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Study on Effects of Adipocyte Differentiation in Improvement by Sports on Insulin Resistance in High-fat-diet Rats

Author: ChenYuJuan
Tutor: HeYuXiu
School: Hebei Normal
Course: Physical Education and Training
Keywords: Adipocyte differentiation Insulin resistance Insulin sensitivity Treadmill Exercise Fat diet
CLC: R587.1
Type: PhD thesis
Year: 2010
Downloads: 243
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Abstract


Insulin resistance refers to the amount of insulin secretion at normal levels, the target cells to stimulate glucose uptake and utilization was significantly reduced physiological effects, or target cell uptake of glucose to maintain normal physiological effects of the extraordinary amount of insulin needed. It is the development of type 2 diabetes in the event of an important feature of the process is the key to the metabolic syndrome, obesity, hyperlipidemia, hypertension and cardiovascular disease are closely related. Studies have shown that adipose tissue and insulin resistance are closely linked. Obesity causes abnormal fat cell differentiation, cell hypertrophy, leading to insulin resistance. Also causes abnormal differentiation of adipose tissue lipolysis process adipocytes from insulin resistance, a large number of FFA from adipose tissue secreted into the blood, and thus the insulin sensitivity in other tissues and organs affected. Adipose tissue can secrete resistin, inflammatory cytokines and other substances to regulate the body's energy metabolism in insulin resistance plays an important role in the development process. It can be inferred that the normalization of adipocyte differentiation is the key to improving insulin resistance. From exercise on diabetes prevention research can be found, indeed played a sport to improve insulin resistance, diabetes prevention and treatment efficacy. Some experimental studies have confirmed that adipose tissue insulin resistance may be the initiating site, then the fat cell differentiation in the movement to improve insulin resistance is connected to play the role? Differentiation of insulin resistance which changes will have an impact? Adipocyte differentiation through in motion the changes affecting insulin resistance can learn more about its internal mechanisms. Therefore, this study aims to: explore the molecular mechanism of adipocyte differentiation, adipocyte differentiation and analysis of a series of morphological and functional changes in the impact of the role of insulin resistance, and further improve the understanding of adipocyte differentiation motion abnormalities and insulin resistance mechanism for prevention and treatment of obesity-related metabolic syndrome exercise prescription formulation provides the necessary theoretical basis. This study was designed to investigate animal fat diet and exercise training on rat adipocyte differentiation and insulin resistance, and to analyze changes in adipocyte insulin resistance formation mechanism. On the one hand in the rat model of insulin resistance in high-fat dietary intervention given during the formation of treadmill training performed by comparing the model group and the intervention group, fasting blood glucose, serum insulin levels, insulin sensitivity index, resistance index and other indicators to determine Treadmill on improvement of insulin resistance, simultaneous detection of adipose tissue differentiation, adipose tissue differentiation markers transcription factor PPARγ and C / EBPα protein expression, comparing the number of fat cells and volume slicing differentiation indicators and associated testing, explore adipocyte differentiation in motion improve the mechanism of insulin resistance; hand formation in a rat model, select the different stages of testing at different times treadmill training and high-fat dietary intervention rat adipose tissue differentiation of each index changes, so as to explore different factors on intervention the role of adipocyte differentiation, and thus a preliminary understanding of adipocyte differentiation stage variation for adipocyte differentiation and insulin resistance provide evidence to clarify the relationship. Part 8 weeks treadmill running high fat diet rat adipocytes differentiation and insulin sensitivity in Sprague-Dawley (SD) inbred male rats were randomly divided into four groups: control group (C) 10 only, and feed In normal diet, without treadmill training; fat group (H) 10 only, and fed with high fat diet, without treadmill training; fat exercise group (HE) 10 only, and fed with high fat diet for treadmill Training (60min / d, running speed 20 m / min, 5d / w); exercise group (E) 10 only, and fed with normal diet for treadmill training. 8 weekend killed, compared to each group fasting blood glucose, blood insulin levels and insulin sensitivity index (ISI), resistance index (HOMA-IR) and other indicators to determine treadmill training on insulin resistance improving effect, simultaneous detection of adipose tissue differentiation, adipose tissue differentiation markers transcription factor PPARγ and C / EBPα protein expression of adipocyte sliced ??compare the number and volume of such differentiation index, the results are as follows: 1, serological indicators: each group glucose concentration was no significant difference (P gt; 0.05) ; H serum insulin concentration with C group and HE group were increased compared to the trend, but did not reach significant difference, E group than in group C, H group and HE group, the differences were significant (respectively P lt; 0.05 , P lt; 0.01, P lt; 0.05,); H ISI and HOMA-IR group compared with C group had significant difference (respectively P lt; 0.01 and P lt; 0.05), H group than HE ISI group, E group than in C group and HE group, but not statistically significant difference; HOMA-IR in the highest group H, E group than in C group and HE group showed no significant difference. 2, the protein expression of adipose tissue: PPARγ: E group than in C group, the difference was significant (P lt; 0.01), showed that exercise can promote PPARγ increases. H group was higher than in group C, HE group than in group H is low, but were not statistically significant. C / EBPα: H group was higher than the other groups, the difference was highly significant (P lt; 0.01); E group was higher than in group C, HE group than in H group, suggesting that exercise can promote C / EBPα increases. PI3K: E group than in C group, the difference was significant (P lt; 0.05); H group than in the group are high, with the C group, HE group differences were statistically significant (respectively P lt; 0.01, P lt; 0.05); E group than in the HE group, but not statistically significant, the overall show exercise can promote PI3K expression. PKBser473: highest to Group H, C group than in group E, each group had no significant difference in the performance trend with PI3K. 3, adipose tissue differentiation, proliferation index adipocyte differentiation: E group was the highest, and the difference compared with the other groups was significant (P lt; 0.01), HE group than in Group H, H group, slightly higher than in group C However, there was no significant difference. Proliferation index: C group was the highest, with H and E group compared with the significant difference (respectively P lt; 0.01 and P lt; 0.05); HE group than in group H and E group (P lt; 0.05). 4, fat cell morphology: E group of fat cells smaller than C group, the difference was significant (P lt; 0.01), higher than the number of cells in group C; H group were smaller than in group C (P lt; 0.01), the number of also increased (P lt; 0.01), prompted high-fat diet on fat cell morphology changes, but compared with the motion effect, in combination with other indicators to analyze needs; HE group compared with the group H larger fat cells (P lt; 0.01), and the number decreased. 5, rat adipose tissue ISI and the correlation analysis of the indicators: ISI and HOMA-IR value of r reaches -0.97. In insulin resistance indicators, PI3K with ISI correlation coefficient of 0.50, while PKB is only -0.04; while in adipocyte differentiation-related indicators, with significant differences in indicators of visceral fat pad weight and visceral fat%, correlation coefficients were -0.42 and -0.39, fat cell differentiation, proliferation index, PPARγ, adipocyte diameter, area, volume and other indicators of low correlation with ISI; C / EBPα moderate correlation with ISI, the correlation coefficient is - 0.55; fat cells showed high correlation with ISI, a correlation coefficient of 0.95. The second part of the different stages of the campaign and the intervention of high-fat fed rats adipocyte differentiation-related changes in Sprague-Dawley (SD) inbred male rats 160, divided into four stages experiments (2,4,6,8 weeks) Each stage of 40 rats were randomly divided into four groups: control group (C) 10 only, and fed with normal diet, without treadmill training; fat group (H) 10 only, and fed with high fat diet, without Treadmill Training; fat exercise group (HE) 10 only, and fed with high fat diet for treadmill training; exercise group (E) 10 only, and fed with normal diet for treadmill training. The stages are drawn, serum TG, TC, FFA, HDL, LDL and other indicators, adipose tissue differentiation, adipose tissue differentiation markers transcription factor PPARγ and C / EBPα protein expression of adipocyte number and volume slicing compare other related differentiation indicators, the results are as follows: 1, various stages of rat visceral fat pad weight, relative weight: 2 weeks group C and group E group had no significant difference, H group than HE group, the difference was significant (P lt; 0.05), H group was higher than in group C, but no significant difference; 4 weeks group H group was higher than in group C (P lt; 0.01), HE group than in group H, E and C group no difference between, E group is slightly lower; six weeks the exercise group were lower than their corresponding control groups (C vs E, P lt; 0.05; H vs HE, P lt; 0.01), C group was higher than Group H, but no statistical significance; 8 weeks low exercise group exercise its corresponding control groups (P lt; 0.01), H group was higher than C group, the difference was significant (P lt; 0.01). Group C and E along with the extension of the number of weeks were gradually increased, while the H group and HE group appeared after first increased and then decreased sharply rising trend. 2, serum markers: H group TC, TG, LDL, FFA were higher than in group C and HE groups at different stages are performed very remarkable and significant differences (P lt; 0.01 and P lt; 0.05), HDL appears up - down - up trend in 4 weeks with significant difference (P lt; 0.01); E group, in addition to HDL, FFA outside each index lower than C group, only two weeks LDL performance significantly different (P lt ; 0.01). 3, adipocyte differentiation: 2,4,6 weeks in each group had no significant difference compared to 8 weeks E group than the other groups (P lt; 0.05), HE group also increased, but not statistically significant . Longitudinal comparisons, C and H groups were little changed; HE group and E group were increased to a greater increase in group E (P lt; 0.01). 4, adipose tissue proliferation index: 2 weeks proliferation higher proportion of each group, but no significant difference compared with each other, in which the highest group H, E group was the lowest; 4 weeks, E group than in C group, the difference was significant (P lt; 0.05), H group, and HE, C was no significant difference between the groups; six weeks in each group showed no significant difference, but each group E group was still slightly higher, HE set slightly lower than the group H; 8 weeks Group E lower than the C group, the difference was significant (P lt; 0.05), HE than H group, and the difference was significant (P lt; 0.05), H group than in C group, the difference was significant (P lt; 0.01 ). From the longitudinal comparison, in the two weeks each group have higher levels of 4,6,8 weeks decreased significantly stabilized; fell the most obvious is H groups. 5, adipose tissue PPARγ protein expression changes: 2 weeks E group than in the group, with each group were significantly different (P lt; 0.01), among other groups had no significant difference, HE was the lowest; 4 weeks each group showed no significant difference, but still higher than in group C Group E, HE group slightly higher than H group, but no significant difference; six weeks, each group comparison still no significant difference, E groups slightly higher than C group, HE group were lower than H; eight weeks the exercise group compared with the corresponding control group, E group compared with C group difference was significant (P lt; 0.01). From the longitudinal comparisons, C group showed a gradual upward trend to six weeks time and decreased slightly; H group and HE group showed an increased gradually and the HE group increased considerably; E group decreased first and then increased Trends. C / EBPα changes: 2 weeks E group was the highest, and with each group having a highly significant difference (P lt; 0.01), C group was the lowest, H group than in C group, but the difference was not statistically significant, HE group of high in the H group, the difference was significant (P lt; 0.05); 4 周 each group had no significant difference, E group than in group C, HE group than in group H, H group was still higher than in group C; 6 weeks, each group still no significant difference compared to the exercise group were slightly higher than the corresponding control group, H group, slightly lower than in group C; 8 weeks group H C / EBPα increased dramatically higher than other groups, and C group, the difference was significant (P lt; 0.05), E group was higher than in group C, HE group than in the group H is slightly lower. From the longitudinal comparisons, C group continued to show an upward trend, the highest in eight weeks; H group and C group trend is basically the same, but fell back in six weeks, to a sharp increase in the first eight weeks; E was generally high in Group C, but in 2-6 weeks basically in decline, recovering somewhat to eight weeks, but did not reach the level at 2 weeks; HE group and E group changes in posture basically the same, but in the first eight weeks of the dramatic increase over when the level of the two weeks. 6, fat cell morphology: two weeks in Group E adipocytes smallest, the largest number of H group and HE group with significant difference (P lt; 0.01), H group than in group C cell volume, cell number less, the difference was highly significant (P lt; 0.01), HE group were higher than the number of H group (P lt; 0.01), cell volume is greater than the H group, but the difference was not statistically significant; 4 weeks of each group Item No significant difference, E group were higher than the volume and number of cells in group C, HE cells volume is greater than H, the number of cells smaller than the H group, H group, C group than the number of cells, the cell volume is less than group C ; 6 weeks Group H cell number and volume were higher than in group C, but the difference was not significant, the number of cells in the exercise group and volume were higher than their corresponding control group, E group's cell number and volume were greater than HE group, in which the number of the difference was significant (P lt; 0.05); 8 week group E cells smaller than in group C (P lt; 0.01), number of fat cells than in group C, HE group volume is greater than H, a small number, the difference was highly significant sex (P lt; 0.01); H group is higher than the number of fat cells in group C, the volume is less than the C group, the differences were highly significant (P lt; 0.01). Longitudinal comparisons, C group cell volume increased volatility trend, the highest in eight weeks; H group first and then decreased steadily recovering; E group in 2-6 weeks basically in decline, recovering somewhat to 8 weeks , but did not reach the level at 2 weeks; HE group and E group changes in posture basically the same, but in the first eight weeks of the dramatic increase over the two weeks when the level. Conclusion 1,8 week high-fat diet can reduce insulin sensitivity, resulting in insulin resistance phenomenon, its possible mechanism as follows: ① increased body weight and visceral fat weight; ② reducing intracellular fat synthesis, increased serum TG and TC; ③ excessive increase in adipocyte differentiation transcription factor PPARγ and C / EBPα expression, abnormal differentiation of fat cells; ④ reduce proliferation of adipose tissue, but the accumulation of fat cells to a larger base, make fat cell volume preparation; ⑤ abnormal increase in serum FFA, may increase their insulin resistance. 2, the movement caused by high-fat diet can improve insulin function decline, which could improve mechanisms as follows: ① reduce body weight and visceral fat weight; ② increase in intracellular fat synthesis, decreased serum TG and TC; ③ increased adipocyte differentiation transcription factor PPARγ and C / EBPα expression, and promote adipocyte differentiation capacity enhancement; ④ improve adipose tissue proliferation, increased number of fat cells, reducing the size of fat cells; ⑤ increase in serum FFA, promote body fat metabolism. 3, the role of exercise and high-fat diet will take some time to accumulate, each index change in four weeks and six weeks inflection point.

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