Abstract 2110: Fasting-refeeding Dynamics Induce Distinct Vascular Responses in Lean and Obese Mice

Background: Intermittent fasting (IF) can improve arterial stiffness, a predictor of cardiovascular disease. However, it is still unclear how many bouts of IF are needed to improve arterial stiffness, and once improvements occur, how long after the fasting period are they maintained. Thus, the primary purpose of this study was to determine how long changes in arterial stiffness are maintained after IF and how many IF cycles are required to alter arterial stiffness in lean and obese animals. Methods: Wild-type (WT) and genetically obese (Ob) mice were randomized to an 11-week protocol to receive either ad libitum control diet (Ad-Lib) or a once weekly 24 hr fast (IF), yielding 4 groups: WT+Ad-Lib; WT+IF; Ob+Ad-Lib; and Ob+IF. Body weight was measured weekly while arterial pulse wave velocity (aPWV) was measured at baseline and at least 24 hrs after fasting at mid- (weeks 5-6), and endpoints (weeks 9-10). To test the persistence of de-stiffening after one week of IF, IF groups were further split only during week 1 of the protocol such that body weight and aPWV were measured immediately after the first 24 hr fast, 1 day after refeeding, or 7 days after refeeding. Results: In WT mice, body weight was reduced by the 24 hr fast (p<0.01) but rebounded after a day of refeeding (p=0.22) when compared to baseline. Interestingly, aPWV was increased after the 24 hr fast (p=0.02) but was restored back to baseline levels within 24 hrs and did not change thereafter. In Ob animals, no significant differences in body weight were found between baseline and any timepoint during the first week. However, compared to baseline, Ob+IF mice had reduced body weight (p<0.01) and aPWV (p<0.01) at the midpoint, and modestly reduced aPWV at the endpoint (p=0.06). Conclusions: A single 24 hr fast increased aPWV in WT mice yet these acute changes returned to baseline within 24 hours of refeeding and did not change thereafter. A single 24 hr fast did not affect aPWV in Ob mice, whereas 5 weeks of IF ameliorated body weight and aPWV, with these vascular improvements being maintained with continued IF for at least another 5 weeks. These data suggest that once weekly 24 hr IF could be a viable dietary strategy to attenuate obesity-induced arterial stiffness.