Short-Term Time-Restricted Feeding Alters Rhythmicity of Lipid and Amino Acid Metabolites in Overweight Men

Time-restricted feeding improves metabolic health independently of dietary macronutrient composition or energy restriction. To understand the mechanisms underpinning the effects of time-restricted feeding, we investigated the metabolic and transcriptomic profile of skeletal muscle and serum samples from 11 overweight/obese men. In muscle, 4-10% of transcripts and 14% of metabolites were periodic, with the amplitude of the metabolites lower after time-restricted feeding. Core clock genes were unaltered by either intervention, while time-restricted feeding induced rhythmicity of genes related to lipid and amino acid transport. In serum, 49-65% of the metabolites had diurnal rhythms across both conditions, with the majority being lipids. Time-restricted feeding shifted the skeletal muscle metabolite profile from predominantly lipids to amino acids. Our results show time-restricted feeding differentially affects the amplitudes and rhythmicity of serum and skeletal muscle metabolites, and regulates the rhythmicity of genes controlling lipid and amino acid transport, without perturbing the core clock. Overall design: The study employed two experimental dietary conditions and both required participants (11 overweight/obese men) to consume provided meals for five days consisting of ~32% of total energy intake (TEI) from carbohydrate, ~49% TEI from fat, and ~19% of TEI from protein. The timing of dietary intake differed between conditions, where energy was either consumed between a 15 h 'unrestricted' feeding (URF) window of 0700 to 2200 h or an 8 h 'time-restricted' feeding (TRF) window of 1000 to 1800 h. Participants were instructed to consume meals at standardized times throughout both experimental conditions (URF: meals consumed within ±30 min 0700, 1400 and 2100 h; TRF: meals at 1000, 1300 and 1700 h). Food was provided to be consumed on Day 0 (standardized diet) and for the first four days (Day 1-4) of each experimental condition. Instructions were provided on when to consume food (depending on condition). On the fifth day of each condition, participants arrived at ~0630 h and remained in the laboratory until ~0730 h the following day. Samples were obtained from vastus lateralis every 4 hours over 24 hours, to obtain a total of six skeletal muscle biopsies.