Bath Myorhythms Project

Human Physiology is coordinated by a circadian timing system that synchronises daily cycles of light-dark, wake- sleep, activity-rest and feeding-fasting. The alignment of these behavioural patterns with underlying biological rhythms is closely linked to physiological function, with misalignment linked to chronic metabolic diseases. The vast majority of evidence about rhythms in metabolism comes from studies of rodents, which is remarkable given that rodents differ fundamentally from humans in both behaviour and metabolic regulation. Moreover, almost no research in any species has examined the effects of muscle contractile activity on 24-h rhythms in metabolism. Skeletal muscle is a key site of metabolic regulation and contractile activity is a powerful stimulus to increase metabolism. The researchers have established a novel protocol for serial muscle sampling throughout 24 hours and pilot work completed in preparation for this grant revealed diurnal transcriptomic and lipidomic rhythms in human skeletal muscle. Further development of that protocol has used enteral feeding via a tube which delivers nutrient directly to the stomach to enable constant nutrient delivery (including during sleep), with preliminary data indicating that underlying rhythms in metabolism are responsive to nutrient availability patterns. The researchers will now capitalise on those findings by incorporating multiple isotope tracers within the protocol, thus finally documenting the nature of rhythmic flux in carbohydrate metabolism and protein turnover in human skeletal muscle, and how those rhythms are aligned with timing and patterns of exercise. In summary, participants will stay in the laboratory for 36 hours with 24 hours of constant feeding via nasogastric tube, and muscle and blood sampling. Participants will be allocated to either the early or late exercise group (involving 1 hour of cycling at either 0800 or 2000 h, respectively) or the control group who will rest for the 24 hours.