Background: Time-restricted eating (TRE), limits the eating duration to 6-10 contiguous hours improving cardio-metabolic health (6, 17, 36, 38). However, the effect of TRE on subcutaneous adipose tissue (SAT) clock genes and transcriptomic profile in humans remains unclear.
Aims: To investigate the effects of TRE on 24-hour metabolites, glucoregulatory hormones and SAT transcriptome.
Methods: Men with obesity (N=15, aged 63 ± 4 years, BMI 30.5 ± 2.4 kg/m2) were recruited to a single-arm, open-labelled, within-subjects design (NCT03590158). At baseline and after eight weeks of TRE (eating window of 10 hours per day), a 35-hour metabolic ward stay was conducted. Plasma glucose, insulin, ghrelin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide, non-esterified fatty acid (NEFA), and triglyceride were measured three hourly and the SAT transcriptome was assessed six hourly. Dim light melatonin onset (DLMO) and morning cortisol (sampled hourly from 6am to 12pm) were also examined.
Results: TRE did not alter DLMO (P=0.86), but reduced the cortisol area under the curve (-17.4±9.4ug/L.Hour, P=0.02). TRE also increased the amplitude (0.04±0.01mmol/L, P=0.02; highest at 12am) and advanced the phase (-3±1.2hours, P=0.05) of NEFA and increased the amplitude of triglycerides (0.2±0.1mmol/L, P=0.006; lowest at 12am) and GLP-1 (6.4±2.6pg/mL, P=0.03; highest level at 3pm). Of known clock genes, TRE increased Clock (FDR=0.05) and Nr1d2 (FDR=0.01) and decreased mRNA levels of Per1 (FDR=0.02) and Nr1d1 (FDR=0.02) at 12am only. Overall, 325, 611 and 3423 transcripts were found to be differentially expressed at 6am, 6pm and 12am, respectively, by TRE. Of these, 450 showed variation in the expression pattern over 24-hours following TRE. Pathway analysis showed these genes were involved in transcription corepressor activity and endocytosis.
Conclusion: TRE decreased morning cortisol and advanced the phase of plasma NEFA. The data also suggest there was a phase advance in rhythmic genes in human SAT by TRE.