| BackgroundWith the change in diet and the increase in consumption of high-carbohydrate, the prevalence of clinical metabolic diseases also increased, which is seriously harmful to health. Epidemiological data indicated that excessive consumption of nutritive sweeteners is closely related to the high incidence of metabolic diseases. At the present, sucrose, fructose, glucose and lactose are common nutritive sweeteners. They are consumed in large amount from foods and beverages. However, how these sweeteners have an effect on the metabolism, such as uric acid, glucose and lipid level? And, which kind of nutritive sweetener has the serious effects on the body? It needs for further study. Moreover, the efficacy that inulin can improve metabolic diseases has been confirmed all over the world. Nevertheless, for the metabolic changes in rats induced by sweeteners, the specific intervention mechanism of inulin still remains to be further clarified.ObjectivesFirstly, to elucidate the effects of different types of sweeteners on metabolism of uric acid, glucose and lipid in rats, and to make clear the type which can seriously influence metabolic disorders, aiming to provide a scientific basis for a reasonable diet.Secondly, according intestinal flora macro-structure and micro quantities, the activity of uric acid-related enzymes, lipid metabolism related enzymes, and glucose-related indicators, aiming to explain the possible pathological mechanisms of metabolic changes induced by different sweeteners.Thirdly, to clarify the inulin effect of improvement and intervention of sucrose-induced metabolic disorders, and to provide reference and basis for the improvement of clinical intervention of chicory for the metabolic disorders induced by sweeteners.MethodsPathological basic research of metabolic changes induced by four kinds of nutritive sweeteners:Pathogenesis inducement method was used to simulate the change of clinical dietary structure, aiming to investigate the influences of four different types of sweeteners on uric acid, glucose and lipids metabolism in rats and to identify the major pathogenic type of sweetener. The study investigated the development process and possible pathogenic mechanism of metabolic disorders induced by four kinds of sweeteners by biochemical, enzymatic, enzyme-linked immunoassay, polymerase chain reaction and etc.Intervention study of treatment with inulin in metabolic diseases induced by sucrose:The research used multi-disciplinary techniques, including the overall level, organ level, molecular level and microbiological level. The study utilized uric acid metabolism key enzyme XOD, ADA, the key enzymes in lipid metabolism HL, LPL, FAS and NEFA, glucose and related indicators FINS, DPPâ…£, and intestinal flora as a starting point. With enzymatic, ERIC-PCR fingerprinting and QPCR methods, the study aimed to analyze intervention of inulin on metabolic disorder and the possible mechanism.ContentsThe research consists of literature review and experiment.Literature Review includes two aspects:research progress of nutritive sweeteners and metabolic diseases, the research of intestinal flora and diet.Experimental research mainly includes the following two chapters.The first chapter is that effects and mechanism of four kinds of nutritive sweeteners on metabolism of uric acid in rats. Based on epidemiological investigation and preliminary laboratory work, the study expanded the research on influence of uric acid, glucose and lipid metabolism by consuming four different nutritive sweeteners. In this part, four common nutritive sweeteners are dissolved in water and drunk by rats for a long time. The following laboratory parameters will be dynamically observed weekly to clarify the pathological features of metabolic changes induced by different kinds of sweeteners and to find out the most serious one:weight, waist circumference, blood glucose, uric acid, cholesterol and etc. On the basis of metabolic changes induced by sweeteners, pathogenesis of metabolic disorders induced by four kinds of sweeteners will be discussed from intestinal flora and metabolism-related enzyme activity levels.The second chapter is that the research of inulin treatment on metabolism disorders induced by sucrose in rats. On the basis of pathological studies, intervention of inulin is carried out. Sucrose played an important role in metabolic disorder and was chosen as model inducer during the experiment. By observing parameters of weight, waist circumference, blood glucose, uric acid and cholesterol, improvement was investigated in sucrose-induced metabolism disorders on metabolism of uric acid, glucose and lipid. From the perspective of intestinal flora macro-structure and micro-quantities, uric acid, glucose and lipid-related activity index, intervention mechanism of inulin is investigated.Results1. High glucose, sucrose drinking water can significantly increase the weight of rats, fructose and lactose had no significant effect on body weight. The intake of fructose, glucose and sucrose can lead to a significant increase in abdominal fat weight and abdominal circumference of rats. Serum triglyceride levels were significantly constantly increased. Overconsumption of fructose and sucrose can induce elevation of serum uric acid in rats, while lactose ingestion reduced serum uric acid. In addition to fructose, the remaining nutritive sweeteners can raise glucose level. These results suggested that sucrose can lead to glucose, lipid and uric acid metabolism disorders and play an important role in metabolism on rats. Besides, fructose, glucose, sucrose can reduce the rat HL activity and increase FAS and NEFA levels, indicating that the effect of the three sweeteners on blood lipid is associated with synthesis and catabolism of fat.Fructose and sucrose can increase serum XOD activity. Sucrose may increase serum ADA activity while lactose may decrease it. These results indicated that the effect of fructose, sucrose and lactose on uric acid is associated with metabolic changes of uric acid pathway enzymes. Glucose, sucrose, lactose can increase IR and DPP IV in intestine, indicating that effect of glucose, sucrose and lactose on blood glucose elevation is associated with DPPIV content increasing, at the same time, these sweeteners can lead to insulin resistance. After intake of sweeteners, intestinal microflora and quantity changes, the number of E. coli bacteria sweetener group were increased, lactose group probiotic Bifidobacterium longum number increased significantly. In addition to lactose group, Lactobacillus acidophilus of other groups was significantly increased, indicating that may have an impact on the intestinal flora after the intake of sweeteners. Nutritive sweeteners may change intestinal flora, thereby affecting metabolic pathways of glucose, lipid and uric acid related enzymatic activity, leading to changes in metabolism.2. Inulin can significantly improve pathology including the increase of body weight, abdominal circumference and abdominal fat induced by sucrose water. At the same time, inulin can also significantly reduce uric acid, triglycerides, total cholesterol and glucose levels, suggesting that inulin has improved multi-functional activity of metabolic disorders. Inulin can reduce the ADA and XOD activity, suggesting that the effect of lowing uric acid may be associated with direct regulation of uric acid-related enzymatic activity. In addition, inulin can decrease FAS, NEFA in liver, while HL activity can be significantly increased, suggesting that the decrease on blood lipid of inulin by inhibition of lipid production and promoting lipid decomposition. Inulin can reduce the sucrose-induced increase in insulin levels and intestinal tissue DPPIV content, suggesting that inulin can play a similar role with DPP IV to lowing sugar content of blood. Inulin can improve the intestinal microflora and significantly reduce the number of E. coli bacteria conditions. Inulin can also increase the probiotic Bifidobacterium longum and Lactobacillus acidophilus number, indicating inulin can improve intestinal microflora. Inulin may decrease key enzyme activity related to glucose, lipid and uric acid metabolism to improve metabolism disorders by improving the intestinal microflora, increasing the number of probiotics and reducing the number of harmful bacteria.Conclusions1. Four different types of nutritive sweeteners can affect the metabolism of rats, of which sucrose affect glycolipid uric acid metabolism is more serious. Uric acid lipid metabolic changes caused by nutritive sweeteners are closely related to enzymatic activity changes of uric acid, Lipid synthesis and catabolism-related activity decreased, elevation of insulin and DPP â…£ and changes of Intestinal microflora and quantity.2. Inulin can significantly improve the glycolipid uric acid metabolism induced by sucrose drinking. Inulin also reduce the uric acid enzyme activity and lipid biosynthesis-related indicators, elevating blood lipid catabolic enzymes HL activity, at the same time, lowing insulin levels and DPP â…£ content. For the sucrose-induced intestinal microflora and quantity changes, inulin plays a significant regulatory role. The effect of inulin improve metabolic disorders may be associated with regulation of intestinal flora, changes of uric acid lipid metabolizing enzyme activity and content.Innovation1. The study firstly discussed and compared of impact on uric acid metabolism of fructose, glucose, sucrose and lactose and sucrose was found to effect metabolism disorders more seriously.2. In this study, from the perspective of the intestinal flora, macroscopic and microscopic changes of intestinal flora caused by sweeteners are in comparative studies, providing a new perspective on research of pathogenesis of metabolic disorders induced by sweetener consumption diet-induced structural changes.3. Sucrose as the model inducer, from different levels of the intestinal flora and uric acid lipid metabolism related enzymes, clarifying the intervention mechanism of inulin prevention of metabolic disorders for the first time. |
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