| Background and Purpose Obesity is a state of metabolic disorder in which body fat accumulates too much and causes weight gain.In recent years,the number of obese people has grown rapidly worldwide,and a series of complications caused by obesity seriously threaten human health.At present,there are many methods to prevent and treat obesity,such as dieting,medicine,and bariatric surgery.However,these methods have large side effects and serious rebound of obesity after treatment.Therefore,it is necessary to find a safer and more effective obesity intervention method.Quercetin is a natural flavonoid commonly found in foods,and has various biological activities such as antioxidant,anti-cancer,and anti-inflammatory.Studies have shown that quercetin can effectively improve obesity,but its specific mechanism is still unclear.In recent years,studies have shown that obesity is closely related to intestinal flora.A high-fat diet causes intestinal flora disorder.The increase in the number of Gram-negative bacteria leads to an increase in lipopolysaccharide causing damage to the intestinal barrier.A large amount of LPS enters the blood through the intestinal barrier.The body’s metabolic endotoxemia leads to obesity and related metabolic diseases.Early experiments in our research group found that quercetin can regulate intestinal flora and repair mucosal barrier damage.Therefore,we speculate that quercetin may reduce LPS production and improve intestinal barrier function by regulating intestinal flora,relieve metabolic endotoxemia,and thus improve obesity and related metabolic disorders.This research intends to explore the mechanism of quercetin regulating intestinal flora and improving obesity induced by a high-fat diet.In addition,quercetin was used as a material to develop a quercetin compound prebiotic solid beverage,and to explore its best formula and its regulating effect on intestinal bacteria.This research provides a theoretical basis for quercetin to prevent and control obesity and related metabolic diseases,and also provides a basis for the application of quercetin in the development of functional foods.Methods 1 To evaluate the intervention effect of quercetin on high-fat diet-induced obese mice Obese mice are induced by high-fat diet.At the same time,mice are given different doses of quercetin by intragastric administration.The changes in body weight and food intake of mice are observed every day.After 20 weeks of intervention,the mice were dissected.The weights of adipose tissue and liver of each group of mice were compared,and pathological experiments were used to observe the size of fat cells and liver fat deposition of each group of mice to evaluate the effect of quercetin on fat accumulation in mice.The glucose tolerance test is performed to evaluate improvement of quercetin on insulin resistance in high-fat diet-induced obese mice.The blood lipid levels of mice in each group were detected to evaluate the improvement of quercetin on dyslipidemia in high-fat diet-induced obese mice.2 To evaluate the regulatory effect of quercetin on the intestinal flora of high-fat dietinduced obese mice 16 s r DNA sequencing of the intestinal contents of mice was conducted to analyze the abundance and diversity of the species of intestinal flora in each group of mice,and to analyze the changes in the levels and genus levels of intestinal flora of each group of mice,focusing on the analysis in the abundance of Gram-negative bacteria producing lipopolysaccharide.3 To evaluate the effect of quercetin on intestinal permeability and intestinal barrier function of high-fat diet-induced obese mice The content of LPS in the intestinal contents and serum of mice was detected by enzyme-linked immunosorbent assay(ELISA)to evaluate the effect of quercetin on LPS production.ELISA was used to detect the content of diamine oxidase and circulating D lactate in mouse serum,and to evaluate the effect of quercetin on intestinal permeability.The expression of tight junction proteins ZO-1,Mucin-2,Occludin,and Claudin in the mouse colon was detected by fluorescent quantitative PCR and Western blotting(WB)to evaluate the effect of quercetin on intestinal barrier function.4 To evaluate the inhibitory effect of quercetin on chronic inflammation in high-fat diet-induced obese mice The immunohistochemical experiment was used to observe the infiltration of inflammatory cells in the colon and adipose tissue of mice.The expression of inflammatory factors in the colon and adipose tissue of mice was further detected by fluorescent quantitative PCR and Western blotting.Finally,the activation of TLR4 / NF-kβ inflammatory signaling pathway was detected by Western Blotting.5 Development of quercetin compound prebiotic solid beverage and its regulating effect on intestinal flora Using sensory evaluation score as the standard,the best formula of quercetin compound prebiotic solid beverage was explored by single factor and orthogonal test.The growth curve of enterococci,enterobacteriaceae,bifidobacteria,and lactobacillus in the main materials and optimal formula of quercetin composite prebiotic solid beverage was determined by photoelectric turbidimetric method,to explore the proliferation effect of quercetin compound prebiotic solid beverage on some intestinal bacteria in vitro culture.Results 1 Intervention effect of quercetin on high-fat diet-induced obese mice Quercetin can significantly(p < 0.05)reduce the body weight of mice fed with high fat,and significantly(p < 0.05)reduce the fat accumulation in the adipose tissue and liver of mice.Quercetin intervention can improve the symptoms of dyslipidemia and insulin resistance in high-fat diet-induced obese mice.These results indicate that quercetin intervention can improve obesity and related symptoms induced by high-fat diet.2 Effect of quercetin on intestinal flora of high-fat diet-induced obese mice Quercetin intervention increased the community diversity of intestinal microorganisms in high-fat diet-induced obese mice,reduced the abundance of Gramnegative bacteria,including reducing the abundance of Enterbacter,which can produce LPS,and some microorganisms related to the occurrence of obesity,such as Adlercreutzia,Odoribacter and Brachyspira.Quercetin intervention also increased the abundance of some microorganisms related improving obesity,such as Akkermansia and Allobaculum,and some probiotics like Bifidobacterium and Lactobacillus.3 Effect of quercetin on intestinal permeability and intestinal barrier in high-fat diet-induced obese mice Quercetin intervention significantly reduced the content of DAO and D-lactate in serum(p < 0.05),and significantly increased the expression of tight junction proteins(ZO-1,mucin-2,occludin,claudin)(p < 0.05).The content of LPS in intestinal and serum of mice were also significantly reduced(p < 0.05).The results show that quercetin may reduce intestinal permeability by enhancing intestinal barrier function and reduce LPS in the intestinal contents getting into the blood circulation.4 The inhibitory effect of quercetin on chronic inflammation in high-fat diet-induced obese mice Quercetin intervention decreased inflammatory cell infiltration in colon and adipose tissue of obese mice,and decreased the expression of proinflammatory factors(TNF α,IL-1β and IL-6)significantly(p < 0.05).TLR4 / NF-κB inflammatory signaling pathway was activated in colon and adipose tissue of high-fat diet-induced obese mice.After quercetin intervention,the protein expression of this signaling pathway decreased.The results showed that quercetin intervention had an inhibitory effect on chronic inflammation induced by LPS.5 Development of quercetin compound prebiotic solid beverage and its regulating effect on intestinal flora The best formula of quercetin composite prebiotic solid beverage is: 8g of oligofructose,0.4g of quercetin,0.06 g of citric acid and 0.15 g of carboxymethylcellulose.The solid beverage has good sensory quality such as quercetin fragrance,moderate acidity and sweetness,uniform color and so on.Quercetin composite prebiotic solid beverage can inhibit the proliferation of Enterococcus and Enterobacter in vitro,and can effectively promote the proliferation of Bifidobacterium and Lactobacillus in vitro.Conclusions Quercetin may reduce LPS production by reducing the abundance of intestinal Gram-negative bacteria,at the same time enhance the intestinal barrier function,reduce intestinal permeability,reduce LPS entering the blood,relieve metabolic endotoxemia,and thus improve obesity,dyslipidemia and insulin resistance induced by high-fat diet. |
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