Time–restricted eating alters the 24‐hour profile of adipose tissue transcriptome in men with obesity

Abstract

Objective: Time-restricted eating (TRE) restores circadian rhythms in mice, but the evidence to support this in humans is limited. The objective of this study was to investigate the effects of TRE on 24-hour profiles of plasma metabolites, glucoregulatory hormones, and the subcutaneous adipose tissue (SAT) transcriptome in humans. Methods: Men (n = 15, age = 63 [4] years, BMI 30.5 [2.4] kg/m 2 ) were recruited. A 35-hour metabolic ward stay was conducted at baseline and after 8 weeks of 10-hour TRE. Assessment included 24-hour profiles of plasma glucose, nonesterified fatty acid (NEFA), triglyceride, glucoregulatory hormones, and the SAT transcriptome. Dim light melatonin onset and cortisol area under the curve were calculated.Results: TRE did not alter dim light melatonin onset but reduced morning cortisol area under the curve. TRE altered 24-hour profiles of insulin, NEFA, triglyceride, and glucose-dependent insulinotropic peptide and increased transcripts of circadian locomotor output cycles protein kaput (CLOCK) and nuclear receptor subfamily 1 group D member 2 (NR1D2) and decreased period circadian regulator 1 (PER1) and nuclear receptor subfamily 1 group D member 1 (NR1D1) at 12:00 AM. The rhythmicity of 450 genes was altered by TRE, which enriched in transcripts for transcription corepressor activity, DNA-binding transcription factor binding, regulation of chromatin organization, and small GTPase binding pathways. Weighted gene coexpression network analysis revealed eigengenes that were correlated with BMI, insulin, and NEFA.Conclusions: TRE restored 24-hour profiles in hormones, metabolites, and genes controlling transcriptional regulation in SAT, which could underpin its metabolic health benefit.

Multiple sclerosis and circadian rhythms: Can diet act as a treatment?

“…136 Similarly, in humans, TRE in form of the religious daytime dry fasting (whereas food is consumed in the night) showed impacts on the circadian system, advancing the circadian phase in blood monocytes by 1.1 h. 137 Another trial on 10-h daytime eating restriction revealed that TRE restores the 24-h profile of adipose tissue transcriptome including rhythms of core clock genes in obese men. 138 Furthermore, TRE trials demonstrated improvements in glucose regulation, insulin sensitivity, blood lipid levels, blood pressure, oxidative stress markers, and quality of life measures, although the effects may differ between early and midday/late eating windows. [139][140][141][142] Some studies showed that TRE affects the gut microbiome, which might contribute to the described metabolic effects of TRE.…”

Circadian‐mediated regulation of cardiometabolic disorders and aging with time‐restricted feeding

“…Recent human studies have confirmed that TRE decreases genes involved in mitochondrial regulation [54] and strengthens circadian clock gene rhythms [55] in subcutaneous adipose tissue. Additionally, transcriptomic analyses have identified transcriptional regulation, small guanosine‐5'‐triphosphatease (GTPase) binding, and proteasome function as key pathways modulated by TRE [54, 55]. Thus, TRE has tremendous therapeutic potential to normalize the metabolic rhythms disrupted in metabolic disorders through many potential mechanisms, broadening its potential impact (Figure 1).…”

“…Additionally, transcriptomics comparing TRF with ALF have identified several pathways modified by TRF that could contribute to its beneficial effects, including clock genes, molecular chaperone T-complex protein ring complex (TRiC)/chaperonin containing T-complex protein 1 (CCT) complex, which is upregulated by TRF, and mitochondrial electron transport chain components, which are downregulated by TRF [3,31]. Recent human studies have confirmed that TRE decreases genes involved in mitochondrial regulation [54] and strengthens circadian clock gene rhythms [55] in subcutaneous adipose tissue. Additionally, transcriptomic analyses have identified transcriptional regulation, small guanosine-5'-triphosphatease (GTPase) binding, and proteasome function as key pathways modulated by TRE [54,55].…”

Kommentar zu „Intervallfasten ab dem Nachmittag verbessert Gewichtsverlust, Blutdruck und Stimmung“

“…Interessant war zudem, dass die Spätesser vermehrt dem "Abendtypus" zugeordnet werden konnten, die nachts länger wachbleiben, morgens später aufstehen und ihre beste kognitive und physische Leistungsfähigkeit am späteren Nachmittag oder Abend aufweisen, und häufiger die Risikovariante CLOCK rs4580 704 trugen [3]. TRE scheint das Potenzial zu haben, ein chrononutritives Instrument zu sein, welches veränderte zirkadiane Rhythmen wiederherzustellen vermag [4]. Es wird vermutlich aber kein für alle Personen gültiges TRE-Schema nach dem Motto "one size fits all" geben.…”

“…TRE scheint das Potenzial zu haben, ein chrononutritives Instrument zu sein, welches veränderte zirkadiane Rhythmen wiederherzustellen vermag 4 . Es wird vermutlich aber kein für alle Personen gültiges TRE-Schema nach dem Motto „one size fits all“ geben.…”