Diurnal transcriptome landscape of a multi-tissue response to time-restricted feeding in mammals.

Time-restricted feeding (TRF) and Ramadan fasting (RF) have been recently associated with several health outcomes. However, it is not yet clear if they are superior to existing treatments in terms of glucose metabolism, insulin action, and weight loss. This review aims to summarize the current data on the effects of these regimes on body weight, body composition, and glycemia. An electronic search was conducted in PUBMED and SCOPUS databases up to August 2022. Twenty-four records met the inclusion criteria and underwent a risk-of-bias assessment. The main outcomes were: (a) TRF may result in moderate weight loss in individuals with overweight/obesity; when TRF is combined with caloric restriction, weight loss is >5% of the initial body weight, (b) 14 h of fasting may be as effective as 16 h in terms of weight loss, and (c) TRF may lead to improved insulin sensitivity and glycemic responses/variability throughout the day in individuals with overweight/obesity. Concerning RF, only two studies were available and thus, conclusions were not drawn. TRF may be an effective nutritional approach for weight loss, and the amelioration of glycemic control and insulin sensitivity in individuals with overweight/obesity. However, more long-term, well-designed studies are needed.

/pdf/effects-of-time-restricted-feeding-and-ramadan-fasting-on-r9xgg1rp.pdf

Effects of Time-Restricted Feeding and Ramadan Fasting on Body Weight, Body Composition, Glucose Responses, and Insulin Resistance: A Systematic Review of Randomized Controlled Trials

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.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/oby.23499

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

Daily (circadian) rhythms coordinate our physiology and behaviour with regular environmental changes. Molecular clocks in peripheral tissues (e.g. liver, skeletal muscle and adipose) give rise to rhythms in macronutrient metabolism, appetite regulation and the components of energy balance such that our bodies can align the periodic delivery of nutrients with ongoing metabolic requirements. The timing of meals both in absolute terms (i.e. relative to clock time) and in relative terms (i.e. relative to other daily events) is therefore relevant to metabolism and health. Experimental manipulation of feeding–fasting cycles can advance understanding of the effect of absolute and relative timing of meals on metabolism and health. Such studies have extended the overnight fast by regular breakfast omission and revealed that morning fasting can alter the metabolic response to subsequent meals later in the day, whilst also eliciting compensatory behavioural responses (i.e. reduced physical activity). Similarly, restricting energy intake via alternate‐day fasting also has the potential to elicit a compensatory reduction in physical activity, and so can undermine weight‐loss efforts (i.e. to preserve body fat stores). Interrupting the usual overnight fast (and therefore also the usual sleep cycle) by nocturnal feeding has also been examined and further research is needed to understand the importance of this period for either nutritional intervention or nutritional withdrawal. In summary, it is important for dietary guidelines for human health to consider nutrient timing (i.e. when we eat) alongside the conventional focus on nutrient quantity and nutrient quality (i.e. how much we eat and what we eat).

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1113/JP280756

Nutrient timing and metabolic regulation

Exercise exerts many health benefits by directly inducing molecular alterations in physically utilized skeletal muscle. Molecular adaptations of subcutaneous adipose tissue (SCAT) might also contribute to the prevention of metabolic diseases.To characterize the response of human SCAT based on changes in transcripts and mitochondrial respiration to acute and repeated bouts of exercise in comparison to skeletal muscle.Sedentary participants (27 ± 4 yrs) with overweight or obesity underwent 8-week supervised endurance exercise 3×1h/week at 80% VO2peak. Before, 60 min after the first and last exercise bout and 5 days post intervention, biopsies were taken for transcriptomic analyses and high-resolution respirometry (n = 14, 8 female/6 male).In SCAT, we found 37 acutely regulated transcripts (FC > 1.2, FDR < 10%) after the first exercise bout compared to 394, respectively, in skeletal muscle. Regulation of only 5 transcripts overlapped between tissues highlighting their differential response. Upstream and enrichment analyses revealed reduced transcripts of lipid uptake, storage and lipogenesis directly after exercise in SCAT and point to β-adrenergic regulation as potential major driver. The data also suggest an exercise-induced modulation of the circadian clock in SCAT. Neither term was associated with transcriptomic changes in skeletal muscle. No evidence for beigeing/browning was found in SCAT along with unchanged respiration.Adipose tissue responds completely distinct from adaptations of skeletal muscle to exercise. The acute and repeated reduction in transcripts of lipid storage and lipogenesis, interconnected with a modulated circadian rhythm, can counteract metabolic syndrome progression toward diabetes. 

https://www.nature.com/articles/s41366-023-01271-y.pdf

Acute and long-term exercise adaptation of adipose tissue and skeletal muscle in humans: a matched transcriptomics approach after 8-week training-intervention

Adipose tissue (AT) is a key metabolic organ which functions are rhythmically regulated by an endogenous circadian clock. Feeding is a "zeitgeber" aligning the clock in AT with the external time, but mechanisms of this regulation remain largely unclear. We tested the hypothesis that postprandial changes of the hormone insulin directly entrain circadian clocks in AT and investigated a transcriptional-dependent mechanism of this regulation. We analyzed gene expression in subcutaneous AT (SAT) of obese subjects collected before and after the hyperinsulinemic-euglycemic clamp or control saline infusion (SC). The expressions of core clock genes PER2, PER3, and NR1D1 in SAT were differentially changed upon insulin and saline infusion, suggesting insulin-dependent clock regulation. In human stem cell-derived adipocytes, mouse 3T3-L1 cells, and AT explants from mPer2Luc knockin mice, insulin induced a transient increase of the Per2 mRNA and protein expression, leading to the phase shift of circadian oscillations, with similar effects for Per1 Insulin effects were dependent on the region between -64 and -43 in the Per2 promoter but not on CRE and E-box elements. Our results demonstrate that insulin directly regulates circadian clocks in AT and isolated adipocytes, thus representing a primary mechanism of feeding-induced AT clock entrainment.

Insulin Directly Regulates the Circadian Clock in Adipose Tissue.

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Insulin Directly Regulates the Circadian Clock in Adipose Tissue.