A multi-tissue multi-omics analysis reveals distinct kineztics in entrainment of diurnal transcriptomes by inverted feeding

Time of eating synchronizes circadian rhythms of metabolism and physiology. Inverted feeding can uncouple peripheral circadian clocks from the central clock located in the suprachiasmatic nucleus. However, system-wide changes of circadian metabolism and physiology entrained to inverted feeding in peripheral tissues remain largely unexplored. Here, we performed a 24-h global profiling of transcripts and metabolites in mouse peripheral tissues to study the transition kinetics during inverted feeding, and revealed distinct kinetics in phase entrainment of diurnal transcriptomes by inverted feeding, which graded from fat tissue (near-completely entrained), liver, kidney, to heart. Phase kinetics of tissue clocks tracked with those of transcriptomes and were gated by light-related cues. Integrated analysis of transcripts and metabolites demonstrated that fatty acid oxidation entrained completely to inverted feeding in heart despite the slow kinetics/resistance of the heart clock to entrainment by feeding. This multi-omics resource defines circadian signatures of inverted feeding in peripheral tissues (www.CircaMetDB.org.cn).

Automated summary

This study investigated the impact of inverted feeding on circadian rhythms of metabolism and physiology in peripheral tissues using global profiling of transcripts and metabolites in mice. The results showed that different tissues exhibit distinct kinetics in phase entrainment of diurnal transcriptomes by inverted feeding, with fat tissue being near-completely entrained. Despite the slow kinetics of the heart clock, fatty acid oxidation in the heart fully entrained to inverted feeding, suggesting complex mechanisms underlying circadian regulation in peripheral tissues.