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Timed feeding drives adipose browning, although the integrative mechanisms for the same remain unclear. Here, we show that twice-a-night (TAN) feeding generates biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed feeding. Insulin and leptin surges lead to marked cellular, functional, and metabolic remodeling of subcutaneous white adipose tissue (sWAT), resulting in increased energy expenditure. Single-cell RNA-sequencing (scRNA-seq) analyses and flow cytometry demonstrate a role for insulin and leptin surges in innate lymphoid type 2 (ILC2) cell recruitment and sWAT browning, since sWAT depot denervation or loss of leptin or insulin receptor signaling or ILC2 recruitment each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day timed co-injections is sufficient to favorably remodel innervated sWAT. Innervation is necessary for sWAT remodeling, since denervation of sWAT, but not brown adipose tissue (BAT), blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, reorganization of nutrient-sensitive pathways remodels sWAT and drives the metabolic benefits of timed feeding.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has surpassed the hepatitis B virus and hepatitis C virus as the leading cause of chronic liver disease in most parts of the Western world. MASLD (formerly known as NAFLD) encompasses both simple steatosis and more aggressive metabolic dysfunction-associated steatohepatitis (MASH), which is accompanied by inflammation, fibrosis, and cirrhosis, and ultimately can lead to hepatocellular carcinoma (HCC). There are currently very few approved therapies for MASH. Weight loss strategies such as caloric restriction can ameliorate the harmful metabolic effect of MASH and inhibit HCC; however, it is difficult to implement and maintain in daily life, especially in individuals diagnosed with HCC. In this study, we tested a time-restricted feeding (TRF) nutritional intervention in mouse models of MASH and HCC. We show that TRF abrogated metabolic dysregulation induced by a Western diet without any calorie restriction or weight loss. TRF improved insulin sensitivity and reduced hyperinsulinemia, liver steatosis, inflammation, and fibrosis. Importantly, TRF inhibited liver tumors in two mouse models of obesity-driven HCC. Our data suggest that TRF is likely to be effective in abrogating MASH and HCC and warrant further studies of time-restricted eating in humans with MASH who are at higher risk of developing HCC.

Time-restricted feeding (TRF) has emerged as a promising dietary approach for improving metabolic parameters associated with obesity. However, it remains largely unclear whether TRF offers benefits for obesity related to exposure to light at night. This study examined whether lean and obese mice under chronic light exposure could benefit from TRF intervention. Six-week-old C57BL/6 male mice were fed either a low-fat diet or a high-fat diet under a 12 h light/12 h dark cycle for 6 weeks. They were then divided into three subgroups: control light, chronic 24 h light, and chronic light with a daily 10 h TRF. Chronic light exposure led to increased weight gain and higher expression of inflammatory and fibrotic markers in the adipose tissue of both lean and obese mice. It also increased hepatic triglyceride content in mice, regardless of their weight status. TRF protected both lean and obese mice from weight gain, normalized inflammatory and fibrotic gene expression, and reduced adipose tissue collagen and liver triglyceride accumulation caused by light exposure alone or in combination with obesity. These results suggest that TRF could have clinical implications for preventing obesity associated with night shift work, regardless of current weight status. [ABSTRACT FROM AUTHOR]

Recent research has highlighted the essential role of the microbiome in maintaining skeletal muscle physiology. The microbiota influences muscle health by regulating lipid metabolism, protein synthesis, and insulin sensitivity. However, metabolic disturbances such as obesity can lead to dysbiosis, impairing muscle function. Time‐restricted feeding (TRF) has been shown to mitigate obesity‐related muscle dysfunction, but its effects on restoring healthy microbiomes remain poorly understood. This study utilizes 16S microbiome analysis and bacterial supplementation to investigate the bacterial communities influenced by TRF that may benefit skeletal muscle physiology. In wild‐type and obese Drosophila models (axenic models devoid of natural microbial communities), the absence of microbiota influence muscle performance and metabolism differently. Specifically, axenic wild‐type Drosophila exhibited reduced muscle performance, higher glucose levels, insulin resistance, ectopic lipid accumulation, and decreased ATP levels. Interestingly, in obese Drosophila (induced by a high‐fat diet or predisposed obesity mutant Sk2), the absence of microbiota improved muscle performance, lowered glucose levels, reduced insulin resistance, and increased ATP levels. TRF was found to modulate microbiota composition, notably increasing Acetobacter pasteurianus (AP) and decreasing Staphylococcus aureus (SA) in both obesity models. Supplementation with AP improved muscle performance and reduced glucose and insulin resistance, while SA supplementation had the opposite effect. This study provides novel insights into the complex interactions between TRF, microbiota, and skeletal muscle physiology in different Drosophila models. [ABSTRACT FROM AUTHOR]

Key points Time‐restricted feeding is known to ameliorate obesity in young mice. However, evaluation of its effect in old age is still lacking. The current work aims to investigate the effects of time‐restricted feeding on treating pre‐existing obesity in old animals. The study utilized middle‐aged and old high fat diet‐induced obese mice and subjected them to 8 h daily time‐restricted feeding. Aged obese mice did not lose fat mass but lost lean mass after 8 weeks of treatment. In addition, time‐restricted feeding reduced adiposity in brown adipose tissue, reversed excessive hepatic lipid accumulation, and improved glucose homeostasis in middle‐aged and old obese mice. Mechanistic studies show that these metabolic benefits were mediated by transcriptional downregulation of essential genes responsible for hepatic adipogenesis and adipose tissue chronic inflammation. These results demonstrate that time‐restricted feeding improves metabolic health and has beneficial effects in combating diet‐induced obesity in aged obese mice. Contrary to in young obese mice, in old obese mice time‐restricted feeding did not significantly reduce body fat but decreased lean mass. Time‐restricted feeding reduced adipose tissue inflammation, reversed fatty liver, and improved glucose homeostasis in aged mice with diet‐induced obesity. Time‐restricted feeding is effective in improving metabolic homeostasis in aged mice, but less effective in terms of reducing obesity. Future studies should investigate the underlying mechanism of how ageing impaired intermittent fasting induced fat loss. [ABSTRACT FROM AUTHOR]

Objective To observe the effects of time-restricted feeding (TRF)on cardiac dysfunction, myocardial remodeling, myocardial mitochondrial structure and function, myocardial oxidative stress response, and myocardial energy metabolism in mice with heart failure with preserved ejection fraction (HFpEF), and to investigate the regulatory role of TRF on the levels of fibroblast growth factor 21 (FGF21)in serum and myocardial tissues, in order to explore the role and mechanism of TRF in ameliorating myocardial injury in HFpEF. Methods Thirty FGF21 knockout (Fgf21-/- )mice were divided into the Fgf21-/- +ALb group and Fgf21-/- +TRF group. Thirty wild-type (WT)mice were divided into the WT+ALb group and WT+TRF group. Mice in all the four groups were fed a 60% high-fat diet, and Nω -nitro-L-arginine methyl ester hydrochloride (L-NAME, 0. 5 g/L)was added to daily drinking water to establish the HFpEF models. Mice in the WT+ TRF group and Fgf21-/- +TRF group underwent TRF, with feeding allowed from 21：00 to 05：00 the next day and fasting during the rest of the time. Mice in the WT+ALb group and Fgf21-/- +ALb group had access to food 24 h a day. After 8 weeks, the myocardial injury-related indicators were observed, including cardiac function (LVEF, E/A, E/E', BNP), myocardial remodeling (HW/TL, mean cross-sectional area of cardiomyocyte, myocardial collagen deposition, and the mRNA levels of fibrosis-related genes Col1a1, Col3a1, Fn1, and CTGF), myocardial mitochondrial structure and function (damaged mitochondria ratio, ATP production, myocardial ATP content, Complex I activity, Complex V activity), myocardial oxidative stress levels (ROS production, SOD activity, MDA content), myocardial energy metabolism (protein expression levels of CD36, CPT1b, the percentage of 13C Ac-CoA, and the mRNA levels of glucose metabolism-related genes Glut1, Glut4, PFK1), as well as FGF21 expression levels in serum and myocardial tissues. Results After 8 weeks of feeding, compared with the WT+ALb group, the E/A, E/E' values and serum BNP level decreased (all P<0. 01), heart weight, HW/TL value and mean cross-sectional area of cardiomyocyte decreased (all P<0. 01), the collagen deposition and the mRNA expression levels of Col1a1, Col3a1, Fn1, CTGF decreased (all P<0. 01), the proportion of damaged mitochondria decreased, mitochondrial ATP production and activities of mitochondrial complex Ⅰ and Ⅴ increased (all P< 0. 01), myocardial ROS production and MDA content decreased, SOD activity increased (all P<0. 01), the protein expression levels of CD36 and CPT1b increased, the percentage of 13C Ac-CoA increased (all P<0. 01), the mRNA expression levels of Glut1, Glut4 and PFK1 decreased (all P<0. 01), and the serum FGF21 level and the myocardial FGF21 protein and mRNA expression levels increased in the WT+TRF group (all P<0. 01). Compared with the WT+TRF group, the E/A, E/E' values and serum BNP levels increased (all P<0. 01), heart weight, HW/TL value and mean cross-sectional area of cardiomyocyte increased (all P<0. 01), the collagen deposition and mRNA expression levels of Col1a1, Col3a1, Fn1, CTGF increased (all P<0. 01), the proportion of damaged mitochondria increased, mitochondrial ATP production and the activities of mitochondrial complex Ⅰ and Ⅴ decreased (all P<0. 01), myocardial ROS production and MDA content increased, SOD activity decreased (all P<0. 01), the protein expression levels of CD36 and CPT1b decreased, the percentage of 13C Ac-CoA decreased (all P<0. 01), and the mRNA expression levels of Glut1, Glut4 and PFK1 increased in Fgf21-/- +TRF group (all P<0. 01). Conclusions TRF has beneficial effects on cardiac function, myocardial remodeling, myocardial mitochondrial structure and function, myocardial oxidative stress response, and myocardial energy metabolism in mice with HFpEF. Additionally, it promotes the expression of FGF21. By elevating the expression level of FGF21, TRF can enhance myocardial fatty acid metabolism, improve myocardial mitochondrial structural and function, and inhibit oxidative stress levels, thereby ameliorating cardiac dysfunction and myocardial remodeling in HFpEF mice, and ultimate‐ ly mitigating myocardial injury. [ABSTRACT FROM AUTHOR]

Background: This systematic review and meta-analysis examined the synergistic impact of time-restricted feeding (TRF) combined with resistance training (RT) (TRF + RT) on body composition and metabolic health in adults, contrasting it with habitual eating patterns (CON) and RT (CON + RT). Methods: Adhering to PRISMA guidelines, five databases were searched up to 28 April 2024. Randomized controlled trials or crossover trials assessing the effects of TRF + RT for at least 4 weeks in adults were selected. Data were pooled as standardized mean differences (SMDs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs). The risk of bias was evaluated using the revised Cochrane risk-of-bias tool. Results: Seven studies with 164 participants were included in the final analysis. TRF + RT significantly reduced body mass (WMD −2.90, 95% CI: −5.30 to −0.51), fat mass (WMD −1.52, 95% CI: −2.30 to −0.75), insulin (SMD −0.72, 95% CI: −1.24 to −0.21), total cholesterol (WMD −9.44, 95% CI: −13.62 to −5.27), low-density lipoprotein cholesterol (LDL-C) (WMD −9.94, 95% CI: −13.47 to −6.41), and energy intake (WMD −174.88, 95% CI: −283.79 to −65.97) compared to CON + RT. No significant changes were observed in muscle mass, strength, or other metabolic markers. Conclusions: TRF + RT, in contrast to CON + RT, significantly improved body composition, insulin, and cholesterol levels without affecting muscle mass or strength. [ABSTRACT FROM AUTHOR]

To assess the effects of a time-restricted feeding (TRF) regimen on meat quality of pigs exposed to high ambient temperature, a two-month feeding and heat treatment (HT) trial was conducted using a 2 × 2 factorial design. A total of 24 growing pigs (11.0 ± 1.9 kg) were randomly divided into four groups: thermal neutral group (NT, 24 ± 3 °C), HT group (exposed to a high temperature at 35 ± 2 °C from 11:00 to 15:00), TRF group and HT + TRF group (HT and TRF co-treatment group, n = 6 for each group). Pigs in TRF groups got access to feed within 5 h from 9:00 to14:00, while the others were fed at 6:00, 11:30, and 16:00. All pigs received the same diet during the trail. The results showed that HT increased the drip loss, shear force, lightness, and malondialdehyde production in Longissimus thoracis et lumborum (LTL) muscle. TRF reversely reduced the shear force and drip loss, accompanied by decreased intramuscular fat and increased moisture content. Enhanced fiber transformation from type 1 to type 2b and down-regulated expression of muscle growth-related genes were observed by HT, while TRF suppressed the fiber transformation and expression of muscle atrophy-related genes. Furthermore, TRF restored the diminished protein expressions of Nrf2 and HO-1 in LTL muscle by chronic HT. Accumulation of HSP70 in muscle of HT group was reduced by treatment of TRF. HT declined the expression of vital genes involved in fatty acids poly-desaturation and the proportion of (polyunsaturated fatty acids) PUFAs, mainly omega-6 in LTL muscle, while TRF group promoted the expression of poly-desaturation pathway and displayed the highest proportion of PUFAs. These results demonstrated that TRF relieved the chronic high temperature affected meat quality by the restored expression of Nrf2/HO-1 anti-oxidative cascade, modified muscle fiber composition, and enriched PUFAs in LTL muscle. [ABSTRACT FROM AUTHOR]

Abstract To assess the effects of a time-restricted feeding (TRF) regimen on meat quality of pigs exposed to high ambient temperature, a two-month feeding and heat treatment (HT) trial was conducted using a 2 × 2 factorial design. A total of 24 growing pigs (11.0 ± 1.9 kg) were randomly divided into four groups: thermal neutral group (NT, 24 ± 3 °C), HT group (exposed to a high temperature at 35 ± 2 °C from 11:00 to 15:00), TRF group and HT + TRF group (HT and TRF co-treatment group, n = 6 for each group). Pigs in TRF groups got access to feed within 5 h from 9:00 to14:00, while the others were fed at 6:00, 11:30, and 16:00. All pigs received the same diet during the trail. The results showed that HT increased the drip loss, shear force, lightness, and malondialdehyde production in Longissimus thoracis et lumborum (LTL) muscle. TRF reversely reduced the shear force and drip loss, accompanied by decreased intramuscular fat and increased moisture content. Enhanced fiber transformation from type 1 to type 2b and down-regulated expression of muscle growth-related genes were observed by HT, while TRF suppressed the fiber transformation and expression of muscle atrophy-related genes. Furthermore, TRF restored the diminished protein expressions of Nrf2 and HO-1 in LTL muscle by chronic HT. Accumulation of HSP70 in muscle of HT group was reduced by treatment of TRF. HT declined the expression of vital genes involved in fatty acids poly-desaturation and the proportion of (polyunsaturated fatty acids) PUFAs, mainly omega-6 in LTL muscle, while TRF group promoted the expression of poly-desaturation pathway and displayed the highest proportion of PUFAs. These results demonstrated that TRF relieved the chronic high temperature affected meat quality by the restored expression of Nrf2/HO-1 anti-oxidative cascade, modified muscle fiber composition, and enriched PUFAs in LTL muscle.

Circadian disruptions impact nearly all people with Alzheimer's disease (AD), emphasizing both their potential role in pathology and the critical need to investigate the therapeutic potential of circadian-modulating interventions. Here, we show that time-restricted feeding (TRF) without caloric restriction improved key disease components including behavioral timing, disease pathology, hippocampal transcription, and memory in two transgenic (TG) mouse models of AD. We found that TRF had the remarkable capability of simultaneously reducing amyloid deposition, increasing Aβ42 clearance, improving sleep and memory, and normalizing daily transcription patterns of multiple genes, including those associated with AD and neuroinflammation. Thus, our study unveils for the first time the pleiotropic nature of timed feeding on AD, which has far-reaching effects beyond metabolism, ameliorating neurodegeneration and the misalignment of circadian rhythmicity. Since TRF can substantially modify disease trajectory, this intervention has immediate translational potential, addressing the urgent demand for accessible approaches to reduce or halt AD progression.

Abstract Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, and it is characterized by a series of fatty liver diseases that can lead to severe liver disease. Although no therapeutic drug has been approved as an effective therapy for NAFLD to date, dietary changes and physical activity are thought to be the cornerstone of NAFLD management. For this reason, some articles are available to analyze the studies done so far using various modifications of intermittent fasting (IF) among animals and patients with NAFLD. Data from preclinical and clinical trials suggested that IF positively impacts inflammatory and metabolic markers in both animals and humans. Inflammation and oxidative stress are the major risk factors involved in the pathogenesis of NAFLD. IF has been shown to have positive benefits in alleviating metabolic disorders, promoting the browning of white tissue, resetting circadian rhythm, and activating autophagy of cells. This review is intended to provide a detailed synopsis of the protocols, potential mechanisms of action, and supporting evidence for IF in NAFLD. We will highlight what is currently known about IF approaches in NAFLD treatments in clinical populations with mechanism insight from animal studies, and the safety concerns in certain patient groups. Graphical Abstract The protocols of intermittent fasting (IF) are various. Data from trials suggested that IF positively impacts both humans and animals. IF has been shown to have potential treatments for nonalcoholic fatty liver disease.

It has been widely reported that obesity adversely impacts reproductive performance of females. However, the effects of maternal obesity on fetal germ cells remain poorly understood. In the present study, by employing a high‐fat diet (HFD)‐based mouse model, it is discovered that maternal obesity disrupts the chromosomal synapsis and homologous recombination during fetal oogenesis. Moreover, transcriptomic profiling reveales the potential molecular network controlling this process. Of note, the global hypermethylation of genomic DNA in fetal oocytes from obese mouse is detected. Importantly, time‐restricted feeding (TRF) of obese mice not only ameliorate the meiotic defects, but also partly restore the epigenetic remodeling in fetal oocytes. In sum, the evidence are provided showing the deficit fetal oogenesis in obese mother, implicating a mechanism underlying the intergenerational effects of environmental insults. TRF may represent a potentially effective approach for mitigating fertility issues in obese patients. [ABSTRACT FROM AUTHOR]

Introduction: The relationships between the feeding rhythm, sleep and cognition in Alzheimer's disease (AD) are incompletely understood, but meal time could provide an easy-to-implement method of curtailing disease-associated disruptions in sleep and cognition. Furthermore, known sex differences in AD incidence could relate to sex differences in circadian rhythm/sleep/cognition interactions. Methods: The 5xFAD transgenic mouse model of AD and non-transgenic wild-type controls were studied. Both female and male mice were used. Food access was restricted each day to either the 12-h light phase (light-fed groups) or the 12-h dark phase (dark-fed groups). Sleep (electroencephalographic/ electromyographic) recording and cognitive behavior measures were collected. Results: The 5xFAD genotype reduces NREM and REM as well as the number of sleep spindles. In wild-type mice, light-fed groups had disrupted vigilance state amounts, characteristics, and rhythms relative to dark-fed groups. These feeding time differences were reduced in 5xFAD mice. Sex modulates these effects. 5xFAD mice display poorer spatial memory that, in female mice, is curtailed by dark phase feeding. Similarly, female 5xFAD mice have decreased anxiety-associated behavior. These emotional and cognitive measures are correlated with REM amount. Discussion: Our study demonstrates that the timing of feeding can alter many aspects of wake, NREM and REM. Unexpectedly, 5xFAD mice are less sensitive to these feeding time effects. 5xFAD mice demonstrate deficits in cognition which are correlated with REM, suggesting that this circadian-timed aspect of sleep may link feeding time and cognition. Sex plays an important role in regulating the impact of feeding time on sleep and cognition in both wild-type and 5xFAD mice, with females showing a greater cognitive response to feeding time than males. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, and it is characterized by a series of fatty liver diseases that can lead to severe liver disease. Although no therapeutic drug has been approved as an effective therapy for NAFLD to date, dietary changes and physical activity are thought to be the cornerstone of NAFLD management. For this reason, some articles are available to analyze the studies done so far using various modifications of intermittent fasting (IF) among animals and patients with NAFLD. Data from preclinical and clinical trials suggested that IF positively impacts inflammatory and metabolic markers in both animals and humans. Inflammation and oxidative stress are the major risk factors involved in the pathogenesis of NAFLD. IF has been shown to have positive benefits in alleviating metabolic disorders, promoting the browning of white tissue, resetting circadian rhythm, and activating autophagy of cells. This review is intended to provide a detailed synopsis of the protocols, potential mechanisms of action, and supporting evidence for IF in NAFLD. We will highlight what is currently known about IF approaches in NAFLD treatments in clinical populations with mechanism insight from animal studies, and the safety concerns in certain patient groups. The protocols of intermittent fasting (IF) are various. Data from trials suggested that IF positively impacts both humans and animals. IF has been shown to have potential treatments for nonalcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]

The time of day that we eat is increasingly recognized as contributing as importantly to overall health as the amount or quality of the food we eat. The endogenous circadian clock has evolved to promote intake at optimal times when an organism is intended to be awake and active, but electric lights and abundant food allow eating around the clock with deleterious health outcomes. In this review, we highlight literature pertaining to the effects of food timing on health, beginning with animal models and then translation into human experiments. We emphasize the pitfalls and opportunities that technological advances bring in bettering understanding of eating behaviors and their association with health and disease. There is great promise for restricting the timing of food intake both in clinical interventions and in public health campaigns for improving health via nonpharmacological therapies. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion injury (IRI) in the kidneys is a major cause of acute kidney injury (AKI). Time-restricted feeding (TRF), known for its metabolic health benefits and alleviation of various chronic diseases without calorie restriction, was investigated for its potential protective effects against IRI-induced AKI. Male C57BL/6 mice underwent unilateral IRI, with their kidneys collected after two days. For two weeks before IRI induction, the TRF group had unlimited access to standard chow but within an 8-hour feeding window during the dark cycle. The study groups were Control, TRF, IRI, and TRF + IRI. In the TRF + IRI group, tubular damage scores significantly decreased compared to the IRI group. Furthermore, the TRF + IRI mice had lower levels of phosphorylated NF-κB and fewer F4/80-positive macrophages than the IRI group. Oxidative stress markers for lipids and proteins were also notably lower in the TRF + IRI group. Additionally, TUNEL-positive tubular cells and cleaved caspase-3 expression were reduced in the TRF + IRI group. Without calorie restriction, TRF mitigated renal damage by reducing inflammation, oxidative stress, and tubular apoptosis in renal IRI. This suggests that TRF could be a promising dietary strategy to prevent IRI-induced AKI. [ABSTRACT FROM AUTHOR]

Circadian disruption is associated with an increased risk of cardiometabolic disorders and cardiac diseases. Time‐restricted feeding/eating (TRF/TRE), restricting food intake within a consistent window of the day, has shown improvements in heart function from flies and mice to humans. However, whether and how TRF still conveys cardiac benefits in the context of circadian disruption remains unclear. Here, we demonstrate that TRF sustains cardiac performance, myofibrillar organization, and regulates cardiac lipid accumulation in Drosophila when the circadian rhythm is disrupted by constant light. TRF induces oscillations in the expression of genes associated with triglyceride metabolism. In particular, TRF induces diurnal expression of diacylglycerol O‐acyltransferase 2 (Dgat2), peaking during the feeding period. Heart‐specific manipulation of Dgat2 modulates cardiac function and lipid droplet accumulation. Strikingly, heart‐specific overexpression of human Dgat2 at ZT 0–10 significantly improves cardiac performance in flies exposed to constant light. We have demonstrated that TRF effectively attenuates cardiac decline induced by circadian disruption. Moreover, our data suggests that diurnal expression of Dgat2 induced by TRF is beneficial for heart health under circadian disruption. Overall, our findings have underscored the relevance of TRF in preserving heart health under circadian disruptions and provided potential targets, such as Dgat2, and strategies for therapeutic interventions in mitigating cardiac aging, metabolic disorders, and cardiac diseases in humans. [ABSTRACT FROM AUTHOR]

Introduction: The aims of the present study were to evaluate postural balance performance of the subjects on the time-restricted feeding (TRF) and reveal the effect of TRF on the vestibular system by comparing the results to those of traditional daily dietary (DD) condition. Methods: Sixteen adults (3 males, 13 females; mean age: 25.4 ± 4 years) who had experienced at least 1 month of TRF were included in the study. The Sensory Organization Test (SOT) and Head-Shake SOT (HS-SOT) – which evaluate proprioceptive, visual, and vestibular systems – were performed on TRF and DD conditions via the Computerized Dynamic Posturography system. Results: Significant differences were obtained between TRF and DD situations in SOT-5 (p = 0.008), SOT-6 (p = 0.01), and HS-SOT5 (p = 0.007) conditions in which the vestibular system dominated. Conclusion: We revealed that TRF has an effect on postural balance in the absence of proprioceptive and visual systems. This feeding model is a negative stressor that has a substantial effect on the vestibular system, but this impact is minimal once the proprioceptive and visual systems are intact. To the best of our knowledge, it is the first study to evaluate postural balance utilizing vestibular parameters in TRF. [ABSTRACT FROM AUTHOR]

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Liver-expressed antimicrobial peptide-2 (LEAP-2) has mutual antagonism with ghrelin, which evokes food intake under a freely fed state. Nevertheless, the impact of LEAP-2 on ghrelin under time-restricted feeding (TRF), which has benefits in the context of metabolic disease, is still unknown. This study aims to explore the impact of central administration of LEAP-2 on the ingestion behavior of rats, which was evaluated using their cumulative food intake in the TRF state. Before intracerebroventricular (ICV) administration of O-n-octanoylated ghrelin (0.1 nmol/rat), as a food-stimulatory model, the rats received various doses of LEAP-2 (0.3, 1, 3 nmol/rat, ICV). Cumulative food intake was recorded at 1, 2, 4, 8, 12, and 24 h after ICV injection under 12 h freely fed and TRF states in a light phase. In 12 h freely fed and TRF states, central administration of ghrelin alone induced feeding behavior. Pre-treatment with LEAP-2 (1 and 3 nmol/rat, ICV) suppressed ghrelin-induced food intake in a dose-dependent manner in a 12 h freely fed state instead of a TRF state, which may have disturbed the balance of ghrelin and LEAP-2. This study provides neuroendocrine-based evidence that may explain why TRF sometimes fails in fighting obesity/metabolic dysfunction-associated steatotic liver disease in clinics. [ABSTRACT FROM AUTHOR]

Circadian biology's impact on human physical health and its role in disease development and progression is widely recognized. The forefront of circadian rhythm research now focuses on translational applications to clinical medicine, aiming to enhance disease diagnosis, prognosis, and treatment responses. However, the field of circadian medicine has predominantly concentrated on human healthcare, neglecting its potential for transformative applications in veterinary medicine, thereby overlooking opportunities to improve non-human animal health and welfare. This review consists of three main sections. The first section focuses on the translational potential of circadian medicine into current industry practices of agricultural animals, with a particular emphasis on horses, broiler chickens, and laying hens. The second section delves into the potential applications of circadian medicine in small animal veterinary care, primarily focusing on our companion animals, namely dogs and cats. The final section explores emerging frontiers in circadian medicine, encompassing aquaculture, veterinary hospital care, and non-human animal welfare and concludes with the integration of One Health principles. In summary, circadian medicine represents a highly promising field of medicine that holds the potential to significantly enhance the clinical care and overall health of all animals, extending its impact beyond human healthcare. [ABSTRACT FROM AUTHOR]

Chrono-nutrition (meal timing) aligns food consumption with one's circadian rhythm. The first meal (e.g., breakfast) likely promotes synchronization of peripheral circadian clocks, thereby supporting metabolic health. Time-restricted feeding (TRF) has been shown to reduce body weight (BW) and/or improve cardiovascular biomarkers. In this explorative literature assessment, 13 TRF randomized controlled trials (RCTs) were selected from PubMed and Scopus to evaluate the effects of early (eTRF: first meal before 10:30 a.m.) and late TRF (lTRF: first meal after 11:30 a.m.) on parameters of metabolic health. Although distinct variations in study design were evident between reports, TRF consistently decreased energy intake (EI) and BW, and improved insulin resistance as well as systolic blood pressure. eTRF seemed to have a greater beneficial effect than lTRF on insulin resistance (HOMA-IR). Importantly, most studies did not appear to consider chronotype in their evaluation, which may have underestimated TRF effects. TRF intervention may be a promising approach for risk reduction of human metabolic diseases. To conclusively determine benefits of TRF and identify clear differences between eTRF and lTRF, future studies should be longer-term (≥8 weeks) with well-defined (differences in) feeding windows, include participants chronotypically matching the intervention, and compare outcomes to those of control groups without any dietary limitations. [ABSTRACT FROM AUTHOR]

Circadian rhythmicity optimizes the health and physiology by coordinating temporally the cellular functions, tissue functions, and behavior. These endogenously generated rhythms gets dampen with age and therefore compromise the temporal coordination. The pattern of fasting and feeding sets an external cue that profoundly influences the robustness of daily circadian rhythms. Irregular eating patterns can change the temporal coordination of physiology and metabolism leading to chronic diseases. Robust sustaining of fasting and feeding cycle, without altering nutrition quality, can reverse or prevent the chronic diseases as already depicted in an animal model. However, in humans, studies have shown that erratic pattern of eating can elevate the risk of diseases, whereas sustained fasting and feeding cycle, or prolonged overnight fasting, is correlated with protection from different cancers. Therefore, by just optimizing the external cues timing well defined eating patterns, can thus sustain a robust circadian clock, which may result in preventing many diseases and can improve the prognosis. Time-restricted feeding (TRF) is a form of intermittent fasting, comprising a longer daily fasting period. Preliminary studies report that TRF improves cardiometabolic diseases, diabetes and cancer in rodents and humans. [ABSTRACT FROM AUTHOR]

Skeletal muscle plays a critical role in regulating systemic metabolic homeostasis. It has been demonstrated that time-restricted feeding (TRF) during the rest phase can desynchronize the suprachiasmatic nucleus (SCN) and peripheral clocks, thereby increasing the risk of metabolic diseases. However, the impact of dietary timing on the muscle clock and health remains poorly understood. Here, through the analysis of cycling genes and differentially expressed genes in the skeletal muscle transcriptome, we identified disruptions in muscle diurnal rhythms by 2 weeks of light-phase TRF. Furthermore, compared with ad libitum (AL) feeding mice, 2 weeks of light-phase TRF was found to induce insulin resistance, muscle fiber type remodeling, and changes in the expression of muscle growth-related genes, while both light-phase and dark-phase TRF having a limited impact on bone quality relative to AL mice. In summary, our research reveals that the disruption of the skeletal muscle clock may contribute to the abnormal metabolic phenotype resulting from feeding restricted to the inactive period. Additionally, our study provides a comprehensive omics atlas of the diurnal rhythms in skeletal muscle regulated by dietary timing.

Dietary modifications such as caloric restriction (CR) and intermittent fasting (IF) have gained popularity due to their proven health benefits in aged populations. In time restricted feeding (TRF), a form of intermittent fasting, the amount of time for food intake is regulated without restricting the caloric intake. TRF is beneficial for the central nervous system to support brain health in the context of aging. Therefore, we here ask whether TRF also exerts beneficial effects in the aged retina. We compared aged mice (24 months) on a TRF paradigm (access to food for six hours per day) for either 6 or 12 months against young control mice (8 months) and aged control mice on an ad libitum diet. We examined changes in the retina at the functional (electroretinography), structural (histology and fluorescein angiograms) and molecular (gene expression) level. TRF treatment showed amelioration of age-related reductions in both scotopic and photopic b-wave amplitudes suggesting benefits for retinal interneuron signaling. TRF did not affect age-related signs of retinal inflammation or microglial activation at either the molecular or histological level. Our data indicate that TRF helps preserve some aspects of retinal function that are decreased with aging, adding to our understanding of the health benefits that altered feeding patterns may confer.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a global health concern, lacking specific therapeutic strategies. Time-restricted feeding (TRF) regimen demonstrated beneficial effects in NAFLD; however, the underlying mechanisms remain unclear. In this study, we established a NAFLD mouse model through a high-fat diet (HFD) and implemented the 16:8 TRF regimen for a duration of 6 weeks. We demonstrated that TRF remarkably alleviated hepatic steatosis in HFD mice. Of note, aldehyde oxidase 1 (AOX1), a key enzyme in hepatic nicotinamide (NAM) catabolism, exhibited apparent upregulation in response to HFD, leading to abnormal accumulation of N-Methyl-6-pyridone-3-carboxamide (N-Me-6-PY, also known as 2PY) and N-Methyl-4-pyridone-5-carboxamide (N-Me-4-PY, also known as 4PY), whereas it was almost restored by TRF. Both N-Me-6-PY and N-Me-4-PY promoted de novo lipogenesis and fatty acid uptake capacities in hepatocyte, and aggravated hepatic steatosis in mice either fed chow diet or HFD. In contrast, pharmacological inhibition of AOX1 was sufficient to ameliorate the hepatic steatosis and lipid metabolic dysregulation induced by HFD. Moreover, transplantation of fecal microbiota efficiently mimicked the modulatory effect of TRF on NAM metabolism, thus mitigating hepatic steatosis and lipid metabolic disturbance, suggesting a gut microbiota-dependent manner. In conclusion, our study reveals the intricate relationship between host NAM metabolic modification and gut microbiota remodeling during the amelioration of NAFLD by TRF, providing promising insights into the prevention and treatment of NAFLD.

The effects of intermittent fasting (IF) on health promotion in the healthy population remain controversial. Therefore, our study aimed to analyse the efficacy and feasibility of different IF protocols and evaluated the effects within a cohort with a controlled-run in phase on the body mass index (BMI) as the primary outcome, the body composition, and metabolic and haematological markers in healthy participants. A total of 25 individuals were randomised into three fasting groups: 16/8 fasting (n = 11), 20/4 fasting (n = 6), and alternate-day fasting (ADF, n = 8). Assessments were conducted at baseline (visit 1), after a four-week controlled-run in phase (visit 2), and after eight weeks of fasting (visit 3). Both the BMI (p = 0.01) and bodyweight (p = 0.01) were significantly reduced in the ADF group, which was not seen in the 16/8 and 20/4 groups (p > 0.05). Adherence was different but not statistically among the groups (16/8: 84.5 ± 23.0%; 20/4: 92.7 ± 9.5%; and ADF: 78.1 ± 33.5%, p = 0.57). Based on our obtained results, the data suggest that some fasting interventions might be promising for metabolic health. However, adherence to the specific fasting protocols remains challenging even for the healthy population. [ABSTRACT FROM AUTHOR]

Background: The concept of time-restricted eating (TRE) or time-restricted feeding (TRF) promotes daily periods of feeding and fasting to determine whole-body physiology. Chronic misalignment of circadian rhythms or chrono-disruption is related to an increased risk of diverse metabolic disorders. The progression of non-communicable diseases seems to be affected by the timing of meals. As a result, intermittent fasting is a promising approach for their management. The aim of the present literature review is to examine and scrutinize the TRE protocols in the fields of prevention and management of metabolic disorders. Methods: This is a thorough literature review of the reported associations among circadian rhythm, metabolic disorders, diabetes mellitus, obesity, TRE, TRF, dietary habits, circadian disruption, cardiovascular diseases, atherosclerosis, and non-alcoholic fatty liver to find the already existing clinical studies from the last decade (2014–2024) in the most precise scientific online databases, using relevant specific keywords. Several inclusion and exclusion criteria were applied to scrutinize only longitudinal, cross-sectional, descriptive, and prospective clinical human studies. Results: The currently available clinical findings remain scarce and suggest that chrononutrition behaviors such as TRE or TRF may promote several metabolic benefits, mainly in body weight control and fat loss. Improvements in glucose levels and lipid profiles are currently quite controversial since some clinical studies show little or no effect. As far as liver diseases are concerned, the efficacy of intermittent fasting seems to be stronger in the management of non-alcoholic fatty liver disease due to body weight decline and fat loss. Conclusions: Even if there has been a gradual increase in clinical studies in the last few years, providing promising perspectives, currently, there is no conclusive evidence for the role of chrononutrition in metabolic disorders. Future studies should be well-designed with longer duration and larger sample sizes. Moreover, it is important to examine the best timing of the eating window and its feasibility. [ABSTRACT FROM AUTHOR]

Abstract It has been widely reported that obesity adversely impacts reproductive performance of females. However, the effects of maternal obesity on fetal germ cells remain poorly understood. In the present study, by employing a high‐fat diet (HFD)‐based mouse model, it is discovered that maternal obesity disrupts the chromosomal synapsis and homologous recombination during fetal oogenesis. Moreover, transcriptomic profiling reveales the potential molecular network controlling this process. Of note, the global hypermethylation of genomic DNA in fetal oocytes from obese mouse is detected. Importantly, time‐restricted feeding (TRF) of obese mice not only ameliorate the meiotic defects, but also partly restore the epigenetic remodeling in fetal oocytes. In sum, the evidence are provided showing the deficit fetal oogenesis in obese mother, implicating a mechanism underlying the intergenerational effects of environmental insults. TRF may represent a potentially effective approach for mitigating fertility issues in obese patients.

IntroductionThe relationships between the feeding rhythm, sleep and cognition in Alzheimer’s disease (AD) are incompletely understood, but meal time could provide an easy-to-implement method of curtailing disease-associated disruptions in sleep and cognition. Furthermore, known sex differences in AD incidence could relate to sex differences in circadian rhythm/sleep/cognition interactions.MethodsThe 5xFAD transgenic mouse model of AD and non-transgenic wild-type controls were studied. Both female and male mice were used. Food access was restricted each day to either the 12-h light phase (light-fed groups) or the 12-h dark phase (dark-fed groups). Sleep (electroencephalographic/electromyographic) recording and cognitive behavior measures were collected.ResultsThe 5xFAD genotype reduces NREM and REM as well as the number of sleep spindles. In wild-type mice, light-fed groups had disrupted vigilance state amounts, characteristics, and rhythms relative to dark-fed groups. These feeding time differences were reduced in 5xFAD mice. Sex modulates these effects. 5xFAD mice display poorer spatial memory that, in female mice, is curtailed by dark phase feeding. Similarly, female 5xFAD mice have decreased anxiety-associated behavior. These emotional and cognitive measures are correlated with REM amount.DiscussionOur study demonstrates that the timing of feeding can alter many aspects of wake, NREM and REM. Unexpectedly, 5xFAD mice are less sensitive to these feeding time effects. 5xFAD mice demonstrate deficits in cognition which are correlated with REM, suggesting that this circadian-timed aspect of sleep may link feeding time and cognition. Sex plays an important role in regulating the impact of feeding time on sleep and cognition in both wild-type and 5xFAD mice, with females showing a greater cognitive response to feeding time than males.

IntroductionTime-restricted eating (TRE), a dietary pattern reducing the duration of daily food consumption, has recently gained popularity. Existing studies show the potential benefits of TRE for cardiometabolic health. Uncertainty remains about whether these benefits are solely from altered meal timing or influences on other health behaviors, including sleep. Despite growing scientific interest in the effects of TRE on sleep parameters, the topic has not been systematically explored.MethodsThis review examined the effects of TRE interventions (daily fasting duration ≥14 h) lasting at least 8 weeks on objective and subjective sleep parameters. Six randomized control trials were identified through Pubmed, Embase, Google Scholar, and Scopus through September 2023.ResultsOf the included studies, three employed objective sleep measures using wearables and five studies assessed sleep subjectively through self-report questionnaires. Only one study reported significant improvements in subjective sleep quality following a TRE intervention. Additionally, one study found significant decreases in sleep duration, two studies found significant decreases in sleep efficiency, and one found significant increases in sleep onset latency.DiscussionCurrent evidence indicates that short to mid-term TRE does not typically worsen sleep parameters. However, some populations may experience reduced sleep disturbances, while others may experience reductions in sleep efficiency. Longer duration studies with objective sleep assessments are needed to better understand the effects of TRE on sleep parameters.

Background: This systematic review and meta-analysis examined the synergistic impact of time-restricted feeding (TRF) combined with resistance training (RT) (TRF + RT) on body composition and metabolic health in adults, contrasting it with habitual eating patterns (CON) and RT (CON + RT). Methods: Adhering to PRISMA guidelines, five databases were searched up to 28 April 2024. Randomized controlled trials or crossover trials assessing the effects of TRF + RT for at least 4 weeks in adults were selected. Data were pooled as standardized mean differences (SMDs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs). The risk of bias was evaluated using the revised Cochrane risk-of-bias tool. Results: Seven studies with 164 participants were included in the final analysis. TRF + RT significantly reduced body mass (WMD −2.90, 95% CI: −5.30 to −0.51), fat mass (WMD −1.52, 95% CI: −2.30 to −0.75), insulin (SMD −0.72, 95% CI: −1.24 to −0.21), total cholesterol (WMD −9.44, 95% CI: −13.62 to −5.27), low-density lipoprotein cholesterol (LDL-C) (WMD −9.94, 95% CI: −13.47 to −6.41), and energy intake (WMD −174.88, 95% CI: −283.79 to −65.97) compared to CON + RT. No significant changes were observed in muscle mass, strength, or other metabolic markers. Conclusions: TRF + RT, in contrast to CON + RT, significantly improved body composition, insulin, and cholesterol levels without affecting muscle mass or strength.

Calorie restriction (CR) is a common approach to inducing negative energy balance. Recently, time-restricted feeding (TRF), which involves consuming food within specific time windows during a 24-h day, has become popular owing to its relative ease of practice and potential to aid in achieving and maintaining a negative energy balance. TRF can be implemented intentionally with CR, or TRF might induce CR simply because of the time restriction. This review focuses on summarizing our current knowledge on how TRF and continuous CR affect gut peptides that influence satiety. Based on peer-reviewed studies, in response to CR there is an increase in the orexigenic hormone ghrelin and a reduction in fasting leptin and insulin. There is likely a reduction in glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and cholecystokinin (CCK), albeit the evidence for this is weak. After TRF, unlike CR, fasting ghrelin decreased in some TRF studies, whereas it showed no change in several others. Further, a reduction in fasting leptin, insulin, and GLP-1 has been observed. In conclusion, when other determinants of food intake are held equal, the peripheral satiety systems appear to be somewhat similarly affected by CR and TRF with regard to leptin, insulin, and GLP-1. But unlike CR, TRF did not appear to robustly increase ghrelin, suggesting different influences on appetite with a potential decrease of hunger after TRF when compared with CR. However, there are several established and novel gut peptides that have not been measured within the context of CR and TRF, and studies that have evaluated effects of TRF are often short-term, with nonuniform study designs and highly varying temporal eating patterns. More evidence and studies addressing these aspects are needed to draw definitive conclusions.

This review focuses on summarizing current knowledge on how time-restricted feeding (TRF) and continuous caloric restriction (CR) affect central neuroendocrine systems involved in regulating satiety. Several interconnected regions of the hypothalamus, brainstem, and cortical areas of the brain are involved in the regulation of satiety. Following CR and TRF, the increase in hunger and reduction in satiety signals of the melanocortin system [neuropeptide Y (NPY), proopiomelanocortin (POMC), and agouti-related peptide (AgRP)] appear similar between CR and TRF protocols, as do the dopaminergic responses in the mesocorticolimbic circuit. However, ghrelin and leptin signaling via the melanocortin system appears to improve energy balance signals and reduce hyperphagia following TRF, which has not been reported in CR. In addition to satiety systems, CR and TRF also influence circadian rhythms. CR influences the suprachiasmatic nucleus (SCN) or the primary circadian clock as seen by increased clock gene expression. In contrast, TRF appears to affect both the SCN and the peripheral clocks, as seen by phasic changes in the non-SCN (potentially the elusive food entrainable oscillator) and metabolic clocks. The peripheral clocks are influenced by the primary circadian clock but are also entrained by food timing, sleep timing, and other lifestyle parameters, which can supersede the metabolic processes that are regulated by the primary circadian clock. Taken together, TRF influences hunger/satiety, energy balance systems, and circadian rhythms, suggesting a role for adherence to CR in the long run if implemented using the TRF approach. However, these suggestions are based on only a few studies, and future investigations that use standardized protocols for the evaluation of the effect of these diet patterns (time, duration, meal composition, sufficiently powered) are necessary to verify these preliminary observations.

This study assesses the feasibility of calorie restriction (CR) and time-restricted feeding (TRF) in overweight and obese cancer patients who realized little to no physical activity undergoing curative radiotherapy, structured as a prospective, interventional, non-randomized open-label clinical trial. Of the 27 participants initially enrolled, 21 patients with breast cancer were selected for analysis. The participants self-selected into two dietary interventions: TRF, comprising a sugar and saturated fat-free diet calibrated to individual energy needs consumed within an 8 h eating window followed by a 16 h fast, or CR, involving a 25% reduction in total caloric intake from energy expenditure distributed across 4 meals and 1 snack with 55% carbohydrates, 15% protein, and 30% fats, excluding sugars and saturated fats. The primary goal was to evaluate the feasibility of these diets in the specific patient group. The results indicate that both interventions are effective and statistically significant for weight loss and reducing one's waist circumference, with TRF showing a potentially stronger impact and better adherence. Changes in the LDL, HDL, total cholesterol, triglycerides, glucose and insulin were not statistically significant. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver injury, affecting around one-fourth of the general population across the world. Several important pathophysiological mechanisms underlying NAFLD include oxidative stress, inflammation, liver fibrosis, and apoptosis. Currently, therapeutic approaches are not ideal for managing NAFLD, thus new approaches and treatments are still needed. Over the last two decades, various fasting protocols have been explored to reduce body weight and improve metabolic disorders. In this review, we provide updated literature that supports fasting regimens for subjects with NAFLD and describes underlying mechanisms of action. We suggest that fasting regimens may modulate NAFLD via several mechanisms, including changes in gut microbiota, hepatic arginase, hepatic autophagy, inflammatory responses, liver functional enzymes and hepatic steatosis, fibroblast growth factors signaling, white adipose tissue browning, adipokines, circadian rhythms, lipid profiles, and body composition. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML) with an internal tandem duplication in the fms‐like tyrosine kinase receptor 3 gene (FLT3‐ITD) is associated with poor survival, and few studies have examined the impact of modifiable behaviors, such as nutrient quality and timing, in this subset of acute leukemia. Methods: The influence of diet composition (low‐sucrose and/or low‐fat diets) and timing of diet were tested in tandem with anthracycline treatment in orthotopic xenograft mouse models. A pilot clinical study to test receptivity of pediatric leukemia patients to macronutrient matched foods was conducted. A role for the circadian protein, BMAL1 (brain and muscle ARNT‐like 1), in effects of diet timing was studied by overexpression in FLT3‐ITD‐bearing AML cells. Results: Reduced tumor burden in FLT3‐ITD AML‐bearing mice was observed with interventions utilizing low‐sucrose and/or low‐fat diets, or time‐restricted feeding (TRF) compared to mice fed normal chow ad libitum. In a tasting study, macronutrient matched low‐sucrose and low‐fat meals were offered to pediatric acute leukemia patients who largely reported liking the meals. Expression of the circadian protein, BMAL1, was heightened with TRF and the low‐sucrose diet. BMAL1 overexpression and treatment with a pharmacological inducer of BMAL1 was cytotoxic to FLT3‐ITD AML cells. Conclusions: Mouse models for FLT3‐ITD AML show that diet composition and timing slows progression of FLT3‐ITD AML growth in vivo, potentially mediated by BMAL1. These interventions to enhance therapy efficacy show preliminary feasibility, as pediatric leukemia patients responded favorable to preparation of macronutrient matched meals. [ABSTRACT FROM AUTHOR]

To investigate the efficacy and feasibility of three different 8 h time-restricted eating (TRE) schedules (i.e., early, late, and self-selected) compared to each other and to a usual-care (UC) intervention on visceral adipose tissue (VAT) and cardiometabolic health in men and women. Anticipated 208 adults (50% women) aged 30–60 years, with overweight/obesity (25 ≤ BMI<40 kg/m2) and with mild metabolic impairments will be recruited for this parallel-group, multicenter randomized controlled trial. Participants will be randomly allocated (1:1:1:1) to one of four groups for 12 weeks: UC, early TRE, late TRE or self-selected TRE. The UC group will maintain their habitual eating window and receive, as well as the TRE groups, healthy lifestyle education for weight management. The early TRE group will start eating not later than 10:00, and the late TRE group not before 13:00. The self-selected TRE group will select an 8 h eating window before the intervention and maintain it over the intervention. The primary outcome is changes in VAT, whereas secondary outcomes include body composition and cardiometabolic risk factors. This study will determine whether the timing of the eating window during TRE impacts its efficacy on VAT, body composition and cardiometabolic risk factors and provide insights about its feasibility. • This study will determine whether the timing of TRE impacts its efficacy. • The study will provide evidence about the effects of TRE on ectopic fat. • Our study is powered to investigate potential sex differences in TRE effects. [ABSTRACT FROM AUTHOR]

Dysregulation of lipid metabolism is a commonly observed feature associated with metabolic syndrome and leads to the development of negative health outcomes such as obesity, diabetes mellitus, non‐alcoholic fatty liver disease, or atherosclerosis. Time‐restricted feeding/eating (TRF/TRE), an emerging dietary intervention, has been shown to promote pleiotropic health benefits including the alteration of diurnal expression of genes associated with lipid metabolism, as well as levels of lipid species. Although TRF likely induces a response in multiple organs leading to the modulation of lipid metabolism, a majority of the studies related to TRF effects on lipids have focused only on individual tissues, and furthermore there is a lack of insight into potential underlying mechanisms. In this review, we summarize the current insights regarding TRF effects on lipid metabolism and the potential mechanisms in adipose tissue, liver, skeletal muscle, and heart, and conclude by outlining possible avenues for future exploration. [ABSTRACT FROM AUTHOR]

Circadian rhythmicity optimizes the health and physiology by coordinating temporally the cellular functions, tissue functions, and behavior. These endogenously generated rhythms gets dampen with age and therefore compromise the temporal coordination. The pattern of fasting and feeding sets an external cue that profoundly influences the robustness of daily circadian rhythms. Irregular eating patterns can change the temporal coordination of physiology and metabolism leading to chronic diseases. Robust sustaining of fasting and feeding cycle, without altering nutrition quality, can reverse or prevent the chronic diseases as already depicted in an animal model. However, in humans, studies have shown that erratic pattern of eating can elevate the risk of diseases, whereas sustained fasting and feeding cycle, or prolonged overnight fasting, is correlated with protection from different cancers. Therefore, by just optimizing the external cues timing well defined eating patterns, can thus sustain a robust circadian clock, which may result in preventing many diseases and can improve the prognosis. Time-restricted feeding (TRF) is a form of intermittent fasting, comprising a longer daily fasting period. Preliminary studies report that TRF improves cardiometabolic diseases, diabetes and cancer in rodents and humans. [ABSTRACT FROM AUTHOR]

Abstract Background Accumulating evidence has suggested an oncogenic effect of diurnal disruption on cancer progression. To test whether targeting circadian rhythm by dietary strategy suppressed lung cancer progression, we adopted 6-h time-restricted feeding (TRF) paradigm to elucidate whether and how TRF impacts lung cancer progression. Methods This study used multiple lung cancer cell lines, two xenograft mouse models, and a chemical-treated mouse lung cancer model. Stable TIM-knockdown and TIM-overexpressing A549 cells were constructed. Cancer behaviors in vitro were determined by colony formation, EdU proliferation, wound healing, transwell migration, flow cytometer, and CCK8 assays. Immunofluorescence, pathology examinations, and targeted metabolomics were also used in tumor cells and tissues. mCherry-GFP-LC3 plasmid was used to detect autophagic flux. Results We found for the first time that compared to normal ad libitum feeding, 6-h TRF inhibited lung cancer progression and reprogrammed the rhythms of metabolites or genes involved in glycolysis and the circadian rhythm in tumors. After TRF intervention, only timeless (TIM) gene among five lung cancer-associated clock genes was found to consistently align rhythm of tumor cells to that of tumor tissues. Further, we demonstrated that the anti-tumor effect upon TRF was partially mediated by the rhythmic downregulation of the TIM and the subsequent activation of autophagy. Combining TRF with TIM inhibition further enhanced the anti-tumor effect, comparable to treatment efficacy of chemotherapy in xenograft model. Conclusions Six-hour TRF inhibits lung cancer progression and reshapes circadian metabolism, which is partially mediated by the rhythmic downregulation of the TIM and the subsequent upregulation of autophagy.

Ischemia-reperfusion injury (IRI) in the kidneys is a major cause of acute kidney injury (AKI). Time-restricted feeding (TRF), known for its metabolic health benefits and alleviation of various chronic diseases without calorie restriction, was investigated for its potential protective effects against IRI-induced AKI. Male C57BL/6 mice underwent unilateral IRI, with their kidneys collected after two days. For two weeks before IRI induction, the TRF group had unlimited access to standard chow but within an 8-hour feeding window during the dark cycle. The study groups were Control, TRF, IRI, and TRF + IRI. In the TRF + IRI group, tubular damage scores significantly decreased compared to the IRI group. Furthermore, the TRF + IRI mice had lower levels of phosphorylated NF-κB and fewer F4/80-positive macrophages than the IRI group. Oxidative stress markers for lipids and proteins were also notably lower in the TRF + IRI group. Additionally, TUNEL-positive tubular cells and cleaved caspase-3 expression were reduced in the TRF + IRI group. Without calorie restriction, TRF mitigated renal damage by reducing inflammation, oxidative stress, and tubular apoptosis in renal IRI. This suggests that TRF could be a promising dietary strategy to prevent IRI-induced AKI.

Liver-expressed antimicrobial peptide-2 (LEAP-2) has mutual antagonism with ghrelin, which evokes food intake under a freely fed state. Nevertheless, the impact of LEAP-2 on ghrelin under time-restricted feeding (TRF), which has benefits in the context of metabolic disease, is still unknown. This study aims to explore the impact of central administration of LEAP-2 on the ingestion behavior of rats, which was evaluated using their cumulative food intake in the TRF state. Before intracerebroventricular (ICV) administration of O-n-octanoylated ghrelin (0.1 nmol/rat), as a food-stimulatory model, the rats received various doses of LEAP-2 (0.3, 1, 3 nmol/rat, ICV). Cumulative food intake was recorded at 1, 2, 4, 8, 12, and 24 h after ICV injection under 12 h freely fed and TRF states in a light phase. In 12 h freely fed and TRF states, central administration of ghrelin alone induced feeding behavior. Pre-treatment with LEAP-2 (1 and 3 nmol/rat, ICV) suppressed ghrelin-induced food intake in a dose-dependent manner in a 12 h freely fed state instead of a TRF state, which may have disturbed the balance of ghrelin and LEAP-2. This study provides neuroendocrine-based evidence that may explain why TRF sometimes fails in fighting obesity/metabolic dysfunction-associated steatotic liver disease in clinics.

Abstract Disruptions to circadian rhythm may be implicated in the pathogenesis of metabolic syndrome (Met‐S). For example, eating during an extended period of the day may negatively impact the circadian rhythms governing metabolic control, contributing, therefore, to Met‐S and associated end‐organ damage. Accordingly, time‐restricted eating (TRE)/feeding (TRF) is gaining popularity as a dietary intervention for the treatment and prevention of Met‐S. To date, no studies have specifically examined the impact of TRE/TRF on the renal consequences of Met‐S. The proposed study seeks to use a model of experimental Met‐S‐associated kidney disease to address this knowledge gap, disambiguating therein the effects of calorie restriction from the timing of food intake. Spontaneously hypertensive rats will consume a high‐fat diet (HFD) for 8 weeks and then be allocated by stratified randomisation according to albuminuria to one of three groups. Rats will have free 24‐h access to HFD (Group A), access to HFD during the scheduled hours of darkness (Group B) or access to HFD provided in the form of two rations, one provided during the light phase and one provided during the dark phase, equivalent overall in quantity to that consumed by rats in Group B (Group C). The primary outcome measure will be a change in albuminuria. Changes in food intake, body weight, blood pressure, glucose tolerance, fasting plasma insulin, urinary excretion of C‐peptide and renal injury biomarkers, liver and kidney histopathology and inflammation, and fibrosis‐related renal gene expression will be assessed as secondary outcomes.

Circadian rhythm (CR) is an intrinsic process that changes in a cycle of approximately 24h/day to maintain body homeostasis. It is mainly controlled by the central command through the suprachiasmatic nucleus, and modern society features can disturb the central CR, contributing to various diseases. Recent studies have provided evidence that extrinsic factors, such as regular physical activity (RPA) and timerestricted feeding (TRF), can also alter the CR peripherally, emphasizing RPA and TRF as the non-therapeutic methods for circadian misalignment (CM). Therefore, this review scrutinizes the regulatory mechanism of CR and summarizes the relationships between CM and various diseases. In addition, by reviewing studies investigating the prevention or improvement of CM via RPA and TRF, the value of circadian biology research that can directly affect health, physical function, and lifespan is summarized. By introducing the scientific evidence for RPA and TRF to maintain and improve CR, we tried to emphasize the importance of regular exercise and healthy eating habits to people in the modern world who have difficulty maintaining CR.

Purpose: Intermittent fasting (IF), describes a variety of diets that the individual is exposed to intermittent periods of fasting and refeeding. The present study was designed to compare the three most popular intermittent fasting methods in high-fat-diet-induced obese mice. Methods: 50 male C57BL/6 mice were divided into Normal Control (CN), High-Fat Control (CH), IF1 (Alternate Day Fasting), IF2 (Time-Restricted Feeding), IF3 (5:2 Diet) diets. In the first phase of the study, the mice were fed ad libitum either with a 54% Calorie high-fat (CH, IF1, IF2, IF3) or standard CHOW (CN) for 8 weeks. Then, in the intervention phase, the IF groups were fasted for four weeks based on their fasting protocol. At the end of the study, the mice fasting blood, liver and fat tissue samples were biochemically and pathologically assessed. Results: The weight loss during the fasting period in IF1 and IF2 groups was significantly greater than CH. The epididymal fat pad weight was significantly lower in IF2 and IF3 compared to CH. The serum Triglyceride was significantly greater in CH than in the CN group. The tissue injury scores of the high-fat-diet groups were significantly greater than CN. Also, the tissue injury score was greater in IF1 group compared to the high-fat control group. Conclusion: All of the fasting protocols can prompt acceptable energy restriction and the ADF and TRF protocols can significantly cause weight loss. Also, the TRF and 5:2 Diets can lower the visceral adiposity. However further human studies focusing on dietary adherence seem necessary.

IntroductionObesity is prevalent with the adult population in the United States. Energy-dense diets and erratic eating behavior contribute to obesity. Time-restricted eating is a dietary strategy in humans that has been advanced to reduce the propensity for obesity. We hypothesized that time-restricted feeding (TRF) would improve metabolic flexibility and normalize metabolic function in adult mice with established excess adiposity.MethodsMale C57BL/6NHsd mice were initially fed a high-fat diet (HFD) for 12 weeks to establish excess body adiposity, while control mice were fed a normal diet. Then, the HFD-fed mice were assigned to two groups, either ad libitum HFD or TRF of the HFD in the dark phase (12 h) for another 12 weeks.Results and discussionEnergy intake and body fat mass were similar in TRF and HFD-fed mice. TRF restored rhythmic oscillations of respiratory exchange ratio (RER), which had been flattened by the HFD, with greater RER amplitude in the dark phase. Insulin sensitivity was improved and plasma cholesterol and hepatic triacylglycerol were decreased by TRF. When compared to HFD, TRF decreased transcription of circadian genes Per1 and Per2 and genes encoding lipid metabolism (Acaca, Fads1, Fads2, Fasn, Scd1, and Srebf1) in liver. Metabolomic analysis showed that TRF created a profile that was distinct from those of mice fed the control diet or HFD, particularly in altered amino acid profiles. These included aminoacyl-tRNA-biosynthesis, glutathione metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis pathways. In conclusion, TRF improved metabolic function in adult mice with excess adiposity. This improvement was not through a reduction in body fat mass but through the restoration of metabolic flexibility.

ABSTRACTWith the drive of the endogenous circadian clock and external cues such as feeding behavior, the microbial community generates rhythmic oscillations in composition and function. Microbial oscillations are crucial in orchestrating host metabolic homeostasis during the predictable 24-hour diurnal cycle. A time-restricted feeding (TRF) regimen is a promising dietary strategy to optimize energy utilization, alleviate metabolic syndrome and reinforce microbial cyclical fluctuations. However, the causative relationship between reinforced microbial rhythmicity and TRF-induced metabolic improvement remains elusive. In this study, we corroborated that the TRF regimen notably alleviated obesity and nonalcoholic steatohepatitis (NASH) with reinstated rhythmicity of genera such as Lactobacillus, Mucispirillum, Acetatifactor, and Lachnoclostridium. The reshaped microbial oscillations correlate with cyclical fluctuations in intestinal amino acids. Furthermore, fecal microbiota transplantation (FMT) indicated that only the TRF feeding phase-derived microbiota, but not the TRF fasting phase-derived microbiota, could protect mice from NASH and reinstate microbial rhythmicity, confirming that the microbiota improved NASH in a time-of-day-specific manner. The unique role of the TRF-feeding phase-derived microbiota was accompanied by regulation of the serotonergic synapse pathway and rejuvenation of the microbial production of indole derivatives. Our results revealed the discrepant characteristics between the feeding and fasting phases and the time-of-day-specific configuration of microbiota functionality in the TRF regimen.