The Efficacy And Mechanism Of Resistant Starch For Obesity

Resistant starch(RS),also known as fermented fiber,has the characteristics of soluble and insoluble dietary fiber.RS is not easily hydrolyzed by amylase in the small intestine,but can be fermented by gut microbiota and produce short-chain fatty acids in colon.Studies have shown that RS can reduce body fat in obese rodents.However,its effect has not been found in human subjects.In this study,the effects of RS on body weight,fat mass,glucose metabolism and other metabolic phenotypes of normal weight and overweight obese people were studied by randomized crossover experiments.The effects of RS intervention on human intestinal hormones,gut microbiota and metabolites were also studied,and its mechanism was further explored through animal experiments1.Resistant Starch Intervention in Normal Weight Subjects:a randomized crossover trialOBJECTIVE:RS has been reported to reduce body fat in obese mice.However,this effect has not been demonstrated in human.It is reported that high fat diet and tea polyphenols can affect RS fermentation in the intestine,suggesting that dietary components may affect the role of RS.Therefore,dietary components should be strictly controlled in RS clinical study.In this study,we provided subjects with a balanced and isocaloric diet three meals a day according to the dietary guidelines for Chinese residents,and the effect of 40 g/day RS on body fat of normal weight subjects was testedRESEARCH DESIGN AND METHODS:A randomized,double-blind,crossover-design clinical trial was conducted to observe the effects of 40 g/d RS and iso-energy controlled starch(CS)on body fat,intestinal hormones,gut microbiota and metabolites in 19 normal weight subjects.Anthropometric parameters and body fat composition were measured.VFA and SFA were measured by magnetic resonance imaging(MRI).Biochemical parameters were measured.Glucose tolerance and insulin sensitivity were assessed by standard meal tolerance test and hyperinsulinemic-euglycemic clamp.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum GLP-1 and PYY level,16S RNA pyrophosphate sequencing was used to study the composition of gut microbiota,and the level of small molecule metabolites in blood and urine was detected by liquid chromatography mass spectrometry.SCFAs were detected by gas chromatography.RESULTS:After 4 weeks 40 g/day RS intervention,VFA and SFA of normal weight subjects decreased significantly,insulin and GLP-1 secretion increased significantly 30 minutes after meal,urea nitrogen level decreased significantly,but there was no significant change after CS intervention.16S rRNA sequencing results showed that at genera level,15 genera of bacteria decreased significantly after RS intervention,while the abundance of Ruminococcaceae_UCG-005 increased.In addition,the abundance of baseline Streptococcus,Ruminococcus torques group,Eubacterium hallii group and Eubacterium eligens group was significantly correlated with the increase of insulin and GLP-1 secretion after RS intervention and the decrease of VFA and SFA.CONCLUSION 40 g/d RS intervention can effectively reduce VFA and SFA,increase insulin and GLP-1 secretion,and change the composition of gut microbiota in normal weight subjects.2.Resistant Starch Intervention in Overweight and Obesity Subjects:a randomized crossover trialOBJECTIVE:The first part of the study found that 40 g/d RS intervention could reduce abdominal fat and change the composition of gut microbiota in normal weight subjects.However,it is not clear whether RS can be used as a functional food component to treat obesity,and how changes in gut microbiota caused by RS intervention.Therefore,a randomized crossover study is urgently needed to link the effects of RS on gut microbiota in obese individuals with changes in host metabolic phenotypes.this part of the study provided subjects with a balanced and isocaloric diet According to the AHA/ACC/TOS guidelines for the management of overweight and obesity in adults,and the effects of RS and CS on the body weight of overweight and obese subjects for 8 weeks was tested.RESEARCH DESIGN AND METHODS:A randomized,double-blind,crossover-design clinical trial was conducted to observe the effects of RS and CS on body weight,body fat,gut microbiota and metabolites of 37 overweight and obese subjects on a uniform diet for 8 weeks.The anthropometric parameters,body fat composition,VFA and SFA were measured by MRI,and biochemical indexes were determined.The subjects’ glucose tolerance and insulin sensitivity were assessed by standard meal tolerance test and hyperinsulinemic-euglycemic clamp.Serum adipocyte fatty acid binding protein(A-FABP),adiponectin and angiopoietin-like protein 4(ANGPTL4)were detected by ELISA and analyzed by liquid chromatography-mass spectrometry.The levels of small molecule metabolites in blood and urine were detected,and the composition of gut microbiota was studied by Metagenomic analyses.RESULTS:40 g/d RS consumption for 8 weeks could significantly reduce the body weight,VFA and SFA of overweight and obese subjects,and significantly improve insulin sensitivity,while CS consumption did not show the above changes.RS consumption could significantly change the composition of gut microbiota.Four species,including Bifidobacterizun adolescentis,Bifidobacterizum longzum,Dorea longicatena and Ruminococcus bromiii,increased significantly after RS consumption.Eight species after RS intervention,including Alisipes putredinis,Bacteroides coprophilus,Bacteroides ovatus,Bacteroides vulgatus,Eubacterium eligens,Odoribacter splanchnicus,Parbacteroides merdae and Prevotella copriwere significantly reduced.Among the 12 species,B.adolescentis and P.Copri were most closely related to phenotype,and were significantly related to changes in body weight,fat mass and insulin sensitivity.B.adolescentis may play a key role in obesity,as its increase is significantly correlated with the decrease of BMI,waist circumference and VFA.It was also found that the increase of B.adolescentis abundance after RS intervention was significantly correlated with the levels of serum carnitine,energy metabolism and lipid-related metabolites of host metabolites.At the same time,serum propionate concentration increased significantly after RS intervention,while other serum short chain fatty acids(SCFA),including acetate and butyrate,showed no significant difference.CONCLUSION:8 weeks 40 g/day RS intervention can reduce body weight and improve insulin sensitivity in overweight and obese subjects.RS intervention can remodel gut microbiota of overweight and obese subjects,and cause changes in specific bacteria species The changes of host metabolic phenotype after RS intervention are closely related to changes of intestinal flora and metabolites of host.3.Mechanisms of Resistant Starch on ObesityOBJECTIVE:Previous results showed that RS could reduce the body weight and body fat of overweight and obese subjects,change the composition of gut microbiota and increase the level of propionate.However,the mechanism of RS intervention on obesity remains unclear.Therefore,this part further explores the direct effect of RS-mediated changes in intestinal flora and propionic acid on obesity intervention and its possible mechanism through animal experiments.RESEARCH DESIGN AND METHODS:After the intervention of RS and CS,the feces of the subjects were transplanted into sterilized mice(human-mouse feces transplantation).The direct effect of RS-mediated intestinal flora on obesity was studied The intestinal permeability,the expression of intestinal tight junction protein,the level of endotoxin(LPS)and the expression of inflammatory factors were further studied.The circulating ANGPTL4,intestinal lipase activity and intestine were detected.To study the mechanism of intestinal flora mediated by resistant starch to improve obesity by fat content in cavity and feces.Diet-induced obesity(DIO)mice were treated with sodium propionate by gavage.The energy metabolism of DIO mice was measured by CLAMS to study the regulatory effect of propionic acid on obesity.RESULTS:After 2 weeks of human-mouse feces transplantation,compared with mice receiving CS intervention,mice receiving RS intervention had significantly lower body weight,body fat and improved glucose tolerance.After RS intervention,the levels of inflammatory factors and the expression of inflammatory factors in intestinal tract of mice with gut microbiota were significantly lower than those of mice with gut microbiota after CS intervention,and the levels of LPS in mesenteric adipose tissue and circulation were significantly lower than those of mice with intestinal flora after CS intervention.After RS intervention,the expression of intestinal tight junction protein ZO-1 and occludin increased significantly and intestinal permeability also decreased significantly in mice with gut microbiota.At the same time,compared with the mice receiving CS intervention,the expression of ANGPTL4 in ileum,the activity of intestinal lipase,the content of triglyceride(TG)in ileum and the content of TG in feces of the mice receiving RS intervention were significantly increased.In addition,compared with the control group,propionic acid intervention in DIO mice for 4 weeks could significantly reduce body weight,body fat,improve glucose tolerance and insulin sensitivity,increase oxygen consumption,but no significant changes in food intake and activity.CONCLUSION:RS-mediated gut microbiota has a direct effect on obesity.The gut microbiota reshaped by RS intervention can reduce metabolic endotoxemia and chronic inflammation by decreasing intestinal permeability.At the same time,the gut microbiota altered by RS intervention increase the expression of ANGPTL4 in small intestine and reduce intestinal lipid absorption.In addition,increased propionate by RS intervention can reduce obesity by increasing energy consumption.Gut microbiota and SCFA mediate the effect of RS on obesity.