| According to statistics from the World Health Organization(WHO),39% of adults worldwide are overweight and 13% are obese.Obesity is a metabolic disease,mainly caused by the insufficient utilization of fatty acids due to the long-term imbalance of energy intake and expenditure,resulting in.Obesity contributes to disorders of host and intestinal flora metabolism,leading to the occurrence of a variety of serious diseases such as type 2 diabetes,cardiovascular disease,non-alcoholic fatty liver,coronary heart disease.Exercise intervention is not enough effective due to the need to change people’s lifestyle,while surgery and medication caused adverse side effects.Therefore,it is necessary and urgent to find and develop new safe and effective strategies to prevent and treat obesity.In recent years,regulating the intestinal flora to interfere with obesity has proven to be a safe and effective strategy.How the intestinal flora affects the host has also received increasing attention.At present,it has been widely recognized that the intestinal flora metabolites are the key substances for the intestinal flora to affect the host.However,how do external factors such as food and active substances affect the intestinal flora and its metabolism,and how the intestinal flora metabolites affect the metabolism of the host? The mechanism of the two processes is not clear yet.Therefore,research on the improvement of obesity by active substances mediated by intestinal flora and its metabolites will help to discover new valuable active substances and promote their applications.Inonotus obliquus is an edible and medicinal mushroom that has been used as a medicine in China,Russia and other places for hundreds of years.It has many biological activities,including hypoglycemic,hypolipidemic,antitumor,antioxidant,antiinflammatory properties.In recent years,there have been many reports on the active ingredients of Inonotus obliquus and their related physiological functions,but there are few studies on the regulation of obesity by Inonotus obliquus extracts.The effect and mechanism of Inonotus obliquus extracts are not yet clear,on the metabolism of obese individuals and the metabolism of intestinal flora.In order to explore the effect and mechanism of Inonotus obliquus extracts in improving obesity,we extracted Inonotus obliquus polysaccharide(IOE)rich in β-polysaccharide and Inonotus obliquus ethanol extract(IOE)rich in triterpenes and polyphenols.Then,we conducted the following exploration.(1)Explore the effect of IOP on flora metabolism and host metabolismFirst,we used IOP to intervene in high-fat diet-fed mice(HFD-fed mice),and used metabolomics techniques to determine the metabolites in urine and feces.Results showed that IOP supplementation improved the body weight gain(BWG),energy efficiency,and glucose and lipid metabolism of HFD-fed mice.In host metabolism,IOP up-regulated the level of tricarboxylic acid cycle(TCA cycle)and the level of nutrient degradation in HFD-fed mice.In flora metabolism,IOP increased the intestinal butyrate level of HFD-fed mice.Through spearman correlation analysis,we found a significant correlation between butyrate and citrate.It was confirmed that the SCFA synthesis metabolism of the intestinal flora is closely related to the host TCA cycle.IOP increased the host’s TCA cycle level and inhibits BWG by increasing intestinal butyrate.(2)Study on the mechanism of IOE and IOP improving the metabolism of HFDfed mice.In order to explore the mechanism of how two Inonotus obliquus extracts improve the metabolism of obese mice,we used IOE and IOP to intervene in HFD-fed mice.In addition to determining the metabolites in urine and feces,we also detected the expression of genes related to glucose and lipid metabolism in the liver,the metabolite composition of serum and cecal contents,and the sequence of cecal and fecal flora.Results showed that in host metabolism,IOE inhibited BWG,energy intake,energy efficiency,glucose and lipid metabolism,lipid accumulation,body mass index(BMI)and relative mass of adipose tissue,and improved the TCA cycle and the degradation of nutrients,while IOP improves the TCA cycle and the degradation of nutrients,and reduces BWG,energy intake,energy efficiency,and glucose and lipid metabolism.In the intestinal flora,the administration of IOE improved the polysaccharide metabolism of the intestinal flora,as well as the relative abundance and propionate production of Bacteroides and Akkermansia;while the administration of IOP increased the polysaccharide metabolism function of the intestinal flora,as well as the relative abundance and butyrate production of Lactobacillus and Bacteroidales S24-7 group.After Spearman correlation analysis,the results showed that IOE enriched Bacteroides and Akkermansia,and caused an increase in the cecal propionate level;the propionate inhibited the host energy intake,which led to a decrease in BMI,relative mass of adipose tissue,BWG and lipid accumulation.IOP increased the levels of Lactobacillus and Bacteroidales S24-7 group,resulting in an increase in the cecal butyrate;butyrate promoted the host’s TCA cycle and the degradation of nutrients,and reduced BWG and lipid accumulation.(3)Study on the mechanism differences between IOE and IOP in HFD-fed miceIn order to understand the differences in the effects of IOE and IOP on HFD-fed mice,we compared the data of the two groups of mice at four time points(0,2,8,and 14 weeks).Results showed that the daily energy intake of the mice in the IOE group was significantly lower than that of the mice in the IOP group at week 2.After analyzing the flora,flora metabolism and host metabolism through multivariate statistics,we found that the effects of IOE and IOP on HFD-fed mice and intestinal flora are the most different at week 2.Compared with IOP group,in the host metabolism at week 2,the mice in the IOE group had lower levels of total BWG,daily energy intake,TCA cycle,and higher levels of substrate phosphorylation;in flora metabolism at week 2,Akkermansia and fatty acid elongation of the IOE group had higher levels,and the content of short chain fatty acids(SCFA)and triglyceride(TG)of the IOE group was lower.The intestinal flora uses fatty acid elongation to convert SCFA and TG into medium chain fatty acids(MCFA).It indicated that the effect of IOE on HFD mice may be due to the increase of Akkermansia and fatty acid elongation,which caused the enrichment of MCFA and the decrease of SCFA and TG,thereby decreasing the level of the host TCA cycle,increasing the level of substrate phosphorylation and inhibiting the host’s energy intake and BWG.In summary,IOE and IOP have produced different metabolite profiles by regulating the metabolism of the intestinal flora,and improved the metabolism of HFD mice.These results provide data and theoretical basis for the use of IOE and IOP,and help to establish the use strategy of Inonotus obliquus extracts and to develop new functional foods. |
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