Dietary Supplementation with Epigallocatechin Gallate Elevates Levels of Circulating Adiponectin in Non-Obese Type-2 Diabetic Goto-Kakizaki Rats

Epigallocatechin gallate (EGCG) reportedly enhances plasma adiponectin levels in models of insulin resistance and obesity. In this study, we found that EGCG increases plasma adiponectin levels and decreases plasma triacylglycerol levels in non-obese diabetic Goto-Kakizaki rats with insulin secretory dysfunction. These results suggest that EGCG ameliorates lipid metabolic abnormality even in non-obese rats, probably by increasing adiponectin production.     

Short-term pioglitazone treatment prevents free fatty acid-induced hepatic insulin resistance in normal rats: possible role of the resistin and adiponectin

We have evaluated the effects of a 2 week treatment with pioglitazone (Pio, 4mg/kg x d) on hepatic and peripheral insulin sensitivity, plasma adiponectin, and resistin concentrations in lipid-infused rats. Lipid infusion caused a large (60% in 4h) decrease in whole-body insulin sensitivity. Hepatic and peripheral insulin resistance contributed about equally to the whole-body insulin resistance. Pio treatment significantly improved whole-body insulin sensitivity due to normalization of hepatic insulin action, whereas peripheral insulin action remained unchanged and inhibited. Basal plasma resistin levels were approximately 4-fold lower in Pio-treated than in untreated rats. During lipid infusion, resistin levels rose in both Pio-treated and untreated rats, but remained significantly lower in Pio-treated than in untreated rats (P<0.01). Dot-blot analyses revealed a marked decrease in resistin protein levels in the liver of Pio-treated rats. Resistin levels were higher in muscle tissue in lipid group compared with control and Pio-treated rats (P<0.05). Fasting plasma adiponectin levels were 1.5-fold higher in Pio-treated than in untreated rats. We conclude that short-term treatment of rats with Pio prevented lipid-induced hepatic insulin resistance and that Pio mediated lowering of blood resistin and raising of adiponectin levels may have contributed to that effect.     

EGCG, a green tea polyphenol, improves endothelial function and insulin sensitivity, reduces blood pressure, and protects against myocardial I/R injury in SHR

Epigallocatechin gallate (EGCG), a bioactive polyphenol in green tea, may augment metabolic and vascular actions of insulin. Therefore, we investigated effects of EGCG treatment to simultaneously improve cardiovascular and metabolic function in spontaneously hypertensive rats (SHR; model of metabolic syndrome with hypertension, insulin resistance, and overweight). In acute studies, EGCG (1-100 microM) elicited dose-dependent vasodilation in mesenteric vascular beds (MVB) isolated from SHR ex vivo that was inhibitable by N(omega)-nitro-L-arginine methyl ester (L-NAME; nitric oxide synthase antagonist) or wortmannin [phosphatidylinositol (PI) 3-kinase inhibitor]. In chronic studies, 9-wk-old SHR were treated by gavage for 3 wk with EGCG (200 mg.kg(-1).day(-1)), enalapril (30 mg.kg(-1).day(-1)), or vehicle. A separate group of SHR receiving L-NAME (80 mg/l in drinking water) was treated for 3 wk with either EGCG or vehicle. Vasodilator actions of insulin were significantly improved in MVB from EGCG- or enalapril-treated SHR (when compared with vehicle-treated SHR). Both EGCG and enalapril therapy significantly lowered systolic blood pressure (SBP) in SHR. EGCG therapy of SHR significantly reduced infarct size and improved cardiac function in Langendorff-perfused hearts exposed to ischemia-reperfusion (I/R) injury. In SHR given L-NAME, beneficial effects of EGCG on SBP and I/R were not observed. Both enalapril and EGCG treatment of SHR improved insulin sensitivity and raised plasma adiponectin levels. We conclude that acute actions of EGCG to stimulate production of nitric oxide from endothelium using PI 3-kinase-dependent pathways may explain, in part, beneficial effects of EGCG therapy to simultaneously improve metabolic and cardiovascular pathophysiology in SHR. These findings may be relevant to understanding potential benefits of green tea consumption in patients with the metabolic syndrome.     

Circulating serum adiponectin concentrations do not differ between obese and non-obese caucasians and are unrelated to insulin sensitivity.

Reduced serum levels of adiponectin in obesity and insulin resistance seem paradoxical, since adipose tissue is the only source of adiponectin, and reports on that subject are contradictory. The aim of this study was to investigate the concentrations of adiponectin in non-obese and obese normoglycemic humans, and to determine the correlation between adiponectin and HOMA index of insulin sensitivity. Based on the WHO definition of obesity, 145 obese subjects and 49 non-obese controls (aged 20-55 years) were studied. The serum adiponectin concentrations did not differ between subjects and controls (p=0.6398) and were not correlated with HOMA index (r=-0.0211; p=0.8048, and r=-0.0523; p=0.4757, for subjects and controls, respectively). Adiponectin was not correlated with HOMA index in females (r=-0.0521; p=0.6546, and r=-0.0825; p=0.3981, for female subjects and controls, respectively) as well as in males (r=0.0033; p=0.9791, and r=0.0123; p=0.9131, for male subjects and controls, respectively). These results lead to the conclusion that neither the concentrations of adiponectin differ between obese and non-obese humans, nor does any relationship between adiponectin concentration and insulin sensitivity exist.     

运动对老年肥胖大鼠脂联素的影响

目的：探讨运动对老年肥胖大鼠内脏脂肪组织脂联素mRNA和蛋白质表达、血浆脂联素浓度及胰岛素抵抗的影响。方法：取雄性SD大鼠,鼠龄21 d,分青春期、壮年期和老年期三个阶段喂养高脂饲料（脂肪率为36.3%~40.0%）,建立老年肥胖模型。鼠龄达到60周后,取自然生长老年大鼠随机分为对照组（C）和老年运动组（AE）,n=6;取老年肥胖大鼠随机分为肥胖对照组（OC）和肥胖运动组（OE）,n=6。动物跑台坡度0°,运动速度及时间为（15 m/min×15 min）,4组/次,组间休息5 min,每次共运动60 min,5次/周,持续运动8周。8周后,检测内脏脂肪组织脂联素mRNA和蛋白质表达,测定血糖、血浆脂联素浓度和胰岛素浓度,计算胰岛素抵抗。结果：运动干预后,与对照组比较,肥胖对照组大鼠脂联素mRNA和蛋白质表达显著减低,血糖浓度和胰岛素抵抗明显增高;而老年运动组大鼠脂联素mRNA和蛋白质表达显著增高。与肥胖对照组大鼠比较,肥胖运动组大鼠脂联素mRNA和蛋白质表达显著增高、血浆脂联素水平增高,血糖浓度和胰岛素抵抗明显减低。结论：老年肥胖大鼠内脏脂肪组织脂联素mRNA和蛋白质表达均降低,伴随胰岛素抵抗、血糖升高。运动能显著增加其内脏脂肪组织脂联素mRNA和蛋白质表达,升高血浆脂联素水平,改善胰岛素抵抗,降低血糖。     

Dietary fish oil positively regulates plasma leptin and adiponectin levels in sucrose-fed, insulin-resistant rats

Insulin resistance and adiposity induced by a long-term sucrose-rich diet (SRD) in rats could be reversed by fish oil (FO). Regulation of plasma leptin and adiponectin levels, as well as their gene expression, by FO might be implicated in these findings. This study was designed to evaluate the long-term regulation of leptin and adiponectin by dietary FO in a dietary model of insulin resistance induced by long-term SRD in rats and to determine their impact on adiposity and insulin sensitivity. Rats were randomized to consume a control diet (CD; n = 25) or an SRD (n = 50) for 7 mo. Subsequently, the SRD-fed rats were randomized to consume SRD+FO or to continue on SRD for an additional 2 mo. Long-term SRD induced overweight and decreased both plasma leptin and adiponectin levels without change in gene expression. Dyslipidemia, adiposity, and insulin resistance accompanied these modifications. Shifting the source of fat to FO for 2 mo increased plasma levels of both adipokines, reversed insulin resistance and dyslipidemia, and improved adiposity. These results were not associated with modifications in gene expression. These results suggest that increasing both adipokines by dietary FO might play an essential role in the normalization of insulin resistance and adiposity in dietary-induced, insulin-resistant models.     

Glucocorticoids decrease serum adiponectin level and WAT adiponectin mRNA expression in rats

Objective

Accumulating evidence suggests that adiponectin plays an important role in the genesis of obesity and insulin resistance. Although it has been shown that glucocortocoids (GC) inhibit adiponectin expression in vitro, there exist discrepant results in vivo. In this study, we observe the effect of GC on the serum adiponectin level and adiponectin expression in white adipose tissue (WAT) in male SD rats.

Methods

An obese rat model was made by a high-fat diet. Both non-obese and obese rats were randomly divided into normal saline (intraperitoneal injection with normal saline 0.2 ml/100 g day for 20 days, NS), a low dose GC group (intraperitoneal injection with hydrocortisone sodium succinate 5 mg/kg day for 20 days, LDG) and a high dose GC group, respectively (intraperitoneal injection with hydrocortisone sodium succinate 15 mg/kg day for 20 days, HDG). Serum adiponectin levels were detected by ELISA and the adiponectin mRNA level was assayed by Northern blot.

Results

The serum adiponectin level significantly decreased after 80 days of the high-fat diet (P < 0.05), while it was not decreased after 80 days of the chow diet (P > 0.05). The serum adioponectin levels in both the non-obese and obese rats were significantly decreased after a 20-day GC injection period (P < 0.01). The adiponectin mRNA levels in epididymal fat after high dose GC injection, in both non-obese and obese rats were also decreased (P < 0.001).

Conclusions

A high-fat diet decreased serum adiponectin levels in the rat. GC decreased serum adiponectin levels, and this might be due to inhibited adiponectin mRNA expression in WAT. High-fat diet and GC have a synergistic effect on inhibiting adiponectin expression in rats.     

Caloric restriction increases adiponectin expression by adipose tissue and prevents the inhibitory effect of insulin on circulating adiponectin in rats

Aging is associated with redistribution of body fat and the development of insulin resistance. White adipose tissue emerges as an important organ in controlling life span. Caloric restriction (CR) delays the rate of aging possibly modulated partly by altering the amount and function of adipose tissue. Adiponectin is a major adipose-derived adipokine that has anti-inflammatory and insulin-sensitizing properties. This study examined the effects of CR on adiposity and gene expression of adiponectin, its receptors (AdipoR1 and AdipoR2) in adipose tissue and in isolated adipocytes of Brown Norway rats that had undergone CR for 4 months or fed ad libitum. The study also determined plasma concentrations of adiponectin and insulin in these animals and whether insulin infusion for 7 days affects adiponectin expression and its circulating concentrations under CR conditions. CR markedly reduced body weight as anticipated, epididymal fat mass and adipocyte size. CR led to an increase in plasma free fatty acid and glycerol (both twofold), and adipose triglyceride lipase messenger RNA (mRNA) in adipose tissue and isolated adipocytes (both >2-fold). Adiponectin mRNA levels were elevated in adipose tissue and adipocytes (both >2-fold) as was plasma adiponectin concentration (2.8-fold) in CR rats. However, CR did not alter tissue or cellular AdipoR1 and AdipoR2 expression. Seven days of insulin infusion decreased adiponectin mRNA in adipose tissue but did not reverse the CR-induced up-regulation of circulating adiponectin levels. Our results suggest that the benefits of CR could be, at least in part, dependent on enhanced expression and secretion of adiponectin by adipocytes.     

Increased insulin sensitivity in patients with anorexia nervosa: the role of adipocytokines

Anorexia nervosa (AN) is characterized by self-induced starvation leading to severe weight and fat loss. In the present study, we measured fasting plasma levels of adiponectin, leptin, resistin, insulin and glucose in 10 women with a restrictive type of AN and in 12 healthy women (C). Insulin sensitivity was determined according to homeostasis model assessment of insulin resistance (HOMA-R). Plasma resistin, leptin and insulin levels were significantly decreased, whereas plasma adiponectin levels were significantly increased in patients with AN compared to the C. HOMA-R was significantly decreased in patients with AN compared to the C group. Plasma adiponectin and leptin concentrations negatively and positively correlated with the body mass index and percentage body fat in both groups. Plasma adiponectin levels were negatively related to plasma insulin levels in the AN group only. In conclusion, we demonstrated that AN is associated with significantly decreased plasma leptin and resistin levels, markedly increased plasma adiponectin levels and increased insulin sensitivity. Plasma leptin and adiponectin levels were related to the body size and adiposity. Hyperadiponectinemia could play a role in increased insulin sensitivity of patients with AN. Neither body size and adiposity nor insulin sensitivity are the major determinants of plasma resistin levels in AN.     

Metabolic stress with a high carbohydrate diet increases adiponectin levels.

BACKGROUND: Adiponectin is an adipose tissue-specific protein, which possesses anti-atherogenic and antidiabetic properties, yet its plasma levels are decreased in subjects with metabolic syndrome. Although high fat diet has been linked to hypoadiponectinemia, the effect of high-carbohydrate diet on adiponectin levels is not known. Therefore, we studied the effect of high-carbohydrate diet on adiponectin levels in the rat models of hypertension and insulin resistance. METHODS: Rats were randomly assigned to the high carbohydrate diet [Sprague-Dawley rats with fructose enriched diet (SDR-F) and spontaneously hypertensive rats with sucrose enriched diet (SHR-S model)] or chow diet (Control group). Rats were followed for 6 weeks (SDR-F model) and 8 weeks (SHR-S model). Body weight, systolic blood pressure, plasma levels of glucose, insulin, triglycerides and adiponectin, were recorded. RESULTS: Both models were associated with features of the metabolic syndrome, namely, high insulin levels, increased blood pressure and triglyceride levels. Plasma adiponectin levels did not change in the control groups. In contrast, adiponectin levels increased by 39 and 30% compared to baseline following four and six weeks of fructose enriched diet in SDR (from 3.3+/-0.2 to 4.5+/-0.4 and 4.3+/-0.2 microg/ml, respectively, p<0.05). Likewise, five and eight weeks of sucrose enriched diet in SHR, induced a 54 and 81% increase in adiponectin levels compared to baseline (from 4.2+/-0.3 to 6.3+/-0.3 and 7.3+/-0.5 microg/ml, respectively, p<0.01). CONCLUSION: Metabolic stress with a high-carbohydrate diet increases plasma levels of adiponectin. Further studies will elucidate whether this is a transitory compensatory mechanism or a sign of target organ resistance to adiponectin.     

Effect of a High‐fat Diet on 24‐Hour Pattern of Circulating Adipocytokines in Rats

We have shown a significant disruption of 24‐h pattern of plasma pituitary, adrenal, and gonadal hormones in high‐fat‐fed rats. Our objective was to assess the effect of a high‐fat diet (35% fat) on mean levels and 24‐h pattern of several adipocytokines in rats. A normal diet–fed rats (4% fat) were used as controls. When body weight of high‐fat‐fed rats attained values about 25% higher than controls (after 66 days of treatment), the animals were killed at six different time intervals throughout a 24‐h cycle. Plasma concentrations of insulin, adiponectin, interleukin (IL)‐1, leptin, ghrelin, plasminogen activator inhibitor‐1 (PAI‐1), and monocyte chemoattractant protein‐1 (MCP‐1) were measured in a multianalyte profiling by using the Luminex‐100 system. Tumor necrosis factor α (TNFα) and IL‐6 were measured by enzyme‐linked immunosorbent assay. A significant hyperglycemia developed in high‐fat‐fed rats, together with a significant increase in plasma insulin. Mean levels of plasma adiponectin, IL‐1, IL‐6, TNFα, and leptin augmented, and ghrelin decreased, in high‐fat‐fed rats. The normal daily pattern of plasma insulin, adiponectin, IL‐1, IL‐6, TNFα, leptin, ghrelin, and MCP‐1 became disrupted in high‐fat‐fed rats. The results indicate that a high‐fat diet may bring about signs of insulin resistance and mild inflammation in rats, together with the disruption in daily variations of circulating insulin and ghrelin, and of several adipocytokines including leptin, adiponectin, IL‐1, IL‐6, TNFα, and MCP‐1.     

β-Conglycinin Lowers Very-Low-Density Lipoprotein-Triglyceride Levels by Increasing Adiponectin and Insulin Sensitivity in Rats

The relationship between insulin sensitivity and the plasma triglyceride-lowering effect induced by β-conglycinin was investigated. Male Wistar rats (19 weeks old) were fed diets containing casein, soy protein isolate, or β-conglycinin for 4 weeks. In oral glucose administration, the β-conglycinin-fed rats showed a significant decrease in the area under the glucose curve (0–60 min) as compared with the casein-fed rats. The hypoglycemic effect was significantly higher in the β-conglycinin-fed rats than in the casein-fed rats at 30 min after intraperitoneal insulin injection. The liver sterol regulatory element-binding-protein-1 mRNA expression level was significantly lower and the plasma adiponectin concentration was significantly higher in the β-conglycinin-fed rats than in the casein-fed rats. The hypotriglyceridemic effect of β-conglycinin depended on a significant decrease in the concentration of very-low-density-lipoprotein triglycerides. These results indicate that β-conglycinin increases adiponectin levels and improves glucose tolerance. The ability of β-conglycinin to lower plasma lipid levels might be due to increased insulin sensitivity of the liver.     

Hyperglycemia prevents the suppressive effect of hyperinsulinemia on plasma adiponectin levels in healthy humans

Adiponectin is a fat-derived hormone with insulin-sensitizing properties. In patients with type 2 diabetes plasma adiponectin levels are decreased. Since these patients are characterized by high plasma insulin and glucose concentrations, hyperinsulinemia and hyperglycemia could be responsible for the downregulation of adiponectin. Insulin decreases adiponectin levels in humans. The effect of hyperglycemia is unknown. To determine the selective effects of insulin, glucose, or their combination on plasma adiponectin, clamps were performed in six healthy males on four occasions in a crossover design: 1) lower insulinemic-euglycemic clamp (100 pmol/l insulin, 5 mmol/l glucose) (reference clamp); 2) hyperinsulinemic-euglycemic clamp (400 pmol/l insulin, 5 mmol/l glucose); 3) lower insulinemic-hyperglycemic clamp (100 pmol/l insulin, 12 mmol/l glucose); and 4) hyperinsulinemic-hyperglycemic clamp (400 pmol/l insulin, 12 mmol/l glucose). Adiponectin concentrations and high-molecular-weight (HMW)-to-total adiponectin ratio were measured at the start and end of the 6-h clamps. After the 6-h study period, total plasma adiponectin levels were significantly (P = 0.045) decreased by 0.63 microg/ml in the lower insulinemic-euglycemic clamp (clamp 1). In both euglycemic groups (clamps 1 and 2) adiponectin concentrations significantly declined (P = 0.016) over time by 0.56 microg/ml, whereas there was no change in both hyperglycemic groups (clamps 3 and 4) (P = 0.420). In none of the clamps did the ratio of HMW to total adiponectin change. We conclude that insulin suppresses plasma adiponectin levels already at a plasma insulin concentration of 100 pmol/l. Hyperglycemia prevents the suppressive effect of insulin. This suggests that, in contrast to glucose, insulin could be involved in the downregulation of plasma adiponectin in insulin-resistant patients.     

Insulin, leptin, and adiponectin receptors in colon: regulation relative to differing body adiposity independent of diet and in response to dimethylhydrazine

Obesity has recently become a focus of research to elucidate diet and lifestyle factors as important risk factors for colon cancer. Altered levels of insulin, leptin, and adiponectin have been identified as potential candidates increasing colon cancer risk within the prevailing obesogenic environment. There has been considerable research to characterize signaling via these hormones in the brain, liver, and adipose tissue; however, very little is known of their emerging role in peripheral signaling, particularly in epithelial tissues. This study profiles insulin, leptin, and adipokine receptors in the rat colon, revealing novel microanatomical location of these receptors and thereby supporting a potential role in regulating colonic tissue. Potential involvement of insulin, leptin, and adiponectin receptors in increased risk of colon cancer was investigated using Sprague-Dawley rats, either resistant or susceptible to diet-induced obesity. Regulation of insulin, leptin, and adiponectin receptors as a consequence of differing levels of adiposity was assessed regionally in the colon in response to treatment with the chemical carcinogen 1,2-dimethylhydrazine (DMH). However, significantly increased fat mass, increased levels of plasma insulin, leptin, and triglycerides, previously associated with an increased risk of colon cancer, were not associated with promotion of precancerous lesions in the experimental rats or deregulation of insulin, leptin, or adiponectin receptors. These findings do not support a direct link between the deregulation of insulin and adipokine levels observed in obese rats and an increased risk of colon carcinogenesis.     

A nonspecific phosphotyrosine phosphatase inhibitor, bis(maltolato)oxovanadium(IV), improves glucose tolerance and prevents diabetes in Zucker diabetic fatty rats

The molecular basis of insulin resistance, a major risk factor for development of Type II diabetes, involves defective insulin signaling. Insulin-mediated signal transduction is negatively regulated by the phosphotyrosine phosphatase, PTP1B, and numerous studies have demonstrated that organo-vanadium compounds, which are nonselective phosphotyrosine phosphatase inhibitors, have insulin-mimetic properties. However, whether or not vanadium compounds can prevent the transition from insulin resistance to overt diabetes is unknown. We compared the ability of bis(maltolato)oxovanadium(IV) (BMOV), an orally bioavailable organo-vanadium compound, and rosiglitazone maleate (RSG), a known insulin sensitizer, to prevent development of diabetes in Zucker diabetic fatty (ZDF) rats. Treatment began at 6 weeks of age when animals are insulin resistant and hyperinsulinemic, but not yet hyperglycemic, and ended at 12 weeks of age, which is 4 weeks after ZDF rats typically develop overt diabetes. BMOV-treated ZDF rats did not develop hyperglycemia, showed significant improvement in insulin sensitivity, and retained normal pancreatic islet morphology and endocrine cell distribution, similar to RSG-treated animals. BMOV and RSG treatment also prevented the hyper-phagia and polydipsia present in untreated ZDF rats; however, BMOV-treated ZDF rats gained much less weight than did RSG-treated animals. Circulating levels of adiponectin decreased in untreated ZDF rats compared to lean controls, but these levels remained normal in BMOV-treated ZDF rats. In contrast, in RSG-treated ZDF rats, plasma adiponectin levels were nearly 4-fold higher than in lean control rats, primarily as a result of a large increase in the amount of low-molecular weight forms of adiponectin in circulation. These data demonstrate that phosphatase inhibition offers a new approach to diabetes prevention, one that may have advantages over current approaches.     

脂肪组织特异表达的脂连蛋白（Adiponectin）及其球状区的克隆表达及体内活性的检测

3T3 L1脂肪细胞特异分泌一分子量约为 30kD的蛋白质 ,命名为ACRP30。ACRP30只在分化后的脂肪细胞中表达 ,在对胰岛素敏感度不一样的老鼠模型中 ,降低ACRP30的表达与胰岛素不敏感有关。为了研究人ACRP30同源基因 ,运用RT PCR方法分别克隆了脂连蛋白和球状区脂连蛋白 (脂连蛋白的C端球状区域 )基因 ,并在大肠杆菌中获得了融合表达。用融合球状区脂连蛋白蛋白免疫新西兰兔 ,得到了滴度为 1 0 0 0 0的多克隆抗体。用Western印迹方法检测到了人血液中一种能与该抗体作用的大小约为 38kD的蛋白质 ,此蛋白质也能被抗ACRP30的抗体检测到。单一注射融合脂连蛋白或者球状区脂连蛋白能显著降低糖尿病大鼠的血糖浓度 ,这些结果提示重组的脂连蛋白和球状区脂连蛋白具有生物学活性 ,为脂连蛋白的功能研究打下了一定的基础     

The counteracting effects of (-)-Epigallocatechin-3-Gallate on the immobilization stress-induced adverse reactions in rat pancreas

Many studies suggest that Epigallocatechin-3-Gallate (EGCG) has many protective effects. But little is known about its protective effects against chronic restraint stress-induced damage in rats. The aim was to demonstrate the potential protective effects of EGCG against harmful pancreatic damage to the immobilization stress in the rat model. Forty rats, 2 months old, were divided into four groups (n = 10): control group; EGCG group, rats received EGCG by gavage (100 mg/kg /day) for 30 days; stressed group, rats exposed to immobilization stress; and stressed with EGCG group, rats exposed to immobilization stress and received EGCG for 30 days. Glycemic status parameters, corticosterone, and inflammatory markers were investigated on the first day, 15th day, and the 30th day of the experiment. Pancreatic oxidative stress markers and cytokines were evaluated. Histological, immunohistological, and statistical studies were performed. On the 15th day, fasting blood glucose (FBG), fasting plasma insulin (FPI), homeostatic model assessment for insulin resistance (HOMA-IR), and fasting plasma corticosterone were significantly higher in the stressed group when compared with first and 30th day in the same group as well as when compared with control and stressed with EGCG groups. The stressed group revealed significantly higher pancreatic IL-1β, IL-6, TNF-α, MDA, and NO, serum amylase and serum lipase, and significantly lower GSH, SOD, and CAT when compared to control and stressed with EGCG groups. EGCG treatment attenuated the pancreatic stress-induced cellular degeneration, leucocytic infiltration, and cytoplasmic vacuolations; significantly decreased area percentage of collagen fibers; and significantly increased mean area percentage of insulin immunopositive cell as compared with stressed group. EGCG is a protective agent against immobilization stress because of its anti-diabetic, anti-inflammatory, and and anti-oxidative stress properties, as confirmed by biochemical and histological alterations.     

Regulation of adiponectin production by insulin: interactions with tumor necrosis factor-α and interleukin-6

Obesity is often associated with insulin resistance, low-grade systemic inflammation, and reduced plasma adiponectin. Inflammation is also increased in adipose tissue, but it is not clear whether the reductions of adiponectin levels are related to dysregulation of insulin activity and/or increased proinflammatory mediators. In this study, we investigated the interactions of insulin, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in the regulation of adiponectin production using in vivo and in vitro approaches. Plasma adiponectin and parameters of insulin resistance and inflammation were assessed in a cohort of lean and obese insulin-resistant subjects. In addition, the effect of insulin was examined in vivo using the hyperinsulinemic-euglycemic clamp, and in adipose tissue (AT) cultures. Compared with lean subjects, the levels of total adiponectin, and especially the high-molecular-weight (HMW) isomer, were abnormally low in obese insulin-resistant subjects. The hyperinsulinemic clamp data confirmed the insulin-resistant state in the obese patients and showed that insulin infusion significantly increased the plasma adiponectin in lean but not obese subjects (P < 0.01). Similarly, insulin increased total adiponectin release from AT explants of lean and not obese subjects. Moreover, expression and secretion of TNF-α and IL-6 increased significantly in AT of obese subjects and were negatively associated with expression and secretion of adiponectin. In 3T3-L1 and human adipocyte cultures, insulin strongly enhanced adiponectin expression (2-fold) and secretion (3-fold). TNF-α, and not IL-6, strongly opposed the stimulatory effects of insulin. Intriguingly, the inhibitory effect of TNF-α was especially directed toward the HMW isomer of adiponectin. In conclusion, these studies show that insulin upregulates adiponectin expression and release, and that TNF-α opposes the stimulatory effects of insulin. A combination of insulin resistance and increased TNF-α production could explain the decline of adiponectin levels and alterations of isomer composition in plasma of obese insulin-resistant subjects.     

Adiponectin inhibits spontaneous and catecholamine-induced lipolysis in human adipocytes of non-obese subjects through AMPK-dependent mechanisms

Adiponectin is an adipokine increasing glucose and fatty acid metabolism and improving insulin sensitivity. The aim of this study was to investigate the role of adiponectin in the regulation of adipocyte lipolysis. Human adipocytes isolated from biopsies obtained during surgical operations from 16 non-obese and 17 obese subjects were incubated with 1) human adiponectin (20 microg/ml) or 2) 0.5 mM AICAR - activator of AMPK (adenosine monophosphate activated protein kinase). Following these incubations, isoprenaline was added (10(-6) M) to investigate the influence of adiponectin and AICAR on catecholamine-induced lipolysis. Glycerol concentration was measured as lipolysis marker. We observed that adiponectin suppressed spontaneous lipolysis by 21 % and isoprenaline-induced lipolysis by 14 % in non-obese subjects. These effects were not detectable in obese individuals, but statistically significant differences in the effect of adiponectin between obese and non-obese were not revealed by two way ANOVA test. The inhibitory effect of AICAR and adiponectin on lipolysis was reversed by Compound C. Our results suggest, that adiponectin in physiological concentrations inhibits spontaneous as well as catecholamine-induced lipolysis. This effect might be lower in obese individuals and this regulation seems to involve AMPK.     

Plasma Adiponectin Levels in Overweight and Obese Asians

Objective: Hypoadiponectin has been documented in subjects with obesity, diabetes mellitus, or coronary heart disease, suggesting a potential use of plasma adiponectin in following the clinical progress in subjects with metabolic syndrome (MS). In this study, we investigated the plasma adiponectin levels in relation to the variables of MS among overweight/obese Asian subjects. Research Methods and Procedures: The plasma adiponectin, anthropometric and biochemical measurements, oral glucose tolerance tests (OGTT), and modified insulin suppression tests were performed on 180 overweight/obese Asian subjects [body mass index (BMI) ≥ 23 kg/m²], including 47 subjects with morbid obesity (BMI ≥ 40 kg/m²). Results: The plasma adiponectin levels negatively correlated with BMI, waist-to-hip ratio, fasting plasma glucose, insulin, triglyceride, uric acid levels, hyperinsulinemia, and glucose intolerance in OGTT, but positively with high-density lipoprotein-cholesterol. In contrast, they were not related to blood pressure and total cholesterol. Moreover, insulin sensitivity, measured by quantitative insulin sensitivity check index (QUICKI) or in insulin suppression tests, significantly correlated with the plasma adiponectin levels. Among morbidly obese subjects, only the waist-to-hip ratio correlated with the plasma adiponectin levels. Using multivariate linear regression models, the area under curve of plasma glucose in OGTT and high-density lipoprotein-cholesterol among the overweight/obese subjects and WHR among the morbidly obese subjects were significantly related to the plasma adiponectin levels after adjustment for other variables. Discussion: In overweight/obese Asians, the plasma adiponectin levels significantly correlated with various indices of MS except hypertension. Whether the plasma adiponectin level could be a suitable biomarker for following the clinical progress of MS warrants further investigation.