Studies On The Influence Of Fructose-drinking High-fat Dyslipidemia Model Of Syrian Golden Hamster

BackgroundIn recent years, as the improvement of living standards, reducing labor and increasing aging population the proportion of diabetes in the world showed a sharp rise in the prevalence of the trend of diabetes. Diabetes has become one of the culprit of malignant tumors which decline hunman health level, that after heart and cerebrovascular diseases. Currently more than 240 million people around the world have been diagnosed with diabetes, experts predict that in 2025, there is estimated to be more than 3.5 million people suffer from diabetes. What published in 2009 saying, "China epidemiological survey of diabetes and metabolic syndrome, the latest data show that over the age of 20 cities, towns and prosperous rural population, diabetes prevalence has reached 9.7%, plus 15% in glucose regulation stage. If do not take effective means for prevention and treatment, diabetes may become the 21st century new disaster.Fructose (Fructose, FRU) generally made of crystal or syrup for commercial purposes. In the past 20 years, as a sweetener in processed foods and soft drinks fructose increased from 20% to 30%, which increase similar to is the rate of increasesing obesity over the same period. Some studies suggest that daily high-fat diet, drink plenty of soft drinks, fructose caused overweight and obesity, high fat and high fructose induced hypertriglyceridemia is closely related to metabolic syndrome, impaired glucose tolerance, insulin resistance. However, how higher fructose cause triglyceride, non-alcoholic fatty liver disease, and insulin resistance, insulin sensitivity which was followed by impaired glucose tolerance, the related molecular mechanism has not been fully elucidated. Therefore, this study further clarify the mechanism and the mechanism for its take appropriate interventions to prevent obesity, diabetes and metabolic syndrome is of great significance. And their further study of the pathogenesis related to a need for a modern dietary patterns with similar glucose and lipid metabolism are similar to animal and human models. With previous literature suggests, rabbit, rat or mouse models of human lipid metabolism are very different, less blood in mice, is not conducive to biochemical analysis and experimental design, the use of such animals as the study of modern society, human high- sugar high-fat diet in animal models, with some limitations. On the other hand, studies have shown that Syrian hamster, especially the male hamster, glucose and lipid metabolism in the nearest human, therefore, this study is more similar to human lipid metabolism in the golden hamster as experimental animals, give 12 weeks of the different components of the high fat, sugar fat diet, observed hamster body weight, serum glucose and lipid metabolism, insulin, serum lipid fatty acid binding protein, the insulin sensitivity, liver index, liver and observed pathological changes of pancreatic tissue. Look closer to human due to the high sugar and fat diet caused abnormal lipid metabolism and insulin resistance in animal models. As obesity, metabolic syndrome, hypertriglyceridemia, diabetes, non-alcoholic fatty liver mechanism and early intervention (such as drug screening, nutritional factors, dietary intervention, etc.) to provide a new animal model.Considerable evidence that adipose tissue is not only the energy storage is more important endocrine organ, releasing a large number of biologically active substances into the blood stream. These adipose tissue-derived bioactive molecules, through the local and systemic role in coordinating energy metabolism, insulin sensitivity, inflammation and vascular response. Fat-type fatty acid binding protein (Adipocyte fatty acid binding protein, A-FABP) expressed mainly in fat cells and macrophages, as fatty acid transport protein, affecting the metabolism of fatty acids and fatty acid signal, with diabetes and atherosclerosis are closely related. Mature fat cells is the largest protein [2], fatty acid binding protein is a member of the family, between the fatty acid transport in cells and plays an important role in energy metabolism [3,4]. Recently, animal models suggest A-FABP may function in the automatic adjustment of sugar have an important role. In recent years, studies have found that glucose metabolism and A-FABP levels were significantly related. In this study, by detecting the A-FABP in different dietary groups, and to explore with the blood sugar, insulin resistance, insulin sensitivity, the correlation between reduced.In summary, our study group selected Syrian hamster as the research object, feed ingredients by high fat diet induced in different ways, the establishment of the modern dietary components closer to the animal model of lipid disorders, the current diabetes, obesity, metabolic syndrome, hypertriglyceridemia, non-alcoholic fatty liver disease pathogenesis and animal models of early intervention research. And also understand the feeding conditions in the different dietary concentrations of A-FABP was studied with insulin resistance.Purpose1. Through different components of diet to fed Syrian golden hamsters, establish a animal model which is close to modern human diet, the Syrian hamster is fat and high fructose, fatty liver, lipid metabolism model, and compare different diet components fed to the golden Hamster model of glucose and lipid metabolism. 2. To explore the normal control group (N), high-fat group (HF), high fat+ glucose group (HF+GLU), high fat+fructose group (HF+FRU).Check the Syrian hamster body weight, serum glucose and lipid levels, Insulin, A-FABP levels, liver index and morphological changes in liver and pancreas. Compara and analysis the normal and pathological conditions changes the Syrian hamster and its glycolipids possible mechanism.Methods1. Randomly selected 12 male Syrian golden hamsters, divided into four groups, n= 6. The normal control group (fed with normal diet), pure fat group (fed with high fat diet alone), glucose fat group (with 20% glucose solution+high fat diet sugar), fructose, high-fat group (with 20% fructose solution+high fat diet). Were fed for 12 weeks, respectively, measured at 0,1,2,6,12 weeks, body weight, enzymatic determination of hamster serum triglycerides, cholesterol, blood sugar levels.2.12 over the weekend killed hamster, exposure to the abdominal cavity, heart blood 3-4mL, room temperature for 30min 3000rP Centrifuge 15min, the plasma stored at -80℃10μL refrigerator equipment seized. Visual observation of liver and pancreas, liver weight, liver index (HSI=liver mass/body mass×100%). Specimens from the liver lobe, separating the pancreas,10% formaldehyde solution immediately put into a fixed, sequential ethanol dehydration, xylene, paraffin embedded sections, HE staining were observed under light microscope hamster liver.3.ELISA method hamsters in each group serum concentrations of insulin and A-FABP:American R & D companies in serum A-FABP and serum insulin kit kit, in strict accordance with manual operation,11% of intra differences, differences between batches 10%. Using enzyme-linked immunosorbent assay of serum A-FABP and insulin concentrations. Insulin sensitivity index:insulin sensitivity index ISI= LIN 1/(fasting plasma glucose FBG×fasting insulin levels FIN). 4. Statistical analysis:SPSS 13.0 statistical software to analyze data toⅩ(-)±s that homogeneity of variance with multiple comparison one-way ANOVA, multiple comparisons between groups using LSD method, missing the test with Welch, by Tamhane multiple comparison test was used to compare different time indices repeated measures analysis of variance. P<0.05 considered significant difference.Results1. Fed different dietary components Syrian golden hamsters in each group changes of body weight:The average body weight of water continued to rise, reached the peak at 12 weeks. HF group, HF+GLU group, HF+FRU group compared with the increase of N greater (P<0.01). Each time point compared with HF+FRU body weight than the other three groups (P<0.01).2. Composition of different dietary groups fed Syrian golden hamsters of the blood biochemical characteristics:TG:N Group 12-week triglyceride levels flat. HF group was significantly higher 2 weeks,6 weeks down to 12 weeks increased significantly. HF+GLU group has continued to rise,12 Zhou Dafeng value. HF+FRU group increased at 2 weeks Da Houda to a platform, reached the peak at 12 weeks. Group into four groups no significant difference in triglyceride levels, one week after feeding different dietary ingredients before, each time point are HF+FRU triglyceride was higher than other three groups (P<0.01).Cholesterol:HF group, HF+GLU group and HF+FRU cholesterol were significantly increased after 1 week, HF+GLU group and HF group reached a peak in 2 weeks,6 weeks and 12 weeks fell slightly. HF+FRU group process continued upward trend,12 Zhou Dafeng value. HF group, HF+GLU group, HF+FRU group into the group of cholesterol from 2mmol/L up to 12 weeks is about 7.5mmol/L, while the normal group from remaining at 1.95 or so. HF group, HF+GLU group, HF+FRU group of cholesterol increased significantly in the normal group (P<0.01).Glucose:normal groups during the 12 weeks no significant changes in blood glucose (P> 0.05). HF, HF+FRU, HF+GLU group and normal glucose range of different levels of blood glucose changes, blood glucose in the 12 weeks maximum, minimum,0 weeks, which significantly increased at 1 week,6 weeks after elevated platform, where the HF+FRU group than in blood sugar range HF, HF+GLU group more significantly (P<0.01).3. Hamsters in each group morphological changes in liver and pancreas:Liver:the naked eye:normal no abnormal changes in liver; HF group and HF+ GLU group of liver color yellow purple intersection, blunt the edge of some sand-like surface of the liver changes, the volume increases; HF+FRU group of hamster liver was yellow and white brown, liver volume increased significantly, blunt edge, coated tension. Light microscopy:the normal control group, no significant morphological changes. HF group and HF+GLU group, swelling of liver cells was increased, there is a large number of lipid droplets, some vacuolization of liver cells, liver interlobular vein central vein and a small amount of red blood cells, liver cells, see inflammatory cells; HF+FRU group and the HF and HF+GLU group compared to significant changes in fat-like, fat droplets accumulate most of the diffuse lobular nuclei stained cells were significantly swollen, irregular arrangement of hepatic cells, see a large number of inflammatory cells, and capsule formation of visible fat.Pancreas:no significant difference in the naked eye, light microscopy:the normal control group, the number of normal islet size, size uniformity, shape rules, clear boundaries; HF group, HF+GLU group, HF+FRU group of islet hyperplasia, the volume generally increases, the number of increased, but differences among the three groups was not significant. 4. Liver Index:Compared with normal group, HF group, HF+GLU group, HF +FRU group, the liver index:(liver index=liver mass/body mass Water 100%) was significantly higher, the difference was significant (P<0.01); with the HF group, HF +GLU group, HF+GLU group more significantly elevated levels of liver index (P <0.01).5. Insulin and insulin sensitivity index:Serum insulin:HF group, HF+GLU group, HF+FRU in the serum insulin levels were higher than the control group, with HF and HF+GLU group, HF+FRU group more significantly elevated insulin levels (P<0.01.) Insulin sensitivity index:insulin sensitivity index [ISI=LIN 1/(fasting plasma glucose FBG×fasting serum insulin FIN)]:HF group, HF+GLU group, HF+FRU group were lower than the N group, the difference was significant (P<0.01), in which HF+FRU group and HF group, HF+GLU group, a lower insulin sensitivity index, the difference was significant (P<0.01).6. Serum A-FABP:Serum A-FABP:four hamster serum A-FABP levels, HF group, HF+GLU group, HF+FRU serum A-FABP concentrations were higher than N group, the difference was significant. One group and HF HF+FRU group, HF+GLU group, higher serum A-FABP levels, the difference was significant, P values were<0.01.Conclusion1. After a certain period of different components of the high fat diet, the Syrian hamster can form the typical dyslipidemia, hyperglycemia, insulin resistance, non-alcoholic fatty liver and islet hyperplasia. Among them, high-fat high-fructose hamster model group and model group and model group, high fat compared with high glucose, triglycerides, cholesterol, blood sugar, increase insulin secretion, insulin sensitivity significantly decreased, non-alcoholic fatty liver and more significant phenomenon of islet hyperplasia.2. High-fat and high fructose male hamster model can simulate the human dietary ingredients and dietary glucose and lipid metabolism disorders of human pathological process better, the modern high-fat high-fructose diet caused impaired glucose tolerance, fat lipids, research of metabolic syndrome advantage of the experimental animal models.3. Serum A-FABP levels increased in group which insulin secretion increase, insulin sensitivity decrease, reduce fat and high fructose more significant to a significant increase in the rat group, the serum A-FABP may be diabetes, metabolic syndrome, the occurrence and development of a marker.