Intermittent fasting exerts beneficial metabolic effects on blood pressure and cardiac structure by modulating local renin-angiotensin system in the heart of mice fed high-fat or high-fructose diets

Intermittent fasting (IF) sets the preference for fats as fuel and is linked to beneficial metabolic outcomes; however, the effects in the renin-angiotensin system (RAS) in the heart remains to be determined. We hypothesized that IF improves blood pressure and lipid profiles due to a less activated local RAS in the left ventricle of mice, irrespective of the dietary scheme. This study aimed to evaluate the effects of intermittent fasting on cardiovascular parameters and local RAS in the left ventricle (LV) of mice fed either a high-fat (HF) or high-fructose diet (HFru). Metabolic alterations were induced in C57BL/6 mice by providing them free access to a high-fat or a high-fructose (HFru) diet for 8 weeks. Following the 8-week metabolic alteration period, the mice were subjected to the IF protocol in which mice were deprived of food for 24 hours, every other day, for a period of 4 weeks. The IF protocol caused significant reduction in body weight, systolic blood pressure, blood glucose, total cholesterol, and triacylglycerol levels, in addition to augmenting the plasma and urinary uric acid levels, irrespective of the diet. Post IF protocol, beneficial LV remodeling was observed in animals fed either diet and included reduced LV mass, thickness, and cardiomyocyte cross-sectional area. These results comply with the improved RAS modulation, which favored ACE2/MAS receptor axis over the renin/ACE/AT1 axis. In conclusion, the significant decrease in weight brought about as a result of the IF protocol lead to modulation of the local RAS, with the consequential benefit of LV remodeling and reduction in blood pressure, irrespective of the diet.