Time Restricted Feeding Ameliorates Cardiac Dysfunction and Impaired Cardiac Metabolism Induced by Simulated Microgravity

Background Microgravity leads to declined cardiac function and remodeling which could cause pathological problems in the postflight period. Time-restricted feeding (TRF), as a form of intermittent fasting, is an emerging approach to improve health, including cardiometabolic metrics, in animals and humans, but whether it could benefit cardiac performance of astronauts in long-term spaceflight, remains unknown. Aims In this study, we investigated the effects of TRF (food access limited to 8 hours every day) on cardiac metabolism and performance under simulated microgravity. Methods and Results Male rats under ad libitum feeding or TRF were subjected to hindlimb unloading (HU) to simulate microgravity. After 6-week intervention, cardiac function was assessed by two-dimensional speckle tracking echocardiography. HU for 6 weeks led to left ventricular dyssynchrony and declined cardiac function. HU also resulted in cardiac atrophy and collagen deposition. All these were ameliorated by TRF except for cardiac atrophy. Futhermore, metabolites in the heart and blood were assessed by liquid chromotography-tandom mass spectrometry. HU suppressed cardiac glucose utilization and glutaminolysis, indicating a suppressed cardiac flexibility, which can also be restored by TRF. Significance Our data demonstrate that TRF improves cardiac glucose and glutamine metabolism, ameliorates cardiac dysfunction and remodeling in the rats exposed to simulated microgravity. Our study shed new lights on the cardiometabolic regulation of TRF and suggest TRF as a potential countermeasure for cardiac protection in long-term spaceflight.