Time-restricted Feeding Alleviates The Harm Of High-fat Diet Feeding

Background:As the regular daily meals of a lot of people are containing more and more carbohydrate and fat,metabolic syndrome has become a major health burden for people around the world.Metabolic syndrome is a group of clinical syndromes manifested as obesity,hyperglycemia,hypertension,high triglycerides and low high-density lipoprotein cholesterol.It is an important risk factor for cardiovascular disease and all-cause death.Therefore,healthy diet has triggered a wide range of discussions.Previous studies have shown that time-restricted feeding,as a new regimen of eating,can lead to certain health effects including delaying aging,reducing weight,and improving metabolic disorders caused by high-fat diets via reducing the daily energy intake.Along with deepening of research,time-restricted feeding has been considered as an effective intervention for metabolic syndrome,but its physiological mechanism remains to be discussed.This study aims to implement a time-restricted feeding on obese mice fed a high-fat diet to verify its relieving effect and explore the physiological mechanism.Methods:Three groups of a total of sixty 8-week-old male Kunming mice received a normal diet,a high-fat diet,or a time-restricted high-fat diet respectively.The experimental period lasted for 8 weeks.Mice were weighed and the calorie intake were measured and recorded weekly.Hepatic pathological slides and serum metabolites were obtained and tested after the experimental period ended.Gut microbiota,lipid metabolites and the hepatic cellular levels of Per1,Cry1,Bmal1,SIRT1,SREBP and PPARa were examined at four different timepoints.The cellular expression levels of hepatic genes and the composition of gut microbiota were compared between different timepoints,namely zeitgeber time 0,zeitgeber time 8,zeitgeber time 12 and zeitgeber time 20.Results:Mice that received a non-restricted high-fat diet suffered from more weight gain and greater liver steatosis compared to mice received a non-restricted normal diet.Mice in the group of time-restricted high-fat diet gained less body mass,developed milder liver steatosis,and had hepatic levels of triglycerides,higher Bacteroidetes abundance and lower Firmicutes abundance than mice in the group of non-restricted high-fat diet(p<0.05).Mice in the group of time-restricted high-fat diet showed weak circadian rhythms of hepatic expression of Per1,Cry1 and Bmal1,which was same with mice in the group of non-restricted high-fat diet,while totally different from those of mice fed a normal diet ad libitum.Mice in the group of time-restricted high-fat diet showed different circadian rhythmic patterns of hepatic protein levels of SIRT1,SREBP and PPARa compared with mice in the group of non-restricted high-fat diet or mice in the group of normal diet,as well as the circadian rhythms of the composition of microbiota.Conclusions:We have successfully constructed an obese mouse model using high fat diet,and also successfully implemented time-restricted feeding on the obese mice.Time-restricted feeding is able to relieve the harm of high-fat diet feeding and is associated with healthier metabolic status,probably due to changes in the circadian rhythm of molecules related to hepatic lipid metabolism and gut microbiota.