Abstract 111: Active Time-Restricted Feeding Potently Protects Blood Pressure Daily Rhythm in Diabetic Mice
Abstract
Diabetes is associated with high prevalence of non-dipping blood pressure (BP), which is the most common form of disruption in BP daily rhythm. Non-dipping BP is emerging as an independent risk factor of cardiovascular diseases and target organ damages. A large body of human and animal evidence demonstrated that active-phase time-restricted feeding (ATRF) is highly metabolic beneficial. However, the effects of ATRF on BP daily rhythm are unknown. The current study investigates whether, and how ATRF protects mice from non-dipping BP in a type 2 diabetic db/db mouse model. The results demonstrated that ATRF potently prevented the disruption, as well as restored the already disrupted BP daily rhythm in db/db mice (BP oscillation amplitude (mmHg): ad libitum feeding (ALF) vs. ATRF: 4.95±0.83 vs. 12.74±1.22, p<0.001). The loss of BP dipping in db/db mice was associated with an increased portion of daily food intake during the inactive light-phase, which preceded the development of non-dipping BP (light-phase food intake (g): control vs. db/db: 0.33±0.19 vs. 3.38±0.07, p<0.0001). Moreover, feeding normal mice at the wrong time with inactive-phase time-restricted feeding (ITRF) compromised BP daily rhythm (BP oscillation amplitude (mmHg): ALF vs. ITRF: 7.69±0.44 vs. 4.59±0.44, p<0.01), suggesting the time of feeding plays an important role in BP daily rhythm. While multiple mechanisms likely contribute to the powerful protection of ATRF on BP daily rhythm in db/db mice, we found that improved autonomic nervous system mediates, at least in part, the protective effects of ATRF. At the molecular level, we found that among the multiple clock genes examined, the mRNA oscillation of Bmal1, an obligatory key core clock gene, was disrupted in diabetes and restored by ATRF in multiple peripheral tissues in db/db mice. Using inducible global Bmal1 knockout mice, we further demonstrated that Bmal1 was partially required for ATRF to protect the BP daily rhythm. Taken together, our results revealed that ATRF potently protects BP daily rhythm in diabetic db/db mice in part by modulating autonomic nervous system and clock gene Bmal1. These novel findings suggest ATRF may serve as a novel and effective chronotherapy against the disruption of BP daily rhythm in diabetes.
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© 2019 by American Heart Association, Inc.
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Published in print: September 2019
Published online: 4 September 2019
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