| Background:Epidemiological data showed that long-term ethanol consumption was one of the most important - and potentially one of the most avoidable-risk factors for chronic disease and injury, but it is increasingly becoming a serious problem worldwide. It has been documented that chronic heavy ethanol consumption directly impairs glucose tolerance and insulin sensitivity, which are the major pathogenicfeatures of type 2 diabetes mellitus(T2DM). Although the precise mechanism or mechanisms underlying the effect of alcohol on the pathogenesis of T2DM has not been well elucidated as of yet, recent findings indicate that there is a clear link between T2DM and the alcohol-elicited dysfunction of white adipose tissue (WAT).Traditionally, WAT has been considered only a passive reservoir for energy storage, but the discovery of a number of adipokines has led to a modern conception of WAT as the largest endocrine organ. Therefore, it is conceivable that the dysfunction of WAT might be attributable to the pathophysiology of a variety of metabolic diseases. During the development of obesity, adipocytes become hypertrophic and can increase in size to 200mm in diameter, but the diffusion limit of oxygen is at most 100 mm. In this regard, hypertrophic adipocytes might endure hypoxia. Of note, hypoxia-inducible factor-1a (HIF-1a) and Glucose transporter 1(GLUT-1), which play a pivotal role in the response to hypoxia, are regarded as the master regulators of O2. Increasing evidence suggests that hypoxia in adipose tissue (AT) leads to chronic inflammation within the tissue, which subsequently results in the dysregulation of the production of inflammation-related adipokines, such as leptin, adiponectin, TNF-a, IL-6 and vascular endothelial growth factor (VEGF), which are viewed as central to the development of insulin resistance and metabolic syndrome.Objectives:1) To observe the influence of long-term ethanol consumption on Glucose Metabolism in rats.2) To observe the effect of long-term ethanol consumption on the body weight and visceral adipose tissue.3) To detect the influence of chronic ethanol on factor related to hypoxia in vitro and in vivo.4) To detect the influence of chronic ethanol consumption on inflammation-related adipokines in vitro and in vivo.Methods:1) Animal feedingTwenty-four wistar rats were randomly divided into control(C) and ethanol(E) (2.5g/Kg/d) groups according to their body weight after adaptive feeding for one week. An oral glucose tolerance test (OGTT) was carried out after 8 weeks. Blood samples and perirenal fat tissues were obtained.2) Cell cultureThe OP9 cells were seeded in a twelve-well plate and divided into three groups: controls(A); ethanol supplied during the differentiation(B); and ethanol supplied 10 d after differentiation was initiated(C). Adipocytes in group C were incubated in ethanol for 48 h later, all the medium and cells were obtained.3) Plasma glucose was measured using the glucose oxidases method. Insulin was measured by RIA. The homeostasis model assessment of insulin resistance(HOMA-IR) was calculated using the formula.4) Protein extraction and western blotting analysis was adopted to determine the protein such as HIF-la, GLUT1, TNF-a and IL-6 in both the WAT and OP9 cells. The leptin and VEGF in WAT were also measured.5) The concentration of TNF-a and IL-6 in serum and conditioned media was measured using mouse-specific ELISA kits.Results:1) Chronic heavy ethanol impaired glucose tolerance and insulin sensitivity.2) Chronic heavy ethanol feeding led to visceral adipose tissue accumulation although the body weights in both groups showed no significant differences.3) Chronic heavy ethanol increased the expression of factor related to hypoxia such as HIF-la and GLUT1 in both the WAT and OP9 cell.4) Chronic heavy ethanol increased the expression and secretion of inflammation-related adipokines such as TNF-a, IL-6, leptin and VEGF.Conclusions:Chronic heavy ethanol can the accumulation of visceral adipose tissue (VAT), hypertrophic adipocytes might endure hypoxia, then chronic low-grade inflammation happened. It might be the mechanism that how the ethanol affect glucose metabolism.Background:Epidemiological data showed that incidence of obesity and type 2 diabetes mellitus (T2DM) increase worldwide. Glucagon-like peptide-1 (GLP-1) analogues are widely used to treat T2DM, and the effect of blood glucose control was confirmed. Moreover the ability of GLP-1 analogues to augment weight loss and improve insulin resistance was observed. The function of GLP-1 was depended on the binding with the GLP-1 receptor.High fat diet can lead to obesity and along with abnormal glucose metabolism, impaired glucose tolerance and insulin resistance which can lead to metabolic syndrome. Traditionally, adipose tissue(AT) is an organ that only stores energy, but recent studies found that adipose tissue plays an important role in the glucose metabolism and lipid metabolism as it can synthesis and secrete adipocytokines. GLP-1 R is expressed in adipose tissue. It was reported that the expression of GLP-1 R was decreasing in the AT who suffered obesity and insulin resistant (IR), but there are still few researches to reveal the relationship between the glucose intolerance and GLP-1 R in the AT. Previous studies showed that ethanol affect glucose metabolism via adipose tissue, studied about the ethanol and GLP-1 R in AT cannot be found.Objectives:To observe the effect of moderate ethanol consumption on the glucose metabolism and the expression of GLP-1 R in adipose tissue on rats with different diet.Methods:48 Wistar rats were randomly divided into four group:control group; ethanol group(2.5g/Kg/d); high-fat diet group; both ethanol (2.5G/Kg/d) and high-fat diet group. Intraperitoneal glucose tolerance test was performed after 7 weeks. The epididymal and perirenal fat pads were rapidly removed and weighed for the calculation of the relative adipose tissue weight compared with body weight. Protein extraction and western blotting analysis was adopted to determine the protein GLP-1R in adipose tissue.Result:The weight gained more, visceral fat deposition and glucose intolerance were happened in the high fat diet group, while the expression of GLP-1R was reduced; moderate ethanol consumption did not affect the visceral fat content, glucose metabolism, and the expression of GLP-1R in adipose tissue while with a normal diet; but moderate ethanol consumption improved glucose intolerance induced by high fat diet via improved adipose tissue accumulation and the expression of GLP-1R in adipose tissue.Conclusion:Moderate ethanol improves glucose intolerance induced by high fat diet via increasing the GLP-1R in adipose tissue, but has no effect while with normal diet. |
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