Correlation Of Lipid Metabolism And Inflammation With Gut Microbiota In High-fat/high-sugar Diet Induced Obese Mice By Smilax China L.polyphenols

Obesity has become a global health issue and is a major risk factor for type 2 diabetic,fatty liver disease and cancer.Currently,long-term use of synthetic drugs treating obesity have side effects.Using natural products,dietary intervention is a form of a health and safety.Recently,Obesity has been shown to be closely linked to gut microbiota,and dietary factors is the key to the change of microbiota.Therefore,gut microbiota as targets by dietary intervention to prevent obesity is a promising way.Smilax china L.is also used as traditional herbal medicine in China.It contains multifarious naturally bioactive components,such as flavonoids,polyphenols,and their extracts possessed a variety of biological effects.such as antibacterial,anti-inflammatory etc.But the active ingredient of Smilax China L.by regulating gut microbiota play the role of lipid-lowering diet mechanism has not been reported.This study polyphenols extracted from Smilax China L.to explore its effect on gut microbiota and obesity and inflammation has important significance.Our previous studies showed that Smilax China L.ethanol extract(SCE)and Smilax China L.flavonoids(SCF)were effective in preventing obesity caused by high fat diet.However,it is not clear whether Smilax China L.polyphenols(SCLP)can play a lipid-lowering role.The investigated mechanism of Smilax China L.polyphenols in preventing obesity from the perspective of gut microbiota.In this study,C57BL/6J mice fed with high-fat/high-sugar(HFHS)diet were used as animal models.First,the relationship between the lipid-lowering effect of SCLP and gut microbiota.Second,the effects and correlations of SCF on lipid metabolism pathway,gut microbiota and and its metabolites-short-chain fatty acids(SCFAs)were preliminarily studied,in order to further enrich the lipid-lowering mechanism of SCF.Again,whether SCF can improve HFHS-induced the chronic inflammation by regulating gut microbiota.1.Three phenolic acids and three flavonoids in SCLP were identified by liquid chromatography-mass spectrometry.The total phenolic content of SCLP was determined by Folin-phenol method to 91.8%.Subsequently,mice were fed a normal diet,HFHS feeding with or without SCLP or Orlistat by gastage for 12 weeks,and the effects of SCLP on weight changes,serum indexes and gut microbiota in HFHS-induced obese mice were determined.The results showed that SCLP reduced body weight gain,fat deposition,and lipid content in serum and liver,and effectively improved abnormal glucose tolerance.The16 S r DNA results showed that SCLP decreased the ratio of Firmicutes/Bacteroidetes,the relative abundance of Erysipelotrichaceae,Lachnospiraceae,Desulfovibrionaceae and Streptococcaceae,and increased the relative abundance of Akkermansiaceae in the gut with lipid-lowering effect.These results suggest that SCLP can prevent HFHS-induced obesity in mice by regulating the composition of gut microbiota.2.After SCF intervention,body weight,serum parameters,blood glucose,liver lipids and related to expression levels of gene and protein were determined.Changes in gut microbiota and SCFAs of mice were detected by 16 S r DNA sequencing combined with targeted metabolomics.To explore the effects of SCF on gut microbiota composition,SCFAs production and lipid metabolism.The results showed that SCF reduced body weight gain,fat accumulation,serum lipid parameters,hepatic steatosis and improved glucose homeostasis.SCF increased adiponectin,adiponectin-receptor(Adipo R1/R2)was increased.At the same time,SCF up-regulated the expression of AMPKα,PPARα CPT-1α,UCP-1,which is related to fatty acid β-oxidation,and down-regulated the SREBP1-c,FAS,ACC,which is related to adipogenesis.In addition,SCF reduces energy absorption,and plays the role of lipid lowering by increasing Akkermansia,which has lipid-lowering effect in gut,and reducing the Bifidobacterium,g＿Eubacterium＿xylanophilum＿group,Lachnospiraceae,and other fermentation produced SCFAs levels,thereby reducing lipid-lowering and weight loss.Spearman correlation analysis showed that obesity phenotype,SCFAs levels,and gut microbiota changes were significantly correlated.3.SCF decreased serum LPS,TNF-α and IL-6 levels,increased the release of adiponectin and IL-10,up-regulated the m RNA expression of IL-10,AMPK and PPARγ in adipose tissue,and down-regulated TNF-α in the liver.The m RNA expression of IL-6 and protein expression of Toll-like receptor 4(TLR4),nuclear factor-κB(NF-κB),phosphorylated IκB-α and p65.In addition,SCF significantly increased the relative abundance of intestinal barrier protective bacteria Akkermansia,and decreased the abundance of pro-inflammatory bacteria such as Streptococcus,Facecalibaculum,and endotoxin-producing bacteria-Desulfuribrio,thereby reducing HFHS-induced inflammation.Spearman correlation analysis showed that there was a significant correlation between inflammatory parameters and changes of gut microbiota.To sum up,this study result shows that SCLP dosing effectively prevent obesity in HFHS-induced mice,and improve the imbalance of gut microbiota.In addition,SCF improve lipid metabolism disorders may be through the following ways: on the one hand,SCF enhancing adiponectin-receptor/AMPK pathway inhibition of lipid synthesis,increasing fatty acid oxidation,and ultimately achieving the lipid-lowering and weight loss effect.On the other hand,SCF reduced the energy absorption of SCFA-producing bacteria and achieved the effect of lipid lowering and weight loss in mice.At the same time,SCF decreased the serum LPS level and inhibited the activation of TLR4/NF-кB signaling pathway by decreasing the pro-inflammatory bacteria and increasing the anti-inflammatory bacteria,thus alleviating HFHS-induced inflammation in mice.These results provide a theoretical basis for preventing obesity and metabolic syndrome from Smilax China L.