The Effects And Mechanisms Of Early And Late Time-Restricted Eating On Weight And Cardiometabolic Health In Overweight And Obese Adults

Part One Effects of Early and Late Time-Restricted Eating on Weight and Cardiometabolic Health in Overweight and Obese AdultsObjection:Due to the complex interactions between circadian biology,nutrition,and human metabolism,meal timing may be a key modulator of health outcomes.The aim of the study is to evaluate the effects of 6-h early and late time-restricted eating(TRE)on body weight and cardiometabolic health in overweight and obese adults,providing scientific evidence for the application of TRE in the prevention and treatment of overweight and obese individuals.Methods:1.Participants RecruitmentA total of 89 participants were originally recruited from Hebei Medical University via posters around campus.Among the 89 participants,26 were excluded from the study based on the inclusion criteria.A total of 63participants were randomly assigned to the control group,6-h l TRE group,or6-h eTRE group in a 1:1:1 ratio using SPSS21.0.Randomization was carried out though a stratified random sampling procedure by gender and BMI(24.0–27.9 kg/m~2/≥28.0 kg/m~2).The study was registered on the Chinese Clinical Trail Registry(Chi CTR2000039115).2.Sample SizePower calculations were performed using PASS15.0.Assuming an alpha value of 5%and 80%of power that the difference in body weight loss would be3%between the 6-h TRE intervention and control groups by week 8,17participants were required per group.We anticipated a dropout rate of 20%.Thus,we initially aimed to recruit 63 participants(n=21 per group).3.Experimental DesignThe trial comprised a 2-week baseline and an 8-week TRE intervention period.During the 2-week baseline period,all participants were required to maintain stable weight by keeping their usual diet and physical activity habits.During the 8-week intervention,the 6-h eTRE group was directed to eat ad libitum from 7:00 am to 1:00 pm daily and completely fast from 1:00 pm to7:00 am the following day.The 6-h l TRE group was directed to eat ad libitum from 12:00 pm to 6:00 pm daily and completely fast from 6:00 pm to 12:00 pm the following day.Controls were directed to maintain their eating or physical activity habits throughout the trial.In this study,anthropometric measurements and blood sampling were performed at baseline,4 and 8 weeks after the intervention.Anthropometric measurements mainly included height,weight,waist circumference,hip circumference,body composition,blood pressure,grip strength and bone mineral density.Blood samples are mainly used for biochemical testing,including glucose,blood lipid,liver and renal function.4.Dietary Intake and Physical ActivityParticipants were given a 7-day dietary surveys and physical activity measurements at baseline and at week 8 of the intervention.Participants received an SF-400A electronic compact scale and were asked to measure the weight of foods consumed.The timing of food consumption(for each beverage or food item)was also documented in the food record.The energy content of each meal was estimated using China Food Composition Database.Energy expenditure were measured using an AM-120 multi-function electronic pedometer(TANITA,Japan).Results:1.At baseline,no significant differences were observed between the 6-h eTRE,6-h l TRE,or control groups for the primary outcome measure(body weight)or any secondary outcome measure(P>0.05).2.The 6-h eTRE(-4.6%[95%CI:-5.5,-3.8])and l TRE(-3.7%[95%CI:-4.6,-2.9])resulted in greater reduction in body weight by week 8 compared with the control group(-0.2%[95%CI:-1.1,0.7]),with no difference between the intervention groups(P>0.05).3.The 6-h eTRE and l TRE resulted in greater reduction in fat mass and visceral fat area by week 8 compared with the control group(P<0.05),with no difference between the intervention groups(P>0.05).Lean mass loss in the eTRE group was greater than that in l TRE group at week 8(P<0.01).4.The 6-h eTRE but not 6-h l TRE alleviated mean glucose,fasting insulin,fasting C-peptide and insulin resistance compared with the control group.5.At week 8,systolic blood pressure was significantly decreased in the 6-h eTRE group(-5.5 mm Hg[95%CI:-8.1,-2.9]),while it was not changed in the 6-h l TRE group(-1.6 mm Hg[95%CI:-4.3,1.0])and control group(0.9mm Hg[95%CI:-1.8,3.7]).No significant differences were observed in diastolic blood pressure and heart rate among the three groups at 4 and 8 weeks(P>0.05).6.Both 6-h eTRE and 6-h l TRE groups produced greater increases in LDL-C than the control group at week 8(P=0.045 and P=0.033,respectively),whereas no difference was observed between the intervention groups(P>0.05).Changes TC,TG,and HDL-C were not significantly different among the three groups at 4 and 8 weeks(P>0.05).Conclusions:These findings shed light on the promise of 6-h eTRE and6-h l TRE as weight loss interventions and suggest that 6-h eTRE may result in better improvements in cardiometabolic health.Part Two Effects of Early and Late Time-Restricted Eating on Metabolic Hormones,Oxidative Stress and Inflammation in Overweight and Obese AdultsObjection:The aim of the study is to evaluate the effects of 6-h eTRE and6-h l TRE on metabolic hormones,oxidative Stress and inflammation,providing scientific evidence for the mechanism of TRE exerts beneficial influence on weight loss and cardiometabolic health.Methods:1.Participants recruitment,sample size estimation and experimental design are described in part one.2.Fasting levels of leptin,adiponectin,high molecular weight adiponectin,IL-6,TNF-α,and 8-isoprostane were measured using ELISA kits on a Spectra Max M2e microplate reader.The SOD activities and MDA concentrations were determined using commercial colorimetric assay kits.The levels of hs-CRP were measured on an AU5800 instrument(Beckman Coulter,Inc.,USA).FT3,FT4,TT3,TT4,TSH,cortisol,and insulin were measured on a DXI800 instrument(Beckman Coulter,Inc.USA).Results:1.The 6-h eTRE and 6-h l TRE groups produced greater reductions of serum leptin by weeks 4 and 8 compared with the control group(P<0.05).Furthermore,there was a significant reduction of serum leptin in the 6-h eTRE group than the 6-h l TRE group at week 4(P<0.05).However,the changes of adiponectin both in total and high-molecular weight did not significantly differ across the three groups at 4 and 8 weeks(P>0.05).The 6-h eTRE group resulted in greater decreases in leptin/adiponectin ratio by week 4 compared with the 6-h l TRE and control groups(P<0.05).2.The 6-h eTRE group induced decreases in TSH and TT3 compared with the 6-h l TRE and control groups(P<0.05),with no significant difference between the 6-h l TRE group and the control group(P>0.05).There were no significant differences in FT3,TT4,and FT4 among the three groups at week 8(P>0.05).3.At week 8,the 6-h eTRE group(3.9 U/m L[95%CI:2.8,4.9])experienced greater increase in SOD than the 6-h l TRE(0.7 U/m L[95%CI:-0.4,1.8])group and control group(0.8 U/m L[95%CI:-0.3,1.9])(P<0.05),and no difference was observed between the 6-h l TRE and control groups(P>0.05).Changes in MDA,8-isoprostane,hs-CRP,TNF-α,IL-6,and cortisol by weeks 4 and 8 were not significantly different among the three groups(P>0.05).Conclusions:The 6-h eTRE may exert beneficial influence on weight loss and cardiometabolic health by reducing the levels of metabolic hormones and increasing antioxidant capacity,while 6-h l TRE may have health benefits by reducing the levels of metabolic hormones.Part Three Mechanism of Early and Late Time-Restricted Eating in Overweight and Obese Adults Based on MetabolomicObjection:The aim of the study is to evaluate the effects of 6-h eTRE and6-h l TRE on serum metabolites,providing scientific evidence for the mechanism of TRE exerts beneficial influence on weight loss and cardiometabolic health from the perspective of metabolomics.Methods:1.Participants recruitment,sample size estimation and experimental design are described in part one.2.Serum metabolites data among the three groups was collected by Liquid Chromatography-Mass Spectrometer.Comparative analysis of serum metabolism among the three groups was using the main component analysis and the orthogonal matrix least squares discriminant analysis.Results:1.There were 179 different metabolites in the serum of the controls,6-h eTRE and 6-h l TRE groups.The metabolites including amino acids,fatty acids,nucleotides,vitamins,and the like.There were 175 different metabolites between the control group and 6-h eTRE group,with 79 different metabolites significantly up-regulated in 6-h eTRE group.A total of 95 different metabolites were screened between the control group and 6-h l TRE group,with 38 different metabolites were significantly up-regulated in the 6-h l TRE group.A total of 79different metabolites were screened between 6-h eTRE and 6-h l TRE,with 42different metabolites were significantly up-regulated in the 6-h eTRE group compared to the 6-h l TRE group.2.The serum differential metabolites of among the controls,6-h eTRE and6-h l TRE groups were mainly enriched in the following pathways:β-alanine metabolism,alanine,aspartate and glutamate metabolism,Valine,leucine and isoleucine biosynthesis,protein digestion and absorption,central carbon metabolism in cancer,aminoacyl-t RNA biosynthesis,cysteine and methionine metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,mineral absorption,ABC transporter family,unsaturated fatty acid synthesis,fatty acid synthesis,degradation and elongation,arachidonic acid metabolism.Conclusions:The 6-h eTRE and 6-h l TRE can cause changes in serum metabolites of overweight and obese adults,which may exert beneficial influence on weight loss and cardiometabolic health by regulating amino acid metabolism and lipid metabolism.