The Regulatory Mechanism Of Capsaicin To Abnormal Lipid Metabolism In High-Fat Diet Rats

In recent years,due to the influence of western dietary habits,China’s dietary structure has gradually changed from the traditional high-carbohydrate and high-fiber diet to the high-fat and high-sugar diet,which has led to the long-term elevation of blood lipid levels in many people,resulting in diseases like inflammation and atherosclerosis.Therefore,regulating abnormal lipid metabolism which is brought by high fat diet becomes an important measure to avoid this kind of disease happening and getting worse.As a spicy and pungent food which is widely consumed,capsaicin has been proofed that it can adjust abnormal lipid metabolism in recent years’ reports.Presumably,the possible mechanisms are as follows: The first is capsaicin stimulates vanilloid receptor 1(TRPV1)to activate genes related to lipid metabolism in body tissues;The sceond is capsaicin can change the composition and metabolites of intestinal flora,especially increase the abundance of Akkermansia and increase the content of short-chain fatty acids to improve lipid metabolism.However,further studies are required to confirm these findings.Hence,we use association of multiple omics to analyze regulatory mechanism of capsaicin to homeostasis of intestinal flora at the intestinal level and further analyze metabolism mechanism of capsaicin at the molecular level.The main results are as follows:(1)Capsaicin can effectively reduce plasma Triglycerides(TG)and Total cholesterol(TC)concentrations by change intestinal bile acid composition in high-fat diet SpragueDawley(SD)rats.The present study used LC-MS to explore the influence of capsaicin to bile acid composition of SD rats which were fed by high fat diet and found that capsaicin could adjust Farnesoid X receptor(FXR)to restrain the expression of Fibroblast growth factor 15(Fgf15)and promote the expression of Cholesterol 7α –hydroxylase(CYP7A1)and finally decreased Triglycerides(TG)and Total cholesterol(TC)by increasing the levels of β-Muricholic acid(β-MCA),Chenodeoxycholic acid(CDCA),Deoxycholic acid(DCA)and Tauro-β-muricholic acid Sodium Salt(T-β-MCA),which helped the body inhibit the accumulation of fat.(2)This study utilized 16 S rRNA sequencing to detect gut microbiota in cecal contents and found that capsaicin decreased the abundance of Firmicutes and promoted the presence of specific fermentative bacteria populations,such as Bacteroidales＿S24-7,Akkermansia et al.;Meanwhile,optimal dose(0.01%)could increase the abundance of Desulfovibrio.These microbial structural changes promote the accumulation of shortchain fatty acids(SCFAs),candesartan,and arginine et al.,thus regulating the abnormal lipid metabolism brought on by a high-fat diet.(3)To confirm the relationship between capsaicin lipid lowering mechanism and intestinal Akkermansia bacteria,TRPV1 germ-free mice,which were selectively ablated with resin-toxin,were adopted as the experimental model to be fed with capsaicin and transplanted with Akkermansia,and found that both the transplantation of Akkermansia and the feeding of capsaicin can reduce the level of blood lipid in germ-free mice with high fat diet,and the effect will be better when Akkermansia was combined with capsaicin.Capsaicin can increase the thickness of colonic mucus layer through TRPV1 ion channels and promote the expression of Mucin2(Muc2)and Mucin3(Muc3)genes,thereby increasing Muc2 mucin secretion and providing sufficient carbon and nitrogen sources for Akkermansia.This may be one of the reasons why capsaicin increased the abundance of Akkermansia in the intestinal tract of rats fed a high-fat diet.(4)To probe the role of TRPV1 in the lipid-lowering effect of capsaicin.We used resintoxin(RTX)to ablate the TRPV1 channel in sterile mice and found that capsaicin could improve dyslipidiosis caused by high fat diet even in the absence of TRPV1 ion channel and intestinal flora.It decreased the concentration of Low-density lipoprotein(LDL-C)and TG,increased the concentration of High-density lipoprotein(HDL-C),and decreased the plasma endotoxin(LPS)and pro-inflammatory factors Interleukin(IL)-6.Capsaicin could affect the classical and alternative pathways of cholesterol conversion by changing the composition of bile acids,reducing the concentration of Sodium Glycocholate Hydrate(GCA),Ursodeoxycholic acid(UDCA)and Glycochenodeoxycholic acid Sodium Salt(GCDCA).First,the change of bile acid composition affects the expression of colon FXR,inhibits the expression of colon Fgf15,promotes the expression of liver CYP7A1,and thus reduces TC and TG.The second is to inhibit and change the composition of bile acids and inhibit the expression of Oxysterol7α-hydroxylase(CYP7B1)gene in colon and CYP7B1 protein in liver,thus inhibiting fat accumulation.(5)Capsaicin and dietary fiber are natural active ingredients and have positive effects on obesity and metabolic diseases respectively.TC and LDL-C were effectively decreased,the β-diversity of gut microbes were increased,the abundance of beneficial strains such as Allobaculum and Akkermansia increased and Desulfovibrio abundance in a 0.01% dose of capsaicin also reduced when capsaicin and dietary fiber were combined together.In addition,the combination of capsaicin and dietary fiber significantly increased the level of SCFAs in cecal feces of rats,and promoted the accumulation of arginine and other metabolites.