Impact Of Time-restricted Feeding On Mice Immune System And Metabolism In Pediatric Population

OBJECTIVES Early screening and development of effective strategies to prevent and manage obesity and metabolic syndrome are urgently needed to promote health in children and adults.Time-restricted feeding regimen(TRF),ie.,no food consumption for 14-16 hours during the light phase per day,attenuates the fattening traits and metabolic disorders in adults.This study aims to further investigate whether TRF would be protective against similar nutritional challenges in juvenile mice.METHODS We randomly assigned 200 4-week-old wild-type Kunming mice to 3 feeding regimen:TA:TRF during the first 4 weeks(considered to be the childhood phase of mice)before switched to ad libitum(AD)feeding pattern as adults;AA:control group with all subjects stick to AD mode;TT:a group of mice continuously treated with TRF since weaning.Body weight was monitored weekly and blood glucose level was measured at zeigeber time(ZT)13(ZTO:light on)and ZT21.Serum biochemistry examining concentration of insulin,lipids,leptin,ghrelin,and glucagon-like peptide 1 were performed 4&8 weeks after implement of dietary intervention.Sexual maturity was assessed via morphological observation and levels of sex hormones.Flow cytometry analysis and 16S rRNA sequencing were applied respectively to evaluate the immune function and gut microbiota at the end of this experiment.RESULTS After 8 weeks of feeding intervention,the student test showed high levels of body weight and serum glucose in TA mice,compared to AA group(weight:47.1g versus 45.0g,p<0.01;glucose ZT 13:8.38mmol/L versus 7.99mmol/L,p<0.05;glucose ZT 21:9.72mmol/L versus 9.40mmol/L,p<0.05).Meanwhile,TA group demonstrated low concentration of insulin and lipids:insulin:7.199mU/L versus 9.860mU/L,p<0.05;triglyceride 62.92nmol/L versus 83.86nmol/L,p<0.05;total cholesterols:19.95mmol/L versus 20.64mmol/L,p = 0.39;low-density lipoprotein:327.87umol/L versus 401.56umol/L,p<0.05;high-density lipoprotein:253.04umol/L versus 295.21umol/L,p = 0.13.Pathological studies indicated shrunken Langerhans islets,fatty liver disease,as well as rigid,thickening,and proliferation of aortic walls in TA subjects.Sexual development was delayed and proportion of T regulatory cells was dramatically above the control group:6.78%versus 2.69%,p<0.01.CONCLUSIONS Childhood TRF causes pleiotropic adverse effects including severe irreversible metabolic disorders,depressed immune function,and retarded puberty.Microbiota set the stage for TRF to employ downstream reactions on the above changes.These detrimental outcomes and persisting legacy effects are warning signs to public health authorities that guidance of meal quantity and timing for school-aged kids merits consideration.