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

Abstract

Summary 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 ).

Protocol for setup and circadian analysis of inverted feeding in mice

“… CRITICAL: When performing time-restricted feeding under 12 h light:12 h dark cycles, the 7-day regimen is normally applied and sufficient to entrain the liver clock ( Damiola et al., 2000 ; Stokkan et al., 2001 ; Hara et al., 2001 ). We tested the time of time-restricted feeding for up to 36 days and found consistent phase entrainment in the four tested peripheral tissues, i.e., heart, kidney, liver, and adipose tissue ( Xin et al., 2021 ). Record the food weight daily and body weight weekly.…”

“…To set up inverted feeding paradigm, we used daytime-restricted feeding (DRF) to introduce inverted feeding to mice and nighttime-restricted feeding (NRF) as a control. This procedure is written for a 36-day time-restricted feeding regimen, but it is commonly applied for as short as 7 days in Xin et al., 2021 .…”

“… Note: In our original study, we compared the effects of inverted feeding in both males and females. Please refer to Xin et al., 2021 for details. Briefly, the phenotype is robust in liver and adipose tissue between male and female.…”

“…Briefly, the phenotype is robust in liver and adipose tissue between male and female. Inverted feeding disrupted the rhythms of the majority of selected core clock genes in heart and kidney in males, whereas the rhythms were preserved in females ( Xin et al., 2021 ). Very recently, Manella et al.…”

“…This protocol can be combined with the use of CircaMetDB database for mechanistic studies of inverted feeding. For complete details on the use and execution of this protocol, please refer to Xin et al. (2021) .…”