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Time-restricted feeding reduces cardiovascular disease risk in obese mice
Paramita Pati, Carmen De Miguel, Jodi R. Paul, Dingguo Zhang, Jackson Colson, John Miller Allan, Claudia J. Edell, Megan K. Rhoads, Luke S. Dunaway, Sara N. Biswal, Yihan Zhong, Randee Sedaka, Telisha Millender-Swain, Shannon M. Bailey, Karen L. Gamble, David M. Pollock, Jennifer S. Pollock
Paramita Pati, Carmen De Miguel, Jodi R. Paul, Dingguo Zhang, Jackson Colson, John Miller Allan, Claudia J. Edell, Megan K. Rhoads, Luke S. Dunaway, Sara N. Biswal, Yihan Zhong, Randee Sedaka, Telisha Millender-Swain, Shannon M. Bailey, Karen L. Gamble, David M. Pollock, Jennifer S. Pollock
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Research Article Nephrology

Time-restricted feeding reduces cardiovascular disease risk in obese mice

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Abstract

Disrupted feeding and fasting cycles as well as chronic high-fat diet–induced (HFD-induced) obesity are associated with cardiovascular disease risk factors. We designed studies that determined whether 2 weeks of time-restricted feeding (TRF) intervention in mice fed a chronic HFD would reduce cardiovascular disease risk factors. Mice were fed a normal diet (ND; 10% fat) ad libitum or HFD (45% fat) for 18 weeks ad libitum to establish diet-induced obesity. ND or HFD mice were continued on ad libitum diet or subjected to TRF (limiting food availability to 12 hours only during the dark phase) during the final 2 weeks of the feeding protocol. TRF improved whole-body metabolic diurnal rhythms without a change in body weight. HFD mice showed reduced blood pressure dipping compared with ND, which was restored by TRF. Further, TRF reduced aortic wall thickness, decreased aortic stiffness, as well as increased kidney tubular brush border integrity, decreased renal medullary fibrosis, and reduced renal medullary T cell inflammation in HFD mice. These findings indicate that TRF may be an effective intervention for improving vascular and kidney health in a model of established diet-induced obesity.

Authors

Paramita Pati, Carmen De Miguel, Jodi R. Paul, Dingguo Zhang, Jackson Colson, John Miller Allan, Claudia J. Edell, Megan K. Rhoads, Luke S. Dunaway, Sara N. Biswal, Yihan Zhong, Randee Sedaka, Telisha Millender-Swain, Shannon M. Bailey, Karen L. Gamble, David M. Pollock, Jennifer S. Pollock

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Figure 2

TRF improves light-phase BP and heart rate changes.

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TRF improves light-phase BP and heart rate changes.
Radiotelemetry was u...
Radiotelemetry was used to measure BP, heart rate (HR), and locomotor activity continuously in unrestrained, conscious mice. Light and dark phases are indicated by white and gray shading, respectively. Telemetry traces of the last 3 days’ average of (A) mean arterial pressure (MAP), (C) systolic blood pressure (SBP), (E) diastolic blood pressure (DBP), (G) HR, and (I) locomotor activity are shown. Individual mouse BP, HR, and activity for the light and dark phase were assessed by calculating the average from ZT3–ZT10 and ZT15–ZT22 periods, as well as the difference between these periods. Eight-hour averages of light and dark phases with main effects and interactions are shown in B, D, F, H, and J. Two-way ANOVA was used to compare diet and time of feeding during the light or dark period (*P < 0.05 ad lib vs. TRF). Three-way repeated measures ANOVA was used to compare diet, time of feeding, and time of day (n = 6–8, *P < 0.05). (K) Representative actograms of locomotor activity generated with ClockLab (Actimetrics) are shown. Bracket indicates the 3 days used for analysis in A–J and L. (L) Food anticipatory activity was assessed from telemetry activity data using activity occurring from ZT8–ZT12 (as percentage of total daily activity). Two-way ANOVA was used to compare diet and time of feeding (n = 6–8, *P < 0.05).

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