Abstract P3027: Intermittent Fasting Improves High Fat Diet Mediated Heart Failure With Preserved Ejection Fraction

Intermittent fasting (IF) has improved metabolic aberrations in metabolic diseases, however, the mechanism is unclear. Our lab focuses on 4-hydroxy-2-nonenal (4HNE), an oxidative stress byproduct which accumulates in metabolic diseases, in cardiac damage and activity of aldehyde dehydrogenase 2 (ALDH2), a 4HNE detoxifying enzyme, which was implicated in cardioprotection. We reported that the ALDH2*2 knock-in mutant mice (AL) with low intrinsic ALDH2 activity that were fed with high-fat diet (HFD) exhibited severe heart failure with preserved ejection fraction (HFpEF) compared to HFD fed control mice (C57). We hypothesized that IF can contribute to the improvement of HFpEF even in AL mice by reducing 4HNE. C57 and AL mice that were fed HFD and L-NAME (nitric oxide inhibitor) in drinking water were grouped as C57-free and AL-free meaning taking food freely or C57-IF and AL-IF meaning daily 16 hours fasting with 8-hr free access to food. After 2-months of HFD feeding, the body weights of C57-IF (35.5±3.8g) and AL-IF (36.7±3.4g) groups were significantly lower than C57-free (43.5±4.2g, p<0.05 vs C57-IF) and AL-free (45.8±5.6g, p<0.05 vs AL-IF) groups. The 24-hour food intakes of C57-IF (8.6±0.9 KCal) and AL-IF (8.8±1.1 KCal) were significantly decreased, compared to C57-free (12.3±1.7 KCal, p<0.05 vs C57-IF) and AL-free (13.3±1.5 KCal, p<0.05 vs AL-IF) groups. The respiratory exchange ratio (RER) of AL-free group (0.62±0.12) was significantly lower than three other groups (p<0.05 vs C57-free, C57-IF and AL-IF, respectively). The E/A ratio (E/A), a diastolic parameter, was decreased in C57-free (1.14±0.21) and AL-free (0.89±0.17) groups, not in C57-IF (2.15±0.31, p<0.05 vs C57-free) and AL-IF (1.97±0.25, p<0.05 vs AL-free) groups. The E/A in AL-free group was also lower than C57-free group (p<0.05). Another diastolic parameter, isovolumic relaxation time (IVRT) was also prolonged in C57-free (27.3±3.3 ms) and AL-free (29.4±3.7 ms) mice, not in C57-IF (13.3±1.8 ms, p<0.05 vs C57-free) and AL-IF (15.2±2.1 ms, p<0.5 vs AL-free) mice. In conclusion, IF decreased food intake and obesity, and improved metabolism and heart function in both C57 and ALDH2*2 mice with HFpEF, and also diminished the differences in RER and E/A between them via lowering the 4HNE adducts.