Abstract
In humans, little is known about the entrainment of peripheral clocks by environmental cues or the circadian transcriptome of peripheral tissues. Meal timing entrains peripheral clocks rhythms of rodents but the effect of this on the human circadian system is unknown. It was hypothesised that meal timing would phase shift peripheral clock rhythms, but not master clock markers. Also hypothesised was that the transcriptome of subcutaneous adipose tissue would be under circadian regulation. Healthy male participants underwent two, separate clinical trials; one gave a food pulse containing 50% of the daily energetic need in one meal during a 4-hour ultradian light/dark cycle; another gave three isocaloric meals at 5-hourly intervals beginning at 0.5 then 5.5 hours after wake under a fixed light/dark cycle. All circadian rhythms were assessed before and after interventions, under constant routine conditions. Master clock marker, melatonin, was not significantly phase shifted by meal timing, as hypothesised. Plasma glucose and leptin rhythms showed large phase shifts in response to meal timing. Plasma triglycerides were minimally phase shifted by food pulse, but not by a change to meal schedule. A 5-hour delay in three isocaloric meals caused approximately a 1-hour delay in clock gene expression in serial adipose biopsies (PER2, PER3) but no shift in expression in whole blood (PER3, REVERB-β). Subcutaneous adipose biopsies taken under controlled conditions revealed that 1% of the transcriptome was circadian, with bimodal distribution of morning and evening peak times. Gene ontology enrichment analysis identified evening peaking probes as primarily involved in lipid metabolism. Morning peaking probes were involved in circadian rhythms and transcriptional regulation. These results demonstrate for the first time that meal timing differentially affects some peripheral, but not central, components of the human circadian system and that key metabolic processes are under circadian variation in the human adipose tissue transcriptome.