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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 1

TRF institutes whole-body metabolic rhythms independent of weight gain.

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TRF institutes whole-body metabolic rhythms independent of weight gain.
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(A) Experimental design of the dietary protocol depicts 18 weeks of ad libitum feeding followed by 2 weeks of ad libitum food availability or TRF. ZT, Zeitgeber time. (B) Longitudinal body weight gain from week 1 to week 18 of ND and HFD followed by week 19 and week 20 of ND (n = 35), ND+TRF (n = 35), HFD (n = 36), and HFD+TRF (n = 36) mice maintained in home cages. (C) Change in body weight from week 18 to week 20 from mice maintained in home cages (*P < 0.05, 2-way ANOVA). (D) Body weights at week 20 in mice maintained in home cages (*P < 0.05, 2-way ANOVA was used to compare diet and time of feeding). Quantitative magnetic resonance (QMR) measurements of (E) fat mass and (F) lean mass (2-way ANOVA was used to compare diet and time of feeding, n = 6, *P < 0.05). Food intake was measured during light and dark phases in metabolic cages. Food intake in g/12 h (G) and in kcal/12 h (H) measured at ZT0 and ZT12. Three-way repeated measures ANOVA was used to compare diet, time of feeding, and time of day (n = 11–12, *P < 0.05). Whole-body metabolic rhythms were measured by Comprehensive Lab Animal Monitoring System (CLAMS) in a separate cohort of mice. Data are shown as the 24-hour average profile of (I) respiratory exchange ratio (RER) and (J) RER light and dark phase differences. (K) Energy expenditure (EE) was determined relative to lean body mass in light and dark phases. Three-way repeated measures ANOVA was used to compare diet, time of feeding, and time of day (n = 6, *P < 0.05). (L) Resting metabolic rate (RMR) was calculated. Two-way ANCOVA with lean body mass as the covariate was used (n = 6, *P < 0.05).

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