Abstract MP17: Time Restricted Feeding Improves Cardiovascular Rhythms And Vascular Metabolism In Mice On A Chronic High Fat Diet

Abstract

Irregular timing of food intake increases hypertension and cardiometabolic disease risk. A chronic high fat diet (HFD) also disrupts circadian rhythms. We hypothesized that active period time restricted feeding (TRF) during the last 2 weeks in mice on a chronic HFD will improve blood pressure rhythm, diurnal variation of circulating plasma factors, and vascular metabolism. Mice (male 8-week old, C57BL/6J) were fed a normal diet (ND; 10% fat) or HFD (45% fat) for 20 weeks ad libitum. For the final 2 weeks, half of the HFD mice were subjected to TRF. Mean arterial pressure (MAP), heart rate (HR), and locomotor activity were assessed by telemetry. TRF significantly increased the active-inactive period difference in MAP and HR in in mice fed a HFD (ΔMAP: ND: 16±0.7 mmHg, HFD: 15±0.8 mmHg, HFD+TRF: 18±0.9 mmHg, n=6-8, p=0.01; ΔHR: ND: 68±5.1 bpm, HFD: 69±6.5 bpm, HFD+TRF: 113±7.9 bpm, n=6-8, p<0.01). Diurnal changes in locomotor activity are not different between groups. At the end of the study, plasma was collected at 4 hour intervals over a 24 hour period (ZT0 at 7AM; ZT12 at 7PM). Circulating levels of liver-derived mediators β-hydroxybutyrate (βHB) and insulin-like growth factor-1 (IGF-1) showed significant differences due to diet but not TRF (βHB, ZT21: ND: 0.16±0.01 mM, HFD: 0.20±0.02 mM, HFD+TRF: 0.19±0.01 mM, n=5-6, p=0.02; IGF-1, ZT5: ND: 232±18 ng/mL, HFD: 292±34 ng/mL , HFD+TRF: 371±14 ng/mL, n=5-6, p<0.01). Plasma leptin was significantly higher in mice on HFD and reduced by TRF at ZT12 (ND: 5.3±1.3 ng/mL, HFD: 22.5±2.9 ng/mL, HFD+TRF: 10.3±3.5ng/mL, n=5-6, p<0.01) and ZT17 (ND: 6.7±1.1 ng/mL, HFD: 32.5±3.0 ng/mL, HFD+TRF: 25.0±1.3 ng/mL, n=5-6, p<0.01). Plasma adiponectin was unchanged between all groups. TRF in HFD mice increased NAD + , important for metabolism, in renal vessels at ZT17 (HFD: 0.10±0.02 pmol/μg; HFD+TRF: 0.19±0.03 pmol/μg; n=5, p=0.03). Aortic NAD + at ZT1 was not affected by TRF in HFD mice (HFD: 1.83±0.35 pmol/μg, HFD+TRF: 1.35±0.35 pmol/μg, n=4, p=0.37). Our results indicate that TRF in mice on HFD increases the active-inactive period difference in MAP and HR and alters plasma metabolites, suggesting the timing of food intake on a chronic HFD improves cardiovascular rhythms with increased renal vascular metabolism and reduced leptin levels.