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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 4

TRF reduces measures of kidney damage to the kidney medullary vasa recta area in HFD mice.

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TRF reduces measures of kidney damage to the kidney medullary vasa recta...
Representative histological images, quantitative histological scoring of kidney damage, medullary fibronectin gene expression, and representative immunohistochemical images and quantitative analyses of kidney immune cells in ND, ND+TRF, HFD, and HFD+TRF mice. Representative images and scoring of kidney medullary vasa recta region sections. (A) Masson’s trichrome staining, (B) fibrosis histological scores, (C) Picrosirius red staining under polarized light, (D) quantitation of collagen I and III content, (E) Picrosirius red staining under brightfield light. Arrows indicate vasa recta fibrosis in A and E. (F) Kidney medullary fibronectin mRNA expression. Representative images of medullary vasa recta region with immunohistochemical staining for (G) CD3+ cells and (I) immunohistochemical staining for F4/80+ cells. Scale bar = 50 μm. Brown staining indicates CD3+ cells and F4/80+ cells. Quantitative analysis of (H) CD3+ cells per medullary vasa recta bed and (J) F4/80+ cells per medullary vasa recta bed. Scale bar = 50 μm. Two-way ANOVA was used to compare diet and time of feeding with Tukey’s post hoc test for histological scoring assessments (n = 5–13, *P < 0.05).

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