Feeding is one of the most fundamental animal behaviors, and circadian feeding patterns are influential on health and longevity. Many of the dietary interventions (DI) that improve healthspan have been shown to act through circadian control, yet the molecular links connecting circadian rhythms and DI remain unclear. DI such as intermittent fasting may only be effective in times when the animal normally eats. Thus, understanding the natural circadian pattern of feeding, and the mechanisms that regulate the circadian control of hunger, is critical toward designing more effective DI. Using new methods that allow undisturbed real-time measurements of food consumption, locomotor activity, and sleep, we use Drosophila as a model system to identify and investigate genes that underlie the temporal patterning of feeding cycles. These studies take advantage of available fly populations for genome-wide association (GWAS) mapping of quantitative trait loci and use a novel genome- wide epistatic (GWES) approach to search for epistatic interactions between markers. These results will be further analyzed with systems biology network models that we have constructed from publicly available Drosophila data including co-expression, protein-protein interaction, transcription factor- and microRNA-target relationships, and genetic interactions. If successful, our studies will: 1) characterize circadian feeding behavior in Drosophila; 2) pinpoint particular gene variants that modulate them; and 3) determine gene function in underlying patterned feeding. Our proposed studies offer the unique opportunity to define natural feeding patterns and to harness the variation in natural feeding patterns to study circadian feeding regulation at the molecular level. Since many genes involved in circadian and energy-sensing pathways are conserved across organisms, the identification of genetic mechanisms underlying the regulation of innate circadian feeding behavior has the potential to: 1) better our understanding of the basic biology of the relationship between circadian rhythms and DI in promoting healthy aging and 2) inform translational studies of DI across species.
Dietary interventions, including caloric restriction and intermittent fasting, may mitigate the worldwide epidemic of obesity and metabolic syndrome. While there are clear links between dietary interventions and circadian regulation to impact healthy aging, the molecular mechanisms underlying these connections are not fully understood. This project will define genetic pathways that regulate circadian feeding behavior to identify novel genes that might impact circadian entrainment and the response to dietary interventions.
