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The Effect And Mechanisms Of Artemisia Sphaerocephala Krasch Polysaccharide And Its Acetylated Derivates In Preventing Obesity

Posted on:2021-12-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:J J LiFull Text:PDF
GTID:1524307316496524Subject:Biomedical engineering
Abstract/Summary:PDF Full Text Request
As a type of metabolic syndrome,obesity is commonly associated with dyslipidemia,and systematic inflammation and is believed to increase the morbidity of cardiovascular disease,type 2 diabetes,and even cancers.Accumulating evidence demonstrates that imbalanced gut microbiota contributes to the energy harvest of host and subsequently promote the development of obesity.Modulation of gut microbiota has been proved as an efficient way to prevent the high-fat-diet(HFD)induced obesity and its related complications.Our previous study indicated that Artemisia sphaerocephala Krasch polysaccharide(ASKP)could efficiently protect db/db diabetic mice from hyperglycemia and dyslipidemia.The anti-obesity activity and the attenuation on gut dysbiosis capability of ASKP have not been reported.In the current study,we evaluated the effects of ASKP and its two fractions on diet-induced obesity in mice and analyzed the potential mechanisms with respect to hepatic lipid metabolism,intestinal barrier function and inflammatory response,production of short-chain fatty acids(SCFAs)and modulation of gut microbiota.Besides,the potential improvement on the anti-obesity activity of ASKP and its two fractions induced by acetylation were also evaluated.The obtained results are as follows:(1)The anti-obesity effects exerted by ASKP.Middle dose(400 mg/kg/day)and high dose(800 mg/kg/day)of ASKP could effectively alleviate high fat diet(HFD)-induced obesity in mice.The final body weight,body weight gain,liver weight,epididymal fat weight and energy efficiency were dramatically decreased and the dyslipidemia and metabolic endotoxaemia were also ameliorated.Analysis on gut microbiota revealed that Odoribacter,AF12,Helicobacter and Mucispirillum were positively correlated with the development of obesity while the others,such as Dorea and Roseburia,showed their positive role in preventing obesity.(2)The capability of the major fractions of ASKP in preventing obesity and potential mechanisms.It was revealed that ASKP,60P and 60S showed similar effects on preventing HFD-induced obesity and 60P was more efficient than ASKP and 60S.The related mechanisms included:(1)preventing the excessive lipid accumulation in liver with the dramatically suppressed genes related to lipid metabolism(SREBP-1c、PPARγ、FAS and ACC-1);(2)attenuating the intestinal mucosal barrier dysfunction with the suppression on colonic genes of inflammatory response(TNF-α、IL-1βand IL-6)and the up-regulation on tight junction proteins-ZO-1 and occludin.(3)modulation of gut microbiota with dramatic enrichment of beneficial genera that negative related to obesity(Bifidobacterium,Allobaculum and Olsenella)and suppression of harmful ones that positive related to obesity(Mucispirillum and Helicobacter).Co-occurrence network of different genera revealed that the enriched Bifidobacterium,Allobaculum and Olsenella showed no significant interaction with each other but were negative to the suppressed Mucispirillum and Helicobacter.(4)dramatically increasing the production of SCFAs including the increased fecal concentration of acetate,propionate,butyrate and total SCFA and the decreased ratio of acetate to propionate.(5)suppressing microbial metabolic pathways related to obesity and gut dysbiosis,such as valine,leucine,and isoleucine biosynthesis,and nitrogen metabolism.(3)Effects of acetylation on the physicochemical properties of ASKP and its two fractions and their stability during gastrointestinal digestion.Acetylated derivates of ASKP,60P and 60S were obtained with the acetylation under alkaline conditions and the results were further confirmed with FTIR and ~1H NMR.Analysis on molecular characteristics indicated that there were no dramatic changes on the molecular weight of 60P,60S and the two fractions in ASKP after acetylation but the ratio of 60S-related fraction in ASKP was dramatic decreased.The contents of galactose and arabinose in ASKP increased but those of glucose and xylose decreased.There were no dramatic changes on the monosaccharide composition of 60P and 60S before and after acetylation.Besides,acetylation increased the apparent viscosity of acetylated ASKP-ASKPA but decreased that of acetylated 60P-60PA.Simulated gastrointestinal digestion revealed that ASKP,60P and 60S could transit through gastrointestinal tract without dramatic degradation before and after acetylation.(4)Prediction of the effects of acetylated ASKP(ASKPA)and its two fractions(60PA and 60SA)in modulating gut microbiota and SCFA production via in vitro fermentation by human fecal microbiota.Results revealed that both the native polysaccharides and their acetylated derivates could be utilized by gut microbiota at a relative low rate and acetylation improved the utilization rate of ASKPA and 60PA.All the three native polysaccharides could promote the promote the production of acetate and total SCFA.Both ASKP and 60S showed the stronger capability to increase the production of propionate than 60P.Acetylation improved the capability of ASKPA and60PA in promoting the propionate production.Analysis on gut microbiota revealed that there was no dramatic changes on the dominant genera in the groups added with the native and acetylated polysaccharides.Bacteroides could be the major genus in utilizing ASKP,60P and their acetylated derivates.Meanwhile,Bacteroides,Parabacteroides and Collinsella may play the important roles in utilizing 60S and its derivates.Besides,metabolic pathways of microbiota were dramatically changed by acetylation and down-regulation of propanoate metabolism was the potential pathway to increase the concentration of propanoate in fermentation liquids.Above all,acetylated modification might be an effective way to improve the anti-obesity activity of ASKP and its two fractions.(5)The capability of acetylated derivates of ASKP,60P and 60S(ASKPA,60PA,and 60SA)in preventing obesity and potential mechanisms.It was revealed that ASKPA,60PA and 60SA showed similar effects on preventing HFD-induced obesity and ASKPA and 60PA were more efficient than ASKP.The related mechanisms included:(1)stronger capability in preventing the excessive lipid accumulation in liver with the dramatically suppressed genes related to lipid metabolism(SREBP-1c、PPARγ、FAS and ACC-1);(2)maintaining the capability in attenuating the intestinal mucosal barrier dysfunction with the suppression on colonic genes of inflammatory response(TNF-α、IL-1βand IL-6)and the up-regulation on tight junction proteins-ZO-1 and occludin.(3)modulation of gut microbiota with dramatic enrichment of beneficial genera that negative related to obesity(Akkermansia)and suppression of harmful ones that positive related to obesity(Bilophila、Desulfovibrio、Pseudomonas and Streptococcus).Co-occurrence network of different genera revealed that the beneficial genera Akkermansia,Bifidobacterium,and Allobaculum showed no significant interaction with each other but were negative to the suppressed Odoribacter and Bilophila.(4)stronger capability in promoting the production of SCFAs with the increased concentrations of acetate,propionate and butyrate.(5)modulation on microbial metabolic pathways related to SCFA production.The suppressed propanoate metabolism may contribute to the increased propionate concentration in mice administrated with acetylated polysaccharides.Compared with the current reports,this paper has the following novelty:revealing the role and mechanisms of Artemisia sphaerocephala Krasch polysaccharide and its two fraction with different molecular weight in the intervention of obesity development in mice;developing the method to improve their effects via acetylation modification;revealing the role of gut microbiota and the SCFA production in modulating metabolisms for these polysaccharides and their acetylated derivatives.
Keywords/Search Tags:Artemisia sphaerocephala Krasch polysaccharide, Anti-obesity activity, Gut microbiota, Acetylation, Akkermansia
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