Abstract P282: Time Restricted Feeding In Mice On A Chronic High Fat Diet Leads To Reduced Aortic Damage And Oxidative Stress

Abstract

Diet-induced obesity is associated with an increased risk of developing cardiovascular disease (CVD) . Aortic damage and stiffness are critical risk factors for CVD progression, especially with chronic high fat diet (HFD). Mice fed HFD ad libitum have increased food intake during the inactive period. We previously showed that HFD leads to significantly reduced blood pressure (BP) dipping and that time restricted food availability to the active period (TRF) in the final 2 weeks of HFD restores BP dipping. Thus, we hypothesized that TRF will reduce aortic damage and stiffness in chronic HFD mice. Utilizing this same mouse model of ad libitum chronic HFD (20 weeks 45% fat diet, male C57Bl6/J mice) compared to normal fat diet (NFD, 10% fat) and TRF intervention (food during lights off active period only from weeks 18-20), we determined aortic fibrosis and stiffness. By histological staining and quantitative analysis of the fibrosis area, HFD+TRF mice had significantly reduced fibrosis compared to HFD mice (% fibrosis per area, NFD: 143, NFD+TRF: 132, HFD: 175, HFD+TRF: 105, 2-way ANOVA, TRF effect: p=0.02). Aortic stiffness was measured by pulse wave velocity (PWV, Vevo 3100). We found that HFD fed mice have a significant increase in PWV compared to NFD group with no significant difference in the HFD+TRF and NFD+TRF groups compared to the NFD group (PWV m/sec, NFD: 1.60, NFD+TRF: 1.5, HFD: 2.30, HFD+TRF: 1.70, 2-way ANOVA, diet effect: p=0.02). We further analyzed plasma sE-selectin (endothelial-specific damage marker) and 8-isoprostane (oxidative stress marker) in HFD and HFD+TRF mice. Plasma from HFD+TRF mice showed significantly reduced sE-selectin and 8-isoprostane compared to HFD mice (sE-selectin ng/ml, HFD: 3.50, HFD+TRF: 1.85, p=0.027; 8-isoprostane ng/ml, HFD: 159.1, HFD+TRF: 59.6, p=0.008). Thus, TRF in chronic HFD mice leads to reduced endothelial injury and oxidative stress that is correlated with reduced aortic fibrosis and stiffness compared to ad libitum HFD mice. This study highlights that restricting the time of food intake in a model of diet-induced obesity minimizes CVD risk by reducing aortic damage and oxidative stress.