Time-restricted Feeding Regimen Research Articles

Time-restricted feeding improves aortic endothelial relaxation by enhancing mitochondrial function and attenuating oxidative stress in aged mice

Age-related endothelial dysfunction is a pivotal factor in the development of cardiovascular diseases, stemming, at least in part, from mitochondrial dysfunction and a consequential increase in oxidative stress. These alterations are central to the decline in vascular health seen with aging, underscoring the urgent need for interventions capable of restoring endothelial function for preventing cardiovascular diseases. Dietary interventions, notably time-restricted feeding (TRF), have been identified for their anti-aging effects on mitochondria, offering protection against age-associated declines in skeletal muscle and other organs. Motivated by these findings, our study aimed to investigate whether TRF could similarly exert protective effects on endothelial health in the vasculature, enhancing mitochondrial function and reducing oxidative stress. To explore this, 12-month-old C57BL/6 mice were placed on a TRF diet, with food access limited to a 6-h window daily for 12 months. For comparison, we included groups of young mice and age-matched controls with unrestricted feeding. We evaluated the impact of TRF on endothelial function by measuring acetylcholine-induced vasorelaxation of the aorta. Mitochondrial health was assessed using fluororespirometry, and vascular reactive oxygen species (ROS) production was quantified with the redox-sensitive dye dihydroethidium. We also quantified 4-hydroxynonenal (4-HNE) levels, a stable marker of lipid peroxidation, in the aorta using ELISA. Our findings demonstrated that aged mice on a standard diet exhibited significant impairments in aortic endothelial relaxation and mitochondrial function, associated with elevated vascular oxidative stress. Remarkably, the TRF regimen led to substantial improvements in these parameters, indicating enhanced endothelial vasorelaxation, better mitochondrial function, and reduced oxidative stress in the aortas of aged mice. This investigation establishes a vital foundation, paving the way for subsequent clinical research aimed at exploring the cardiovascular protective benefits of intermittent fasting.

Time-Restricted Feeding Mitigates Age-Related Cognitive Decline: Impacts on Neurovascular Coupling and Blood-Brain Barrier

Vascular cognitive impairment (VCI) and age-related cognitive decline are mediated by alterations in microvascular function, cerebral blood flow (CBF), neurovascular coupling (NVC) responses and blood-brain barrier (BBB) permeability. The pathogenesis of VCI can be influenced by lifestyle factors like exercise, nutrition, and dietary habits. Time-restricted feeding (TRF) offers an accessible intervention that can be employed during aging. This study is aimed at investigating the cerebromicrovascular effects of TRF on NVC responses and BBB integrity in aged mice to explore potential novel interventions against the age-related loss of cognitive function. We hypothesized that TRF would improve NVC responses and BBB integrity during aging to prevent age-related cognitive decline. To test this hypothesis, 18-month-old C57BL/6 mice were placed on TRF regimen for 6 months, where they received ad libitum feeding for 6 hours each day. 6- and 24-month-old mice fed 24 hours/day ad libitum were used as controls. All three groups were subjected to cognitive tests including radial-arms water maze (RAWM). NVC was assessed by measuring CBF using last speckle contrast imaging while performing contralateral whisker stimulation, and BBB integrity was measured through extravasation of tracers in various sizes using intravital two-photon imaging. We found that aged mice had significant impairment in NVC responses. 6 months of TRF improved BBB integrity and rescued NVC responses, and significantly improved learning and spatial memory. This study emphasizes the importance of maintaining cerebromicrovascular integrity to promote healthy brain aging and cognitive health. The establishment of the mechanisms by which TRF exerts benefits during aging provides pertinent information to the future development of therapeutic strategies to prevent VCI. Stephenson Cancer Center, National Institute of Aging R03 AG070479, American Heart Association. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Age-Related Vascular Mitochondrial Dysfunction Is Ameliorated by Time-Restricted Feeding Intervention

Endothelial dysfunction constitutes a hallmark of vascular aging that can have serious implications for disease risk. In addition, aging is associated with mitochondrial dysfunction, which can lead to increased oxidative stress and create associated damages. Time-restricted feeding (TRF) is a dietary intervention known to have many benefits on age-related disease risk. The objective of this study is to elucidate the effects of TRF upon endothelial mitochondrial function of aorta during aging. We hypothesized that TRF protects the aorta from age-related endothelial mitochondrial dysfunction. Adult C57BL/6 mice underwent TRF regimen, including six hours of ad libitum feeding daily. Young and age-matched control mice were fed ad libitum. After 12 months of TRF, wire myography was performed on aorta tissue as a measure of endothelial function. The aorta received pharmacological treatments to induce contraction, and dose-dependent dilation was quantified. For the first time, simultaneous measurement of reactive oxygen species (ROS) and oxygen consumption were completed in aorta tissue using Oroboros O2K Fluorespirometry. Dihydroethidium (DHE) fluorescent staining of ROS in aorta tissue was used to validate ROS measurements from O2K. Serum ketone body levels related to metabolic switching and relevant to mitochondrial biogenesis were determined. TRF improved endothelial-dependent dilation of aorta tissue, representing the intervention’s protection of endothelial function in aging. Aged TRF mice had greater oxygen consumption and less ROS in aorta tissue than age-matched control mice, indicating improved vascular mitochondrial function after TRF intervention. Aged TRF mice had elevated serum levels of ketone bodies involved in mitochondrial biogenesis. This supports the hypothesis that age-related changes in vascular mitochondrial health are alleviated by TRF. The knowledge gained from this study is relevant to understanding the mechanisms of age-related vascular dysfunction. Stephenson Cancer Center, National Institute of Aging R03 AG070479, American Heart Association. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

β-Hydroxybutyrate Recapitulates the Beneficial Effects of Time-Restricted Feeding and Periodic Fasting in Multiple Rodent Models of Polycystic Kidney Disease

Polycystic kidney disease is a monogenic disease caused predominantly by mutations in the PKD1 or PKD2 genes. These mutations result in the formation of large fluid-filled cysts derived from kidney epithelial cells that slowly replace functional healthy tissue. Affected kidneys rely heavily on glycolysis to meet energy demands, and is accompanied by a reduction in fatty acid oxidation and mitochondrial function. We previously reported that interventions inducing a state of ketosis, including caloric restriction, time-restricted feeding (TRF), ketogenic diet, extended fasting, and ketone supplementation, ameliorate or reverse polycystic kidney disease progression in multiple animal models. To elaborate on the capability of ketosis to alter disease progression, we compared, head-to-head, the effects of a daily 16:8 TRF regimen to periodic 48-hour fasting (PF) in both juvenile and adult Cy/+ rats. We found that alternative fasting interventions prevent juvenile disease progression and partially reverse established kidney disease in adults. Further, to test our hypothesis that an increase in β-hydroxybutyrate (BHB) may mediate these beneficial effects, we administered BHB to adult Cy/+ rats and stereospecific isomers to two orthologous mouse models of PKD ( P kd1RC/RC, Pkd1-Ksp:Cre). BHB recapitulates the effects of fasting in these models independent of stereoisomer, reducing mTORC1 signaling, increasing GSK-3β phosphorylation, expression and translocation of Nuclear factor erythroid 2-related factor 2 (Nrf2) in cystic epithelia, and subsequent downstream targets of Nrf2. These findings extend and expand our previous report on the beneficial effects of ketosis on cystic disease progression and suggest that ketogenic metabolic interventions and BHB supplementation are capable of metabolic reprogramming in polycystic kidney disease. This work was supported by grants from the NIH (Grants R01DK109563, R01DK124895) and the US Department of Defense (Grant W81XWH2010827) to T.W., and gifts from the Amy P. Goldman Foundation and the Jarrett Family Fund to University of California, Santa Barbara, to support the work of T.W. The MRL Shared Experimental Facilities are supported by the MRSEC Program of the NSF under Award No. DMR 1720256; a member of the NSF-funded Materials Research Facilities Network (www.mrfn.org). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Nav1.8-expressing neurons control daily oscillations of food intake, body weight and gut microbiota in mice.

Recent evidence suggests a role of sensory neurons expressing the sodium channel Nav1.8 on the energy homeostasis control. Using a murine diphtheria toxin ablation strategy and ad libitum and time-restricted feeding regimens of control or high-fat high-sugar diets, here we further explore the function of these neurons on food intake and on the regulation of gastrointestinal elements transmitting immune and nutrient sensing.The Nav1.8+ neuron ablation increases food intake in ad libitum and time-restricted feeding, and exacerbates daily body weight variations. Mice lacking Nav1.8+ neurons show impaired prandial regulation of gut hormone secretion and gut microbiota composition, and altered intestinal immunity.Our study demonstrates that Nav1.8+ neurons are required to control food intake and daily body weight changes, as well as to maintain physiological enteroendocrine and immune responses and the rhythmicity of thegut microbiota, which highlights the potential of Nav1.8+ neurons to restore energy balance in metabolic disorders.

Transient anticonvulsant effects of time-restricted feeding in the 6-Hz mouse model

IntroductionIntermittent fasting enhances neural bioenergetics, is neuroprotective, and elicits antioxidant effects in various animal models. There are conflicting findings on seizure protection, where intermittent fasting regimens often cause severe weight loss resembling starvation which is unsustainable long-term. Therefore, we tested whether a less intensive intermittent fasting regimen such as time-restricted feeding (TRF) may confer seizure protection. MethodsMale CD1 mice were assigned to either ad libitum-fed control, continuous 8 h TRF, or 8 h TRF with weekend ad libitum food access (2:5 TRF) for one month. Body weight, food intake, and blood glucose levels were measured. Seizure thresholds were determined at various time points using 6-Hz and maximal electroshock seizure threshold (MEST) tests. Protein levels and mRNA expression of genes, enzyme activity related to glucose metabolism, as well as mitochondrial dynamics were assessed in the cortex and hippocampus. Markers of antioxidant defence were evaluated in the plasma, cortex, and liver. ResultsBody weight gain was similar in the ad libitum-fed and TRF mouse groups. In both TRF regimens, blood glucose levels did not change between the fed and fasted state and were higher during fasting than in the ad libitum-fed groups. Mice in the TRF group had increased seizure thresholds in the 6-Hz test on day 15 and on day 19 in a second cohort of 2:5 TRF mice, but similar seizure thresholds at other time points compared to ad libitum-fed mice. Continuous TRF did not alter MEST seizure thresholds on day 28. Mice in the TRF group showed increased maximal activity of pyruvate dehydrogenase in the cortex, which was accompanied by increased protein levels of mitochondrial pyruvate carrier 1 in the cortex and hippocampus. There were no other major changes in protein or mRNA levels associated with energy metabolism and mitochondrial dynamics in the brain, nor markers of antioxidant defence in the brain, liver, or plasma. ConclusionsBoth continuous and 2:5 TRF regimens transiently increased seizure thresholds in the 6-Hz model at around 2 weeks, which coincided with stability of blood glucose levels during the fed and fasted periods. Our findings suggest that the lack of prolonged anticonvulsant effects in the acute electrical seizure models employed may be attributed to only modest metabolic and antioxidant adaptations found in the brain and liver. Our findings underscore the potential therapeutic value of TRF in managing seizure-related conditions.

PROLONGED DAILY FASTING TIMES ARE BEST WHEN COMBINED WITH CALORIE RESTRICTION FOR HEALTH AND SURVIVAL

Abstract Emerging new evidence highlights the importance of prolonged daily fasting periods for the health and survival benefits of calorie restriction (CR) and time-restricted feeding (TRF) in male mice; however, little is known about the impact of these feeding regimens in females. Using a carousel feeder system that enables controlling the duration, amount, and timing of food availability, we show that mice on CR had a robust physiological response and decreased progression of malignant neoplasms and severity of inflammatory diseases in the lung compared to TRF. CR is associated with a unique serum metabolomics signature in overnight-fasted animals compared to TRF. The systemic impact of CR and TRF regimens measured from covariation of serum metabolites with energetics and healthspan metrics indicates that daytime (rest-phase) feeding with prolonged fasting periods initiated late in life confers greater benefits when combined with an imposed lower energy intake.

Gut microbes modulate (p)ppGpp during a time-restricted feeding regimen.

Mammals do not eat continuously, instead concentrating their feeding to a restricted portion of the day. This behavior presents the mammalian gut microbiota with a fluctuating environment with consequences for host-microbiome interaction, infection risk, immune response, drug metabolism, and other aspects of health. We demonstrate that in mice, gut microbes elevate levels of an intracellular signaling molecule, (p)ppGpp, during the fasting phase of a time-restricted feeding regimen. Disabling this response in a representative human gut commensal species significantly reduces colonization during this host-fasting phase. This response appears to be general across species and conserved across mammalian gut communities, highlighting a pathway that allows healthy gut microbiomes to maintain stability in an unstable environment.

Resynchronized rhythmic oscillations of gut microbiota drive time-restricted feeding induced nonalcoholic steatohepatitis alleviation

ABSTRACT With 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.

“Effect of time-restricted feeding on high-fat diet-induced metabolic dysfunction in Drosophila melanogaster”

BackgroundMetabolic alterations associated with obesity have been related to chronodisruption i.e., the desynchronization of molecular clocks that regulate circadian rhythms. The search for tools that improve the dietary treatment of obesity has recently focused on behaviors related to chronodisruption, and intermittent fasting is increasingly gaining interest. Studies in animal models have identified the benefits of time-restricted feeding (TRF) on metabolic alterations associated with changes in circadian rhythms induced by a high-fat diet. We aimed to evaluate the effect of TRF in flies with metabolic damage and chronodisruption. MethodsUsing high-fat diet fed Drosophila melanogaster as a model of metabolic damage and chronodisruption, we determined the impact of 12-h TRF on metabolic and molecular markers. Flies with metabolic dysfunction were switched to a control diet and randomly assigned to Ad libitum or a TRF regimen for seven days. We evaluated total triglyceride content, glycemia, weight, and 24 h mRNA expression rhythms of Nlaz (insulin resistance marker), clock genes (circadian rhythm molecular markers), and the neuropeptide Cch-amide2. ResultsFlies with metabolic damage that received TRF showed lower total triglyceride content, Nlaz expression, circulating glucose, and weight compared to Ad libitum. We observed the recovery of some of the high-fat diet-induced alterations in the amplitude of the circadian rhythm, particularly in the peripheral clock. ConclusionsTRF produced a partial reversal of metabolic dysfunction and chronodisruption of circadian cycles. General significanceTRF could be a useful tool to help to ameliorate metabolic and chronobiologic damage induced by a high-fat diet.

Depot-Dependent Impact of Time-Restricted Feeding on Adipose Tissue Metabolism in High Fat Diet-Induced Obese Male Mice

Time-restricted feeding (TRF) is known to be an effective strategy for weight loss and metabolic health. TRF's effect on metabolism is complex and likely acts on various pathways within multiple tissues. Adipose tissue plays a key role in systemic homeostasis of glucose and lipid metabolism. Adipose tissue dysregulation has been causally associated with metabolic disorders in obesity. However, it is largely unknown how TRF impacts metabolic pathways such as lipolysis, lipogenesis, and thermogenesis within different in adipose tissue depots in obesity. To determine this, we conducted a 10-week TRF regimen in male mice, previously on a long-term high fat diet (HFD) and subjected the mice to TRF of a HFD for 10 h per day or ad libitum. The TRF regimen showed reduction in weight gain. TRF restored HFD-induced impairment of adipogenesis and increased lipid storage in white adipose tissues. TRF also showed a depot-dependent effect in lipid metabolism and restored ATP-consuming futile cycle of lipogenesis and lipolysis that is impaired by HFD within epididymal adipose tissue, but not inguinal fat depot. We demonstrate that TRF may be a beneficial option as a dietary and lifestyle intervention in lowering bodyweight and improving adipose tissue metabolism.

Abstract 094: Bmal1 Is Necessary For Food-Based Entrainment Of Blood Pressure And Temperature Rhythms In The Rat

Blood pressure (BP) follows a circadian rhythm, changing throughout the day. This change is crucial for cardiovascular health and in patient populations, as loss of these rhythms are associated with increased mortality and morbidity. Though BP rhythms have been recognized as important, the factors that control and entrain them are not well-described. Since the molecular clock is ubiquitously expressed in all cells and required for many circadian processes, we tested the hypothesis that the molecular clock contributes to the timing of BP rhythms in rats. Male and female rats with whole body loss of brain and muscle ARNTL-like protein ( Bmal1 ) and wild type (WT) controls (Sprague-Dawley background) were instrumented with telemeters in the abdominal aorta and placed in 12:12h light dark cycle (LD) to measure BP and core body temperature (TMP). Next, animals were placed in constant darkness (DD) for four weeks and then placed on a 12-hour time restricted feeding regimen (DD-TRF) for five days. Cosinor analysis was used to analyze BP and TMP rhythms. In a standard LD cycle, systolic BP (SBP) and TMP rhythms of both Bmal1 -knockout ( Bmal1- KO) and WT rats have similar amplitudes (2-way ANOVA for SBP and TMP, both p>0.05) which peak around zeitgeber time (ZT)18. During DD, WTs have SBP and TMP rhythms peak at circadian time (CT)19, while Bmal1 -KO rats have SBP and TMP rhythms that peak at CT 12. SBP amplitude is lower in all groups during DD compared to LD (WT males: 6.0±0.7 vs 3.8±0.7 mmHg; WT females: 7.2±0.9 vs 5.6±0.3 mmHg; KO males: 5.4±0.6 vs 4.7±0.4 mmHg; KO females: 6.2±0.6 vs 5.3±0.8 mmHg; 3-way ANOVA, p<0.05 for light cycle). During DD-TRF (CT 14.5 – 2.5), SBP and TMP rhythms of WTs peak at CT22. Bmal1 -KO rats have SBP and TMP rhythms that peak during CT16. SBP amplitude is lowered in Bmal1 -KO rats during DD-TRF compared to DD (KO males: 2.0±0.7 mmHg; KO females: 3.8±0.6 mmHg) but not in WT rats (WT males: 3.8±0.3 mmHg; WT females: 5.1±0.4 mmHg; 3-way ANOVA, p<0.05 for feeding time, sex, and feeding time*genotype). These data suggest that the molecular clock component Bmal1 is necessary for food-based entrainment of SBP and temperature rhythms in the absence of a regular light cue. Food, light cycle, and the molecular clock may all contribute to the timing and amplitude of SBP and TMP rhythms.

Time-restricted feeding during embryonic development leads to metabolic dysfunction in adult rat offspring

ObjectivesMaternal circadian eating time and frequency are associated with altered glucose metabolism during pregnancy in humans. Research on long maternal fasting intervals is inconclusive, and little is known about the effect of maternal time feeding on offspring health. Therefore, the aim of the present study is to determine whether maternal time feeding influences the metabolic status of both male and female offspring. MethodsPregnant rats were provided ad libitum access to chow diet or fed during either the light phase (LP) or dark phase (DP) during embryonic development. At the age of 150 days, glucose tolerance, lipid concentrations, and insulin secretion were determined in adult male and female offspring. ResultsBoth male and female offspring of LP and DP dams exhibited alterations in the lipid profile, and female offspring were glucose intolerant. Glucose-stimulated insulin secretion decreased in male and female offspring of LP and DP dams. Acetylcholine increased insulin secretion in male and female offspring. Islets from male and female offspring of DP dams exhibited less pronounced inhibition of insulin secretion by epinephrine, suggesting alterations in the cholinergic and adrenergic pathways in these animals. ConclusionsOur data suggest that a time-restricted feeding regimen during embryonic development could program rat offspring for metabolic dysfunction during adulthood.

Design of the OptiSurg trial: Multicenter open-label randomized controlled trial of time restricted feeding (TRF) vs regular dietary advices in patient undergoing femoral endarterectomy

Abstract Objective Vascular patients suffer some of the highest complications rates. Surprisingly, there is no uniformly accepted medical therapy to reduce complications in these patients. Time restricted feeding (TRF) is an approach that emphasizes energy intake limited to certain windows of time within the 24-hour cycle, without restrictions on any calories or macronutrients. In healthy young human, TRF improves cardio-metabolic fitness. However, there is a lack of research on TRF in patient undergoing surgery, and suffering from cardiovascular diseases. This study aims to investigate the feasibility and efficacy of a pre-operative 2-week, 10-hour TRF in patient undergoing vascular surgery. Methods The OptiSurg Study is a randomized open-label clinical trial, that plan to enroll 40 patients, undergoing elective femoral endarterectomy. Only Fontaine stage II peripheral artery disease, and a BMI ≥ 20 kg/m2 are included. Patients are randomized with a 1:1 ratio to either the control or intervention group. The control group receives diet nutritional counselling (standard of care, SOC). The intervention group receives the same SOC and a self-selected 10-hour TRE window. After the surgery, patients will be on SOC only, and followed every 3 months up to 1 year. Primary endpoint is a composite of death, myocardial infarction, stroke, and surgical re-intervention at 1 month post-operative. Blood glucose, body weight, body composition, biomarkers (neuroendocrine, inflammatory and metabolic), sleep and quality of life will also be examined. Temporal calorie intake is monitored with the smartphone application myCircadianClock preoperatively. VascuQoL-6 is used to monitor quality of life. Results 9 participants were enrolled since the start of the recruitment in February 2021, 4 were randomized in the 8 hours TRF intervention, and 5 to SOC. They all completed the study: 7 men and 2 women, age 73, 53–87 (median, min-max) years. Using the myCircadianClock app, adherence to the TRF was >90% (Figure 1). Conclusion Our preliminary experience seems to demonstrate that a 2-week TRF regimen before vascular surgery is feasible. The complete results will be disseminated through future peer-reviewed manuscripts, reports and presentations.

Organoids as Model Systems to Investigate Circadian Clock-Related Diseases and Treatments.

Circadian rhythms exist in most cell types in mammals regulating temporal organization of numerous cellular and physiological processes ranging from cell cycle to metabolism. The master clock, suprachiasmatic nucleus (SCN) in the hypothalamus, processes light input and coordinates peripheral clocks optimizing organisms’ survival and functions aligning with external conditions. Intriguingly, it was demonstrated that circadian rhythms in the mouse liver can be decoupled from the master clock under time-restricted feeding regimen when food was provided during their inactive phase. Furthermore, mouse liver showed clock-controlled gene expression even in the absence of the master clock demonstrating independent functions of peripheral clocks apart from the SCN. These findings suggest a dynamic relationship between the master and peripheral clocks and highlight potential functions of peripheral clocks independent of the master clock. Importantly, disruption of circadian rhythms correlates with numerous human ailments including cancer and metabolic diseases, suggesting that diseases may be exacerbated by disruption of circadian rhythms in the SCN and/or peripheral clocks. However, molecular mechanisms providing causative links between circadian rhythms and human diseases remain largely unknown. Recent technical advances highlighted PCS- and tissue-derived 3-dimensional organoids as in vitro organs that possess numerous applications ranging from disease modeling to drug screening. In this mini-review, we highlight recent findings on the importance and contributions of peripheral clocks and potential uses of 3D organoids investigating complex circadian clock-related diseases.

Randomized controlled trial for time-restricted eating in healthy volunteers without obesity

Time-restricted feeding (TRF) improves metabolic health. Both early TRF (eTRF, food intake restricted to the early part of the day) and mid-day TRF (mTRF, food intake restricted to the middle of the day) have been shown to have metabolic benefits. However, the two regimens have yet to be thoroughly compared. We conducted a five-week randomized trial to compare the effects of the two TRF regimens in healthy individuals without obesity (ChiCTR2000029797). The trial has completed. Ninety participants were randomized to eTRF (n=30), mTRF (n=30), or control groups (n=30) using a computer-based random-number generator. Eighty-two participants completed the entire five-week trial and were analyzed (28 in eTRF, 26 in mTRF, 28 in control groups). The primary outcome was the change in insulin resistance. Researchers who assessed the outcomes were blinded to group assignment, but participants and care givers were not. Here we show that eTRF was more effective than mTRF at improving insulin sensitivity. Furthermore, eTRF, but not mTRF, improved fasting glucose, reduced total body mass and adiposity, ameliorated inflammation, and increased gut microbial diversity. No serious adverse events were reported during the trial. In conclusion, eTRF showed greater benefits for insulin resistance and related metabolic parameters compared with mTRF. Clinical Trial Registration URL: http://www.chictr.org.cn/showproj.aspx?proj=49406.

Time-Restricted Feeding in Commercial Layer Chickens Improves Egg Quality in Old Age and Points to Lack of Adipostat Activity in Chickens.

In mammals, time-restricted feeding (TRF) with no caloric restriction provides health benefits and extends longevity, usually with a minor (∼3%) or no reduction in total food consumption. In the current study, a TRF regimen of 6 h free access to food (08:00–14:00 h) was applied to Leghorn chickens from 25 to 86 weeks of age; control birds ate freely during the light hours (06:00–20:00 h). Unexpectedly, the TRF-treated birds consumed, on average, 11.7% less food than the controls. This was manifested by an average reduction of 9.6% in body weight, 2.6-fold in visceral fat accumulation, and 6.5% in egg weight. Hen-housed egg production was reduced by 3.6% in the TRF group compared with the control, along the first 40 weeks of the follow-up (P < 0.05), and changed into a tendency of 0.7% higher egg production thereafter. Several parameters of egg quality showed significant improvement (P < 0.05) in the TRF group compared with the controls. A comparison of diurnal patterns of feed consumption revealed a higher rate of hourly consumption in the TRF group and increased consumption before dark in the control group. In conclusion, the reduced feed intake in response to the TRF treatment and loss in visceral fat accumulation supports the lack of a strong adipostat activity in chickens and different appetite regulation mechanisms compared with mammals. Therefore, future TRF studies in chickens should be adjusted by extending the ad libitum time window. The lower feed intake by the TRF-treated chickens compared with the ad libitum-fed controls seems to reduce the efficiency of egg production. Nevertheless, the improved egg quality and persistence of egg lay at the older age suggest that similarly to mammals, the TRF treatment delayed at least some of the negative impacts associated with advanced age.

Modulatory Effect of Intermittent Fasting on Adipose Tissue Inflammation: Amelioration of Cardiovascular Dysfunction in Early Metabolic Impairment.

Cardiometabolic syndrome (CMS) is a cluster of maladaptive cardiovascular, renal, thrombotic, inflammatory, and metabolic disorders. It confers a high risk of cardiovascular mortality and morbidity. CMS is triggered by major shifts in lifestyle and dietary habits with increased consumption of refined, calorie-dense diets. Evidence indicates that diet-induced CMS is linked to Adipose tissue (AT) inflammation. This led to the proposal that adipose inflammation may be involved in metabolic derangements, such as insulin resistance and poor glycemic control, as well as the contribution to the inflammatory process predisposing patients to increased cardiovascular risk. Therefore, in the absence of direct pharmacological interventions for the subclinical phase of CMS, time restricted feeding regimens were anticipated to alleviate early metabolic damage and subsequent comorbidities. These regimens, referred to as intermittent fasting (IF), showed a strong positive impact on the metabolic state of obese and non-obese human subjects and animal models, positive AT remodeling in face of overnutrition and high fat diet (HFD) consumption, and improved CV outcomes. Here, we summarize the available evidence on the role of adipose inflammation in triggering cardiovascular impairment in the context of diet induced CMS with an emphasis on the involvement of perivascular adipose tissue. As well, we propose some possible molecular pathways linking intermittent fasting to the ameliorative effect on adipose inflammation and cardiovascular dysfunction under such circumstances. We highlight a number of targets, whose function changes in perivascular adipose tissue inflammation and could be modified by intermittent fasting acting as a novel approach to ameliorate the inflammatory status.

Intermittent fasting for obesity and related disorders: unveiling myths, facts, and presumptions.

Intermittent fasting (IF) is an increasingly popular method of weight loss, as an alternative to daily caloric restriction (DCR). Several forms of IF exist, such as alternate-day fasting or time-restricted feeding regimens. Some of its proponents claim several health benefits unrelated to caloric restriction or weight loss, which rely mainly on animal models. Although several studies published in the last few years confirm that IF can be a useful and safe therapeutical option for obesity and related disorders, no superiority to conventional caloric restriction diets have emerged. There are still several questions left answered. In this Review, we discuss some of the claims, unveiling myths, facts, and presumptions about several models of IF. The focus of this article is obesity, but there is a brief discussion of the potential benefits of IF on overall human health.

Effects of time-restricted feeding in weight loss, metabolic syndrome and cardiovascular risk in obese women

BackgroundThe increasing prevalence of overweight and obesity among the worldwide population has been associated with a range of adverse health consequences such as Type 2 diabetes and cardiovascular diseases. The metabolic syndrome (MetS) is a cluster of cardiometabolic abnormalities that occur more commonly in overweight individuals. Time-restricted feeding (TRF) is a dietary approach used for weight loss and overall health. TRF may be an option for those subjects who struggle with extreme restriction diets with foods that generally do not belong to an individual's habits.ObjectiveThe purpose of this study was to determine the effect of TRF on body composition and the association of weight loss with metabolic and cardiovascular risks in obese middle-aged women.MethodsA non-randomized controlled clinical trial was performed over 3 months in obese women (TRF group, n = 20, BMI 32.53 ± 1.13 vs. Control n = 12, BMI 34.55 ± 1.20). The TRF protocol adopted was 16 h without any energy intake followed by 8 h of normal food intake.Main outcomes and measuresAnthropometric measurements, body composition, blood biomarkers, cardiovascular risk in 30 years (CVDRisk30y), and quality of life were evaluated at baseline and after the 3 months.ResultsTRF was effective in reducing weight (~ 4 kg), BMI, % of body fat (%BF), waist circumference from baseline without changes in blood biomarkers associated with MetS. TRF promoted a reduction in CVDRisk30y (12%) wich was moderately correlated with %BF (r = 0.62, n = 64, p < 0.001) and %MM (r = − 0.74, n = 64, p < 0.001).ConclusionsTRF protocol reduces body weight without changes in biomarkers related to MetS. In addition, the anthropometric evaluation that predicts %BF and %MM could be used as an approach to follow individuals engaged in the TRF regimen since they correlate with cardiovascular risk.