Methionine Restriction Attenuates Obesity And Inflammation Via Gut Microbiota Remodeling

Obesity induced by high-fat diets is considered to be accompanied with inflammation and oxidative stress.Methionine restriction can reduce body weight without limiting energy intake.It also reduces inflammation and oxidative stress,but the underlying mechanism of benefits remains largely unresolved.High-fat diets could change the structure of gut microbiota.The occurrence of obesity requires the gut microbiota,and the gut microbiota is also closely related to inflammation and oxidative stress.It is still unknown that whether methionine restriction reduce body weight and inflammation and oxidative stress by improving gut microbiota.The purpose of this study was to investigate the effects of methionine restriction on gut microbiota and inflammation and oxidative in high-fat diets mice.Then verified that whether methionine restriction reduce body weight and inflammation and oxidative stress by improving gut microbiota via fecal bacteria transplantation(FMT).Male C57BL/6 mice(4-weeks old,18?20 g)were randomly divided into 3 groups(30 mice in each group):(1)control diet group(C,4%fat,0.86%methionine),(2)high-fat diet group(HM,20%fat,0.86%methionine),(3)high-fat with methionine restriction diet group(LM,20%fat,0.17%methionine),respectively.Ten mice were selected randomly from each group and sacrificed with fasting for 12 hours at the end of twelve weeks.The plasma and gut and gut content samples were taken from the mice after euthanasia.Plasma lipid profiles were measured.Inflammation-related indicators and redox status-related indicators in plasma and gut were tested.The caecal microflora and colon microbiota was analyzed.The gut morphological analysis was performed by microscopy.The remaining mice were continued to be reared until the 30th week.Then divided the HM and LM into 2 groups,respectively.Fecal bacteria transplantation followed by 7-day antibiotic treatment.(1)high-fat diet+ received group C fecal microbiota group(HF-C,20%fat,0.86%methionine),(2)high-fat diet+received group LM fecal microbiota group(HF-MR,20%fat,0.86%methionine),(3)methionine restriction diet+received group C fecal microbiota group(MR-C,20%fat,0.17%methionine),(4)methionine restriction diet+received group HM fecal microbiota group(MR-HF,20%fat,0.17%methionine),respectively.Gavage once every other day for 14 days,then mice were continued to be reared until the 18th day.Mice were sacrificed with fasting for 12 hours.The plasma and gut and gut content samples were taken from the mice after euthanasia.Plasma lipid profiles were measured.Inflammation-related indicators and edox status-related indicators in plasma and gut were tested.The morphological analysis of jejunum and colon was performed by microscopy.The colon microbiota was analyzed.After high-fat diets,the body weight in LM was 5.77 g lower than HM.Compared to group HM,LM significantly decreased the levels of triglyceride(TG)and cholesterol(TC)and low density lipoprotein cholesterin(LDL-C)in plasma,the levels of malonaldehyde(MDA)in plasma and colon,the levels of lipopolysaccharide(LPS)and LPS-binding protein(LBP)in plasma,the relative expression of proinflammatory-related mRNA in ileum.LM significantly increased the levels of high density lipoprotein cholesterin(HDL-C)in plasma,the levels of total antioxidant capacity(T-AOC)and glutathione peroxidase(GSH-Px)and glutathione/oxidized glutathione(GSH/GSSG)in plasma,the levels of T-AOC and GSH/GSSG in ileum,the levels of GSH/GSSG in colon.LM significantly increased the diversity and evenness index of caecal microflora and colon microbiota,the relative abundance of Allobaculurn and Bifidobacterium and Oscillospira of colon microbiota.LM significantly decreased the relative abundance of Akkermansia.After FMT,the body weight in HF-MR was 3.53 g lower than HF-C,the body weight in MR-HF was 4.16 g lower than MR-C.Compared to HF-C,HF-MR significantly decreased the levels of TG and TC in plasma,the levels of MDA in plasma,the levels of LPS and TNF-? and IL-1? and IL-8 in plasma.HF-MR significantly increased the levels of T-AOC and GSH-Px and CAT in plasma,the relative abundance of Bifidobacterium of colon microbiota.Compared to MR-C,MR-HF significantly decreased the levels of T-AOC and CAT in ileum,the levels of T-AOC in colon.MR-HF significantly increased the levels of TNF-a and IL-8 in plasma.The high-fat diets decreased the diversity of gut microbiota,destroyed the structure of gut microbiota(decreased the relative abundance of Bifidobacterium),led to the occurrence of obesity,accompanied by inflammation and oxidative stress.Methionine restriction decreased weight gain by increasing the diversity of gut microbiota and improving the structure of gut microbiota(increased the relative abundance of Bifidobacterium),and attenuating inflammation and inhibiting oxidative stress.