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

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

PROVIDER: PRJNA532934 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8903370_1.fastq.gz	Fastqsanger.gz
	SRR8903370_2.fastq.gz	Fastqsanger.gz
	SRR8903380_1.fastq.gz	Fastqsanger.gz
	SRR8903380_2.fastq.gz	Fastqsanger.gz
	SRR8903390_1.fastq.gz	Fastqsanger.gz

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

Project description: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.

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

Project description: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.

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Project description:Adipose tissue (AT) oxygen tension (pO2) has been implicated in AT dysfunction and metabolic perturbations in both rodents and humans. Compelling evidence suggests that hypoxia exposure alters metabolism, at least partly through effects on AT. However, it remains to be elucidated whether mild intermittent hypoxia (MIH) exposure impacts the AT proteome. We performed a randomized, single-blind, cross-over study to investigate the effects of seven consecutive days of MIH (FiO2 15%, 3x2h/d) compared to normoxia (FiO2 21%) exposure, on the AT proteome in overweight/obese men. AT insulin sensitivity was determined by a two-step hyperinsulinemic-euglycemic clamp, and abdominal subcutaneous AT biopsies were collected (n=11) under normoxic, fasting conditions following both exposure regimens. AT proteins were isolated and quantified using liquid chromatography-mass spectrometry. After correction for blood contamination, 1022 AT protein IDs were identified, of which 123 were differentially expressed following MIH (p < 0.05). These proteins were involved in redox systems, cell-adhesion, actin cytoskeleton organization, extracellular matrix composition and energy metabolism. We demonstrate for the first time that MIH exposure impacts the AT proteome. Moreover, differential AT TMOD3 expression is related to changes in AT insulin sensitivity, thereby linking MIH-induced effects on the AT proteome to metabolic changes in overweight/obese humans.

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