| Objective:Abnormal expression of 11β-HSD1 plays a critical role in the pathogenesis of Type 2 diabetes(T2D)and central obesity is a known risk factor of T2D.Mechanisms between 11β-HSD1 and central obesity remain unknown.In this present study,firstly,we studied the expression of 11(3-HSD1 in different adipose tissues from patients with central obesity, and analyse its correlation with risk factors of obesity.Methods:23 patients undergoing abdominal operation were divided into obesity group and control group according to BMI.The 11β-HSD1 expression in subcutaneous and visceral adipose tissues which were collected from these 23 patients were measured by RT-PCR and Western blots. Compare the indexes such as gender,age,body mass index (BMI),waist-to-hip ratio (WHR),serum lipids,blood pressure,Fasting blood glucose (FBG),Fasting plasma insulin (FIN),homeostasis model assessment of insulin resistance (HOMA-IR) and the expression of 11β-HSD1 from two groups. Evaluate the correlation of 11β-HSD1 mRNA expression in viceral adipose tissue with the risk factors of obesity.Results:Both groups had higher 11β-HSD1 expression in visceral adipose tissue than that in subcutaneous. The level of 11β-HSD1 in visceral adipose tissue from OB group was higher than that in CTL group,whereas no significant difference was found in subcutaneous adipose tissue between two groups. Spearman correlation analysis showed that the mRNA level of 11β-HSD1 level was positively correlated with BMI(r=0.4952, p<0.0001),WHR(r=0.5851, p<0.0001),FIN(r=0.2547, p<0.01),TC(r=0.1442, p<0.05),TG(r=0.1974, p<0.01),LDL-C(0.1529, p<0.05) and HOMA-IR(r=0.4637,p<0.0001), negatively correlated wiht HDL-C(r=-0.2659, p<0.01). Among the multiple factors, waist-hip ratio, body mass index and insulin resistance index are the most important variables that influence 11β-HSD1 expression in visceral adipose tissue.Conclusion:The expression of 11(3-HSD1 was significantly increased in visceral adipose tissue in patients with central obesity, which demonstrates that 11β-HSD1 may participate in the development of central obesity by visceral fat accumulation. The expression level of 11β-HSD1 in visceral fat tissue were related with BMI,WHR,FBG,FIN,HOMA-IR and HDL-C, among which WHR,BMI and HOMA-IR may be the most important variables that affected the expression of 11β-HSD1 in visceral adipose. Objective:11β-HSD1 participates in the development of central obesity by promoting visceral adipose accumulation, and insulin resistance index is one of the important factors which affect the 11β-HSD1 expression in visceral adipose. But the mechanism by which 11β-HSD1 involves in insulin resistance when obesity is still unknown. Numerous research show that dysfunction of adipocyte endocrining, inflammatory reaction and abnormal insulin signaling transduction pathways are involved in the pathophysiologic process of insulin resistance. Thus, in this section, we mainly research the impacts of 11β-HSD1 inhibitors on adipocytokines and insulin signal conduction pathway in obesity, and discuss the possible mechanism by which 11β-HSD1 participate in the formation of insulin resistance when obesityMethods:Male Wistar rats were divided into three groups randomly.The control group (CTL) were fed ordinary diet, obese group (OB) and 11β-HSD1 selective inhibitor-BVT.2733 groups (BVT) were fed high-fat diet for 12 weeks. Then BVT group were gavaged of BVT.2733 100mg/kg/d for 4 weeks. Serum glycemia and insulin levels at virous points were measured by intraperitonel glucose tolerance test, the adipocyte size and amouts were observed by H-E staining, the levels of plasma glucose and insulin were measured by biochemistry technology and ELISA. Adipocytokines such as adiponectin,leptin,resistin,TNF-αand IL-6 level were measured by ELISA. IRS-1,IRS-2,PI3K,GLU4 and PPAR-γexpression level in rat retina adipose tissue were analyzed by western blots.Results:Compared with CTL, the weight raised in rats with high-fat diet for 12 weeks(P<0.05), the level of plasma insulin insulin resistance,TNF-αand IL-6 increased obviously(P<0.01), the level of serum adiponectin decreased, and leptin and resistin increased(P<0.01). The size of adipocytes were bigger. Western blot shows protein expression level of IRS-1,IRS-2,PI3K and GLU4 in retinal adipose tissue reduced significantly, and PPAR-γincreased clearly(P<0.01). Giving intervention for 4 weeks, compared with OB, the rats' weight lessened, the adipocyte size reduced, fasting plasma insulin and insulin resistance level decreased obviously (P<0.05), the level of serum adiponectin rise, as well as the protein expression level of IRS-1,IRS-2,PI3K and GLU4 in retinal adipose tissue, and PPAR-γexpression reduced(P<0.05), but there was no significant differences in the level of serum leptin and resistin between OB and BVT group. Also, the differences in the level of plasma glucose,serum leptin and resistin between three groups have no significance. Glucose tolerance test shows that there was no obvious difference in the level of fasting glycemia from three groups, but the glycemia levels at various time points after glucose load in OB group were increased significantly. The glycemia level at 15 min after glucose load in BVT group decreased obviously, while no distinct changes at every other time points. The insulin levels at every time point in OB rats were significantly higher than those in CTL group, and dropped severly after intervention.Conclusion:11β-HSD1 selective inhibitor BVT.2733 could improve insulin resistance in obesity rats, which plays its role mainly by increasing the endocrine of adiponectin, decreasing the level of TNF-αand IL-6, decreasing PPAR-γexpression in adipose tissue for supressing the differentiation of adipocytes and upregulating insulin signaling transduction pathways of IRSs/PI3K/GLU4.
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