Effect of Nutrient Delivery Pattern on Biological Rhythms in Human Skeletal Muscle

Human metabolism is regulated on a daily basis via a circadian timing system that coordinates metabolic responses between various tissues. Skeletal muscle is a major site for the oxidation or storage of key metabolites, with recent studies at Bath and Surrey demonstrating biological rhythms in this tissue over a 24-h cycle. It is well established that dysregulated metabolism in skeletal muscle contributes to poor metabolic health and that poor diet is a causal factor in this deterioration. Diet can be characterised by three nutritional considerations: how much is eaten (i.e. quantity/dose), what is eaten (i.e. type) and when it is eaten (i.e. timing). Whilst most dietary approaches and most scientific studies have focused on the first two factors, there is convincing evidence that human health is also dictated by the pattern of nutrient delivery; this includes the frequency and regularity of daily eating occasions, along with their timing both in absolute terms (i.e. time-of-day) and relative to when other inter-related daily events occur - or usually occur (e.g. light exposure, sleep, exercise, etc.). It remains unknown whether the interaction of such factors may affect the biological rhythms previously documented in human skeletal muscle. In particular, from a basic science perspective, the fundamental contrast between frequent versus infrequent feeding warrants investigation. To this end, 16-24 healthy adults will be randomly allocated to receive their individual daily energy requirements delivered via naso-gastric infusion either continuously over 24 hours (n=8-12; CONSTANT) or as two bolus infusions at the start (0800 h) and mid-point (2000 h) of the monitoring period (n=8-12; BOLUS). Serial skeletal muscle (vastus lateralis) biopsies will be sampled every 4 hours over a controlled 24-h sleep-wake cycle.