Time-Restricted Feeding Maintains Metabolic Homeostasis and Preserves Striated Muscle by Attenuating Obesity and Light-Induced Disruption of Circadian Rhythms in Drosophila melanogaster

摘要

The maintenance of striated muscle is an important determinant of health and longevity. Recently, skeletal muscle has been shown to have secretory functions important for the maintenance of metabolic homeostasis. Constituting 40% of the body's total mass striated tissue is the largest endocrine active organ. In addition, perturbations of the biological clock, the endogenous timekeeping mechanism which regulates important metabolic and physiological functions, is associated with the development of cardiometabolic syndrome, particularly in the context of obesity. The interplay between striated tissues and circadian rhythms in the development of obesity's co-morbidities, such as insulin resistance, chronic inflammation and mitochondrial dysfunction has been grossly overlooked. Here we present a model of obesity and light-induced circadian disruption in striated muscle using Drosophila melanogaster (fruit fly). We establish a model of cardiac and skeletal muscle dysfunction by reproducing hallmark phenotypes in genetic- and diet-induced obese models. We implement a novel dietary intervention to ameliorate obesity-associated dysfunction in striated tissue using time-restricted feeding (TRF) in which food access is limited to certain times of the day without changes to net caloric intake. Previously, our group has shown that TRF attenuates age-associated cardiac dysfunction and improves sleep efficacy in flies. In addition, our data here suggests that TRF can serve as a circadian mediator in order to protect against light-induced skeletal muscle dysfunction. We propose a powerful translational model for obesity-induced metabolic dysregulation, striated tissue dysfunction and provide a novel dietary intervention to combat the current obesity epidemic.