Complex physiology and clinical implications of time-restricted eating.

Time-restricted eating (TRE) is a dietary intervention that limits food consumption to a specific time window each day. The effect of TRE on body weight and physiological functions has been extensively studied in rodent models, which have shown considerable therapeutic effects of TRE and important interactions among time of eating, circadian biology, and metabolic homeostasis. In contrast, it is difficult to make firm conclusions regarding the effect of TRE in people because of the heterogeneity in results, TRE regimens, and study populations. In this review, we 1) provide a background of the history of meal consumption in people and the normal physiology of eating and fasting; 2) discuss the interaction between circadian molecular metabolism and TRE; 3) integrate the results of preclinical and clinical studies that evaluated the effects of TRE on body weight and physiological functions; 4) summarize other time-related dietary interventions that have been studied in people; and 4) identify current gaps in knowledge and provide a framework for future research directions.

The 5:2 diet does not increase adult hippocampal neurogenesis or enhance spatial memory in mice.

New neurones are generated throughout life in the mammalian brain in a process known as adult hippocampal neurogenesis (AHN). Since this phenomenon grants a high degree of neuroplasticity influencing learning and memory, identifying factors that regulate AHN may be important for ameliorating age-related cognitive decline. Calorie restriction (CR) has been shown to enhance AHN and improve memory, mediated by the stomach hormone, ghrelin. Intermittent fasting (IF), a dietary strategy offering more flexibility than conventional CR, has also been shown to promote aspects of AHN. The 5:2 diet is a popular form of IF; however, its effects on AHN are not well characterised. To address this, we quantified AHN in adolescent and adult wild-type and ghrelin-receptor-deficient mice following 6 weeks on a 5:2 diet. We report an age-related decline in neurogenic processes. However, the 5:2 diet does not increase AHN nor enhance memory performance, suggesting that this specific form of IF is ineffective in promoting brain plasticity to support learning.

Time-Restricted Feeding Reduces Atherosclerosis in LDLR KO Mice but Not in ApoE Knockout Mice.

BACKGROUND: Dyslipidemia increases cardiovascular disease risk, the leading cause of death worldwide. Under time-restricted feeding (TRF), wherein food intake is restricted to a consistent window of <12 hours, weight gain, glucose intolerance, inflammation, dyslipidemia, and hypercholesterolemia are all reduced in mice fed an obesogenic diet. LDLR (low-density lipoprotein receptor) mutations are a major cause of familial hypercholesterolemia and early-onset cardiovascular disease. METHODS: We subjected benchmark preclinical models, mice lacking LDLR-knockout or ApoE knockout to ad libitum feeding of an isocaloric atherogenic diet either ad libitum or 9 hours TRF for up to 13 weeks and assessed disease development, mechanism, and global changes in hepatic gene expression and plasma lipids. In a regression model, a subset of LDLR-knockout mice were ad libitum fed and then subject to TRF. RESULTS: TRF could significantly attenuate weight gain, hypercholesterolemia, and atherosclerosis in mice lacking the LDLR-knockout mice under experimental conditions of both prevention and regression. In LDLR-knockout mice, increased hepatic expression of genes mediating ß-oxidation during fasting is associated with reduced VLDL (very-low-density lipoprotein) secretion and lipid accumulation. Additionally, increased sterol catabolism coupled with fecal loss of cholesterol and bile acids contributes to the atheroprotective effect of TRF. Finally, TRF alone or combined with a cholesterol-free diet can reduce atherosclerosis in LDLR-knockout mice. However, mice lacking ApoE, which is an important protein for hepatic lipoprotein reuptake do not respond to TRF. CONCLUSIONS: In a preclinical animal model, TRF is effective in both the prevention and regression of atherosclerosis in LDLR knockout mice. The results suggest TRF alone or in combination with a low-cholesterol diet can be a lifestyle intervention for reducing cardiovascular disease risk in humans.

Reduced liver damage and fibrosis with combined SCD Probiotics and intermittent fasting in aged rat.

This study aimed to examine the impact of SCD Probiotics supplementation on liver biomolecule content and histological changes during a 30-day intermittent fasting (IF) program in 24-month-old male Sprague-Dawley rats. Rats underwent 18-h daily fasting and received 1 × 108 CFU of SCD Probiotics daily. Liver tissue biomolecules were analysed using FTIR Spectroscopy, LDA, and SVM techniques, while histopathological evaluations used Haematoxylin and eosin and Masson trichrome-stained tissues. Blood samples were collected for biochemical analysis. Gross alterations in the quantity of biomolecules were observed with individual or combined treatments. LDA and SVM analyses demonstrated a high accuracy in differentiating control and treated groups. The combination treatments led to the most significant reduction in cholesterol ester (1740 cm-1 ) and improved protein phosphorylation (A1239 /A2955 and A1080 /A1545 ) and carbonylation (A1740 /A1545 ). Individually, IF and SCD Probiotics were more effective in enhancing membrane dynamics (Bw2922 /Bw2955 ). In treated groups, histological evaluations showed decreased hepatocyte degeneration, lymphocyticinfiltration, steatosis and fibrosis. Serum ALP, LDH and albumin levels significantly increased in the SCD Probiotics and combined treatment groups. This study offers valuable insights into the potential mechanisms behind the beneficial effects of IF and SCD Probiotics on liver biomolecule content, contributing to the development of personalized nutrition and health strategies.

Exploring the therapeutic potential of plasma from intermittent fasting and untreated rats on aging-induced liver damage.

This research aims to investigate the effects of plasma from 12-month-old intermittently fasting rats (IFpls) and untreated rats (Npls) on the liver biomolecules and histological changes in 24-month-old male Sprague-Dawley rats. Fasting rats underwent an 18-h daily fasting period and a 6-h feeding window for 35 days. The plasma was administered bi-daily, and blood samples were examined for specific liver biomolecules. Fourier transform infrared (FTIR) spectroscopy and linear discriminant analysis (LDA) was used to identify molecular profiles. Liver sections were stained for histopathological evaluation, and the expression levels of Notch signalling pathway components were assessed. Distinct molecular profiles were identified across liver biomolecules, lipids, proteins and nucleic acids with high accuracy. Notably, IFpls was found to protect against hepatic instability, microvesicular steatosis and liver fibrosis by decreasing lymphatic infiltration density and Notch pathway expression levels. Both treatments reduced protein oxidation and carbonylation, with Npls showing a pronounced decrease in protein oxidation. Furthermore, Npls increased protein conformation and glycogen/phosphate content, while IFpls increased glucose/protein content. Both IFpls and Npls induce substantial and unique alterations in liver biomolecules. IFpls offers a protective effect on various liver conditions, while Npls exhibits promising results in reducing protein oxidation and altering biomolecule content. These findings offer valuable insights for future research and potential therapeutic approaches.

Supplementing probiotics during intermittent fasting proves more effective in restoring ileum and colon tissues in aged rats.

This study aimed to explore the impact of SCD Probiotics supplementation on biomolecule profiles and histopathology of ileum and colon tissues during a 30-day intermittent fasting (IF) program. Male Sprague-Dawley rats, aged 24 months, underwent 18-h daily fasting and received 3 mL (1 × 108 CFU) of SCD Probiotics. The differences in biomolecule profiles were determined using FTIR Spectroscopy and two machine learning techniques, Linear Discriminant Analysis (LDA) and Support Vector Machine (SVM), which showed significant differences with high accuracy rates. Spectrochemical bands indicating alterations in lipid, protein and nucleic acid profiles in both tissues. The most notable changes were observed in the group subjected to both IF and SCD Probiotics, particularly in the colon. Both interventions, individually and in combination, decreased protein carbonylation levels. SCD Probiotics exerted a more substantial impact on membrane dynamics than IF alone. Additionally, both IF and SCD Probiotics were found to have protective effects on intestinal structure and stability by reducing mast cell density and levels of TNF-α and NF-κB expression in ileum and colon tissues, thus potentially mitigating age-related intestinal damage and inflammation. Furthermore, our results illustrated that while IF and SCD Probiotics individually instigate unique changes in ileum and colon tissues, their combined application yielded more substantial benefits. This study provides evidence for the synergistic potential of IF and SCD Probiotics in combating age-related intestinal alterations.

Circadian-Dependent Intermittent Fasting Influences Ischemic Tolerance and Dendritic Spine Remodeling.

BACKGROUND: Preconditioning by intermittent fasting is linked to improved cognition and motor function, and enhanced recovery after stroke. Although the duration of fasting was shown to elicit different levels of neuroprotection after ischemic stroke, the impact of time of fasting with respect to the circadian cycles remains unexplored. METHODS: Cohorts of mice were subjected to a daily 16-hour fast, either during the dark phase (active-phase intermittent fasting) or the light phase (inactive-phase intermittent fasting) or were fed ad libitum. Following a 6-week dietary regimen, mice were subjected to transient focal cerebral ischemia and underwent behavioral functional assessment. Brain samples were collected for RNA sequencing and histopathologic analyses. RESULTS: Active-phase intermittent fasting cohort exhibited better poststroke motor and cognitive recovery as well as reduced infarction, in contrast to inactive-phase intermittent fasting cohort, when compared with ad libitum cohort. In addition, protection of dendritic spine density/morphology and increased expression of postsynaptic density protein-95 were observed in the active-phase intermittent fasting. CONCLUSIONS: These findings indicate that the time of daily fasting is an important factor in inducing ischemic tolerance by intermittent fasting.

A detective story of intermittent fasting effect on immunity.

Intermittent fasting (IF) refers to periodic fasting routines, that caloric intake is minimized not by meal portion size reduction but by intermittently eliminating ingestion of one or several consecutive meals. IF can instigate comprehensive and multifaceted alterations in energy metabolism, these metabolic channels may aboundingly function as primordial mechanisms that interface with the immune system, instigating intricate immune transformations. This review delivers a comprehensive understanding of IF, paying particular attention to its influence on the immune system, thus seeking to bridge these two research domains. We explore how IF effects lipid metabolism, hormonal levels, circadian rhythm, autophagy, oxidative stress, gut microbiota, and intestinal barrier integrity, and conjecture about the mechanisms orchestrating the intersect between these factors and the immune system. Moreover, the review includes research findings on the implications of IF on the immune system and patients burdened with autoimmune diseases.

Current perspective on circadian function of the kidney.

Behavior and function of living systems are synchronized by the 24-h rotation of the Earth that guides physiology according to time of day. However, when behavior becomes misaligned from the light-dark cycle, such as in rotating shift work, jet lag, and even unusual eating patterns, adverse health consequences such as cardiovascular or cardiometabolic disease can arise. The discovery of cell-autonomous molecular clocks expanded interest in regulatory systems that control circadian physiology including within the kidney, where function varies along a 24-h cycle. Our understanding of the mechanisms for circadian control of physiology is in the early stages, and so the present review provides an overview of what is known and the many gaps in our current understanding. We include a particular focus on the impact of eating behaviors, especially meal timing. A better understanding of the mechanisms guiding circadian function of the kidney is expected to reveal new insights into causes and consequences of a wide range of disorders involving the kidney, including hypertension, obesity, and chronic kidney disease.

Intermittent fasting increases fat oxidation and promotes metabolic flexibility in lean mice but not obese type 2 diabetic mice.

Obesity and type 2 diabetes (T2D) are associated with metabolic inflexibility, characterized by an impaired ability to switch between substrate storage and utilization pathways. Metabolic inflexibility during obesity is typified by lower engagement of fatty acid metabolism despite an ample supply of stored lipids. Intermittent fasting (IF) can promote metabolic flexibility. However, it is not clear how obesity and T2D alter metabolic flexibility after repeated IF. Male obese db/db and control db/+ mice were fasted for 24 hours twice a week for 10 weeks. This 5:2 IF regimen did not alter body mass, body composition, food intake, or physical activity in db/db or db/+ mice. After IF, db/db mice had lower fatty acid oxidation and higher carbohydrate oxidation in the fed state, indicating metabolic inflexibility to metabolize lipids. After IF, control db/+ mice had higher fatty acid oxidation and lower carbohydrate oxidation in the fed state, characteristic of metabolic flexibility and increased engagement of lipid metabolism. In the fasted state, IF lowered carbohydrate oxidation and increased fatty acid oxidation in control db/+ mice but not in obese db/db mice. After IF, db/db mice also had lower serum ß-hydroxybutyrate than control db/+ mice. 10 weeks of IF decreased adipocyte size in visceral adipose tissue of control db/+ mice, but this IF regimen did not change adipocyte size in obese db/db mice. Therefore, IF increases fatty acid oxidation and metabolic flexibility in lean mice, but this adaptation is absent in a mouse model of obesity and type 2 diabetes.

Intermittent fasting and high-intensity interval training do not alter gut microbiota composition in adult women with obesity.

Obesity is advancing at an accelerated pace, and yet its treatment is still an emerging field. Although studies have demonstrated the role of the microbiota in the pathogenesis of obesity, this is the first study to show the effects of intermittent fasting (IF), combined or not with exercise, and high-intensity interval training (HIIT) on the gut microbiota composition in women with obesity. Our hypothesis is that IF combined with HIIT can promote the remodeling of the composition and function of the gut microbiota. Thirty-six women with obesity, aged between 18 and 40 yr, participated in the study. They were randomly divided into three groups: 1) IF associated with HIIT group [IF + exercise group (EX), n = 15]; 2) HIIT group (EX, n = 11); and 3) IF group (IF, n = 10). Interventions took place over 8 wk, and all assessments were performed preintervention and postintervention. The HIIT circuit was performed 3 times/wk, for 25 min/session. The IF protocol was a 5:2 (2 times/wk). Multiplex analysis of inflammatory cytokines, sequencing of the 16S rRNA gene, and gas chromatography to measure fecal concentrations of short-chain fatty acids (SCFAs) were performed. This study was registered on ClinicalTrials.gov (NCT05237154). Exercise increased fecal acetate concentrations (P = 0.04), but no changes were observed in the composition and functional profile of the microbiota. The interventions did not change the composition of the microbiota, but exercise may play a modulatory role in the production of acetate. This investigation provides clinical insights into the use of IF and HIIT for women with obesity.NEW & NOTEWORTHY This is the first investigation about alternate-day fasting combined with HITT on the gut microbiota of obese women. The study contributes to the advancement of human science involving IF and HIIT, popular strategies for managing obesity. Previous evidence has explored IF in modulating the microbiota in animal models or specific populations and clinical conditions. Despite the subtle outcomes, this study has relevance and originality in the field of gut microbiota knowledge.

Is breakfast consumption detrimental, unnecessary, or an opportunity for health promotion? A review of cardiometabolic outcomes and functional food choices.

Breakfast consumption is generally considered a health-promoting habit for cardiometabolism, particularly with regard to chrononutrition. Glucose uptake is enhanced by proper insulin secretion triggered by the pancreatic clock, averting metabolic dysregulation related to insulin resistance. Breakfast skipping, in turn, is often considered a behaviour detrimental to health, in part due to putative inverse metabolic actions compared to breakfast consumption, such that breakfast skipping may promote circadian desynchrony. However, most ill health concerns about breakfast skipping are inferred from observational research, and recent well-controlled randomized clinical trials have shown benefits of breakfast skipping for cardiovascular risk factors. Accordingly, this review describes the effects of breakfast consumption versus breakfast skipping on cardiovascular risk factors (blood pressure and glycaemic and lipid indices). In addition, the view of breakfast consumption as an opportunity for functional food ingestion is considered to provide further insights into decision-making practice. Collectively, both breakfast consumption and breakfast skipping can be considered viable habits, but they depend on individual preferences, planning, and the specific foods being consumed or omitted. When consumed, breakfast should consist primarily of functional foods typical for this meal (e.g., eggs, dairy products, nuts, fruits, whole grains, coffee, tea, etc.). While breakfast consumption aligns with chrononutrition principles, breakfast skipping can contribute to a calorie deficit over time, which has the potential for widespread cardiometabolic benefits for patients with overweight/obesity. The concepts and practical considerations discussed in the present review may aid health care personnel in personalising breakfast consumption recommendations for diverse patient populations.

The effect of time of eating on cardiometabolic risk in primary and secondary prevention of cardiovascular disease.

Continuous energy restriction is currently considered the first-line dietary therapy for weight loss in individuals with obesity. Recently, interventions which alter the eating window and time of eating occasions have been explored as means to achieve weight loss and other cardiometabolic improvements such as a reduction in blood pressure, glycaemia, lipids and inflammation. It is unknown, however, whether these changes result from unintentional energy restriction or from other mechanisms such as the alignment of nutrient intake with the internal circadian clock. Even less is known regarding the safety and efficacy of these interventions in individuals with established chronic noncommunicable disease states, such as cardiovascular disease. This review examines the effects of interventions which alter both eating window and time of eating occasions on weight and other cardiometabolic risk factors in both healthy participants and those with established cardiovascular disease. We then summarise the state of existing knowledge and explore future directions of study.

Circadian alignment of food intake and glycaemic control by time-restricted eating: A systematic review and meta-analysis.

Daily rhythms of metabolic function are supported by molecular circadian clock systems that are strongly regulated by feeding and fasting. Intermittent fasting diets have been associated with weight loss and improved metabolism. However, the effects of time-restricted eating (TRE) on glycemic parameters are still under debate. In this review, we aim to systematically analyze the effects of TRE on glycemic parameters. We searched on PubMed, EMBASE, and the Cochrane Library for controlled studies in which subjects followed TRE for at least 4 weeks. 20 studies were included in the qualitative systematic review, and 18 studies (n = 1169 subjects) were included in the meta-analysis. Overall, TRE had no significant effect on fasting glucose (Hedges's g = -0.08; 95% CI:-0.31,0.16; p = 0.52), but it did reduce HbA1c levels (Hedges's g = -0.27; 95% CI: -0.47, -0.06; p = 0.01). TRE significantly reduced fasting insulin (Hedges's g = -0.40; 95% CI: -0.73,-0.08; p = 0.01) and showed a tendency to decrease HOMA-IR (Hedges's g = -0.32; 95% CI:-0.66,0.02; p = 0.06). Interestingly, a cumulative analysis showed that the beneficial effects of TRE regarding glucose levels were less apparent as studies with later TRE windows (lTRE) were being included. Indeed, a subgroup analysis of the early TRE (eTRE) studies revealed that fasting glucose was significantly reduced by eTRE (Hedges's g = -0.38; 95% CI:-0.62, -0.14; p < 0.01). Our meta-analysis suggests that TRE can reduce HbA1c and insulin levels, and that timing of food intake is a crucial factor in the metabolic benefit of TRE, as only eTRE is capable of reducing fasting glucose levels in subjects with overweight or obesity.PROSPERO registration number CRD42023405946.

Restrictive diets have a beneficial impact on dextran sodium sulfate-induced colitis in male mice.

BACKGROUND: Previously, we assessed the impact of restrictive diets, including caloric restriction (CR), intermittent fasting (IF), or fasting-mimicking diet (FMD), on a healthy gastrointestinal tract. We revealed that each of the diets shows anti-inflammatory outcomes. OBJECTIVE: The current study aimed to verify the diets' applicability in treating colitis. METHODS: We exposed a mouse model with mild chronic dextran sodium sulfate (DSS)-induced colitis to ad libitum control feeding, CR, IF, or FMD. The collected samples were analyzed for markers of inflammation. RESULTS: The diets reduced DSS-triggered increases in spleen weight and myeloperoxidase (MPO) activity. Diet intervention also influenced occludin levels, small intestine morphology, as well as cytokine and inflammatory gene expression, mainly in the mucosa of the proximal colon. The diets did not reverse DSS-enhanced gut permeability and thickening of the colon muscularis externa. Concerning inflammatory gene expression, the impact of DSS and the dietary intervention was limited to the colon as we did not measure major changes in the jejunum mucosa, Peyer's patches, and mesenteric lymph nodes. Further, rather modest changes in the concentration of intestinal bile acids were observed in response to the diets, whereas taurine and its conjugates levels were strongly affected. CONCLUSIONS: Despite the differences in the dietary protocol, the tested diets showed very similar impacts and, therefore, may be interchangeable when aiming to reduce inflammation in the colon. However, FMD showed the most consistent beneficial impact.

Length of Overnight Fasting and 6-year Weight Change in the Cancer Prevention Study-3.

BACKGROUND: Longer overnight fasting (ONF) is a potential strategy for weight control. Although promising, the evidence from large population-based studies is limited. OBJECTIVES: To examine the association of self-reported ONF duration with 3- and 6-y weight change in the American Cancer Society's Cancer Prevention Study-3 prospective cohort. METHODS: United States adult Cancer Prevention Study-3 participants completed a 24-h validated meal and snack timing and frequency grid (weekday and weekend) in 2015, from which weighted ONF hours were calculated. Participants reported body weight in 2015, 2018, and 2021. Three- and 6-y weight change (kg, and % body weight) were assessed. RESULTS: Among 104,420 mostly female (78.5%) participants aged 52.7 ± 9.5 (standard deviation) y followed for 6 y, a 1-h increase in ONF length was associated with a small but statistically significant reduction in weight gain over 3- and 6-y periods [multivariable-adjusted mean difference in % body weight = -0.02, 95% confidence interval (CI): -0.05, -0.00, P = 0.03 and -0.04, 95% CI: -0.07, -0.01, P < 0.01, respectively]. The mean difference of 6-y % reduction in weight gain was slightly greater among individuals with overweight (-0.05, 95% CI: -0.10, 0.00, P = 0.05) and obesity (-0.06, 95% CI: -0.12, 0.01, P = 0.08) compared with those with healthy body mass index (-0.03, 95% CI:-0.07, 0.01, P = 0.13) or underweight (0.16, 95% CI: -0.04, 0.36, P = 0.13, Pinteraction < 0.0001). Stronger associations were observed among those ≤55 y than 56+ (P < 0.001), and those with higher waist circumference (Pinteraction < 0.0001) but not by sex or earlier/later fasting period. CONCLUSIONS: Longer ONF was associated with slightly lower body weight in adult males and females over 6 y that was stronger among those with overweight or obesity, higher waist circumference, and those aged ≤55 y. The magnitude of weight change, although in the hypothesized direction, suggests that prolonged ONF may have modest impact on weight control over time.

Maternal intermittent fasting deteriorates offspring metabolism via suppression of hepatic mTORC1 signaling.

The metabolic benefits of intermittent fasting (IF) have been well recognized. However, limited studies have examined the relationship between long-term maternal IF before pregnancy and offspring health. In this study, a C57BL/6J mouse model of long-term IF before pregnancy was established: 4-week-old female mice were subjected to alternate-day fasting for 12 weeks and resumed normal diet after mating. Female mice in the control group were fed ad libitum. Offspring mice were weaned at 6 weeks of age and fed a normal chow diet or a 60% high-fat diet. The effects of long-term pre-pregnancy IF on offspring metabolism and its underlying mechanism were examined. We found that neonatal IF offspring weighted significantly less relevant to control mice. This difference gradually disappeared as a result of catch-up growth. In the IF offspring, adipose tissue mass was significantly increased. This alteration was associated with a considerable deterioration in glucose tolerance. No significant difference in food intake was observed. Further, lipid deposition as well as triglyceride contents in the liver were greatly increased. Maternal IF significantly decreased levels of DNA methyltransferase in the liver of offspring. DNA methylation modifications of molecules associated with the mTORC1 signaling pathway were significantly altered, leading to the significant inhibition of mTORC1 signaling. Overexpression of S6K1 activated hepatic mTORC1 signaling and reversed the metabolic dysfunction in IF offspring. In conclusion, long-term pre-pregnancy IF increases hepatic steatosis and adiposity, as well as impairs glucose metabolism in adult offspring. This occurs through DNA methylation-dependent suppression of hepatic mTORC1 signaling activity.

Dietary interventions improve diabetic kidney disease, but not peripheral neuropathy, in a db/db mouse model of type 2 diabetes.

Patients with type 2 diabetes often develop the microvascular complications of diabetic kidney disease (DKD) and diabetic peripheral neuropathy (DPN), which decrease quality of life and increase mortality. Unfortunately, treatment options for DKD and DPN are limited. Lifestyle interventions, such as changes to diet, have been proposed as non-pharmacological treatment options for preventing or improving DKD and DPN. However, there are no reported studies simultaneously evaluating the therapeutic efficacy of varying dietary interventions in a type 2 diabetes mouse model of both DKD and DPN. Therefore, we compared the efficacy of a 12-week regimen of three dietary interventions, low carbohydrate, caloric restriction, and alternate day fasting, for preventing complications in a db/db type 2 diabetes mouse model by performing metabolic, DKD, and DPN phenotyping. All three dietary interventions promoted weight loss, ameliorated glycemic status, and improved DKD, but did not impact percent fat mass and DPN. Multiple regression analysis identified a negative correlation between fat mass and motor nerve conduction velocity. Collectively, our data indicate that these three dietary interventions improved weight and glycemic status and alleviated DKD but not DPN. Moreover, diets that decrease fat mass may be a promising non-pharmacological approach to improve DPN in type 2 diabetes given the negative correlation between fat mass and motor nerve conduction velocity.

Intermittent fasting shifts the diurnal transcriptome atlas of transcription factors.

Intermittent fasting remains a safe and effective strategy to ameliorate various age-related diseases, but its specific mechanisms are not fully understood. Considering that transcription factors (TFs) determine the response to environmental signals, here, we profiled the diurnal expression of 600 samples across four metabolic tissues sampled every 4 over 24 h from mice placed on five different feeding regimens to provide an atlas of TFs in biological space, time, and feeding regimen. Results showed that 1218 TFs exhibited tissue-specific and temporal expression profiles in ad libitum mice, of which 974 displayed significant oscillations at least in one tissue. Intermittent fasting triggered more than 90% (1161 in 1234) of TFs to oscillate somewhere in the body and repartitioned their tissue-specific expression. A single round of fasting generally promoted TF expression, especially in skeletal muscle and adipose tissues, while intermittent fasting mainly suppressed TF expression. Intermittent fasting down-regulated aging pathway and upregulated the pathway responsible for the inhibition of mammalian target of rapamycin (mTOR). Intermittent fasting shifts the diurnal transcriptome atlas of TFs, and mTOR inhibition may orchestrate intermittent fasting-induced health improvements. This atlas offers a reference and resource to understand how TFs and intermittent fasting may contribute to diurnal rhythm oscillation and bring about specific health benefits.

The effects of time-restricted eating alone or in combination with probiotic supplementation in comparison with a calorie-restricted diet on endocrine and metabolic profiles in women with polycystic ovary syndrome: A randomized clinical trial.

AIM: To assess the impact of intermittent fasting, with or without probiotic supplementation, versus a calorie-restricted diet on anthropometric measures, metabolic status and gonadal variables in women with polycystic ovary syndrome (PCOS). METHODS: This is a randomized, placebo-controlled, parallel-arm clinical trial. The effects of the 14:10 early time-restricted eating (eTRE) strategy alone or combined with probiotics, on obese women with PCOS, were investigated. Participants were divided into three groups: eTRE plus probiotics (n = 30), eTRE plus placebo (n = 30) and a control group following a standard three-meal-per-day diet with daily calorie restriction (DCR) (n = 30). Over 8 weeks, various anthropometric, metabolic, menstrual and gonadal variables were assessed. RESULTS: A total of 90 individuals were included in the study, with a mean body weight of 81.4 kg, and a mean age of 30 years. Mean (standard deviation) weight loss was not different between the groups at week 8 (TRE + probiotic: -2.2 [1.6] kg vs. TRE + placebo: -2.9 [2.7] kg vs. DCR: -2.5 [1.7] kg). Results revealed that, while all three regimes led to reductions in body weight, body mass index, vascular risk indicators, hirsutism and acne scores, there were no statistically significant differences between the eTRE groups and the control group in terms of weight loss, or improvements in metabolic, menstrual and gonadal variables (P > .05). Additionally, combining probiotics with eTRE did not benefit hormonal and cardiometabolic factors (P > .05). CONCLUSIONS: The eTRE alone or eTRE plus probiotics did not result in significantly greater weight loss or improvements in metabolic, menstrual and gonadal variables compared with the standard three-meal DCR diet.