the study confirming increased weight gain in WD mice compared to ND mice and that TRF did not induce weight loss. By 10 weeks, WD fed animals showed increased pulse wave velocity indicative of vascular remodeling (p<0.05). Remarkably, WD mice exhibited a non-dipping phenotype of their blood pressure. Active blood pressures were similar across groups 137 to 142mmHg; however, WD mice exhibited an elevation in inactive blood pressure (124mmHg) compared to ND mice (108mmHg). TRF returned inactive blood pressure (110mmHg) to ND levels despite being on a WD. The mesor of a cosiner analysis of the diurnal pattern of blood pressure is elevated in WD mice which is rescued by TRF. WD and WD-TRF mice exhibited increased perirenal fat accumulation, serum insulin, renal mass, and albuminuria compared to ND mice. There was no difference between WD and WD-TRF mice in these endpoints. We also observed increased renal inflammation in WD and WD-TRF mice measured by flow cytometric analysis of immune infiltrates, yet no effect of TRF itself. Histological analysis of aortic sections by Masson’s trichrome revealed a significant thickening of the tunica media in WD mice (52.91±1.70μm, n=15) compared to ND mice (47.12±1.88μm, n=14, p<0.05) which was reversed by TRF treatment (44.97±1.22μm, n=14, p<0.01). These results demonstrate that western diet contributes to chronic renal inflammation and aortic remodeling. We present novel findings that TRF rescues WD-induced non-dipping blood pressure and tunica media thickening. AHA-DF837441, NIH-1T32AI138932-01A1, 1R01HL161212-01A1, 19EIA34480023, 19IPLOI34760558, NIH-5T32GM 8111-35, AHA-MRT827566 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.