Time-restricted feeding alters lipid and amino acid metabolite rhythmicity without perturbing clock gene expression

Leonidas S Lundell,Shogo Sato,Lars R Ingerslev,Romain Barrès,Paolo Sassone-Corsi,Juleen R Zierath,Brooke L Devlin,Ali Altıntaş,John A Hawley,Evelyn B Parr

doi:10.1038/s41467-020-18412-w

Abstract

Time-restricted feeding (TRF) improves metabolism independent of dietary macronutrient composition or energy restriction. To elucidate mechanisms underpinning the effects of short-term TRF, we investigated skeletal muscle and serum metabolic and transcriptomic profiles from 11 men with overweight/obesity after TRF (8 h day−1) and extended feeding (EXF, 15 h day−1) in a randomised cross-over design (trial registration: ACTRN12617000165381). Here we show that muscle core clock gene expression was similar after both interventions. TRF increases the amplitude of oscillating muscle transcripts, but not muscle or serum metabolites. In muscle, TRF induces rhythmicity of several amino acid transporter genes and metabolites. In serum, lipids are the largest class of periodic metabolites, while the majority of phase-shifted metabolites are amino acid related. In conclusion, short-term TRF in overweight men affects the rhythmicity of serum and muscle metabolites and regulates the rhythmicity of genes controlling amino acid transport, without perturbing core clock gene expression.

Highlights

Time-restricted feeding (TRF) improves metabolism independent of dietary macronutrient composition or energy restriction
We present the temporal relationship between circulating metabolites and corresponding skeletal muscle metabolite and gene transcript profiles using a short-term (5-day), controlled intervention of isoenergetic TRF (8 h day−1, 1000–1800 h) versus extended feeding (EXF; 15 h day−1, 0700–2200 h) using a crossover design in men with overweight/obesity
T-Distributed Stochastic Neighbor Embedding (t-SNE) clustering of skeletal muscle transcripts after EXF and TRF (Fig. 1d, e) showed clear clustering based on acrophase

Summary

Introduction

Time-restricted feeding (TRF) improves metabolism independent of dietary macronutrient composition or energy restriction. Short-term TRF in overweight men affects the rhythmicity of serum and muscle metabolites and regulates the rhythmicity of genes controlling amino acid transport, without perturbing core clock gene expression. Time-restricted eating decreases body mass by reducing energy intake[11,12], but improves whole-body insulin sensitivity and beta cell responsiveness independent of daily energy intake[8] These results suggest that the interplay of energy intake timing (including time spent fasting), and whole-body circadian rhythmicity have a profound impact on whole-body metabolism and metabolic health. We present the temporal relationship between circulating metabolites and corresponding skeletal muscle metabolite and gene transcript profiles using a short-term (5-day), controlled intervention of isoenergetic TRF (8 h day−1, 1000–1800 h) versus extended feeding (EXF; 15 h day−1, 0700–2200 h) using a crossover design in men with overweight/obesity. Our results provide evidence demonstrating that short-term TRF in men with overweight/obesity affects periodic metabolism, while not influencing the expression of core clock genes

Methods

Results

Conclusion