Effects Of κ-Carrageenan On High-fat-diet Induced Obesity And Intestinal Homeostasis In Mice

Obesity is a chronic metabolic disease,the imbalance of metabolism and energy expenditure is the root cause of obesity.The gut is the center of metabolism regulation,and metabolic disorders may begin in the gut,previous studies had shown that the natural dietary factors in food can regulate the the intestinal microecosystem’s balance to improve obesity through diet intervention.κ-carrageenan(κ-CGN)is a kind of undigested macromolecular polysaccharide,which has the basic characteristics of soluble dietary fiber and may have the potential to regulate intestinal homeostasis.Thus,different doses of κ-carrageenan were used to intervene the high-fat-diet induced obesity in mice.The changes of body weight,body fat rate,blood glucose,blood lipid,inflammation level,gut microbiota and its metabolite SCFAs in the obese mice fed with high-fat diet were analyzed,and the effect and its mechanism of κ-carrageenan on the mice fed with high-fat diet were discussed.It will provide a theoretical basis for the study of κ-carrageenan in diet.8-week-old mice were randomly divided into four groups: normal control group(ND);high fat control group(HFD);low dose carrageenan group(LCGN): 0.2% w/wκ-CGN;high dose carrageenan group(HCGN): 1% w/w κ-CGN.The intervention time was 8 weeks.The weight and food intake of rats were recorded every week.At the 16 th week,the obesity related phenotypes of mice were detected: FBG,OGTT,blood lipid,organ mass,pathological sections of liver and adipose tissue;the levels of serum insulin,LPS,IL-6,TNF-α were detected by enzyme linked immunosorbent assay(ELISA).The intestinal microenvironment and its metabolite SCFAs were detected: AB-PAS and H&E staining of small intestine and colon,Quantitative Real-time PCR(qRT-PCR)and Western Blot(WB)were used to detect the mRNA and protein expression level of ZO-1and Occludin in colon;The contents of mouse colon were sequenced and bioinformatics analyzed based on Illumina miseq high-throughput sequencing platform,and content of SCFAs was analyzed based on GC-MS target metabonomics.The body weight,body fat rate,blood lipid,and fasting blood glucose were significantly reduced(P<0.05)in both LCGN and HCGN groups.Besides,the area under blood glucose curve(AUC)was decreased significantly in LCGN group(P<0.01),while no significant difference was observed in HCGN group.The serum TNF-α content in LCGN group was significantly lower than that in HFD group(P<0.05),but the TNF-αcontent in HCGN group was not significantly different with the HFD group.LCGN and HCGN decreased the content of LPS in serum(P<0.05),increased the secretion of intestinal mucus,the depth of crypt and the expression of intestinal tight junction protein ZO-1 and Occludin,which improved the intestinal barrier function of obese mice.Sequence analysis of gut microbiota showed that LCGN and HCGN changed the composition of gut microbiota,decreased the ratio of Firmicutes to Bacteroides,decreased the relative abundance of Proteobacteria and Deferribacteres,increased the relative abundance of Verrucomicrobia,and LCGN was more similar to ND group.Compared with HFD group,LCGN and HCGN can promote the relative abundance of SCFAs producing bacteria such as Akkermansia,Faecalibaculum,Roseburia and Bifidobacterium,which increased the content of SCFAs.κ-Carrageenan could regulate the gut microbiota structure of obese mice,increase the content of short chain fatty acids,and then inhibit the excessive weight growth,fat accumulation,blood lipid and glucose disorders,improve systematic inflammation and intestinal barrier to prevent obesity.