Increased fat accumulation in liver may link insulin resistance with subcutaneous abdominal adipocyte enlargement, visceral adiposity, and hypoadiponectinemia in obese individuals

BACKGROUND: Enlargement of adipocytes from subcutaneous abdominal adipose tissue (SAT), increased intrahepatic lipid content (IHL), intramyocellular lipid content (IMCL), and low circulating adiponectin concentrations are associated with insulin resistance. OBJECTIVE: Because adiponectin increases fat oxidation in skeletal muscle and liver, and the expression of the adiponectin gene in SAT is inversely associated with adipocyte size, we hypothesized that hypoadiponectinemia links hypertrophic obesity with insulin resistance via increased IMCL and IHL. DESIGN: Fifty-three obese Pima Indians with a mean (+/-SD) age of 27 +/- 8 y, body fat of 35 +/- 5%, and normal glucose regulation (normal fasting and 2-h glucose concentration per WHO 1999 criteria) underwent euglycemic-hyperinsulinemic clamp, biopsies of SAT and vastus lateralis muscle, and magnetic resonance imaging of the abdomen. RESULTS: Adipocyte diameter (AD) correlated positively with body fat (P < 0.0001) and IHL (estimated from magnetic resonance imaging intensity of liver; P = 0.047). No association was found between AD and plasma adiponectin or IMCL. Plasma adiponectin negatively correlated with type II IMCL (IIA, P = 0.004; IIX, P = 0.009) or IHL (P = 0.02). In a multivariate analysis, plasma adiponectin, AD, and visceral adipose tissue (VAT) independently predicted IHL. Low insulin-mediated glucose disposal was associated with low plasma adiponectin (P = 0.02) and high IHL (P = 0.0003), SAT (P = 0.02), and VAT (P = 0.04). High IHL was the only predictor of reduced insulin-mediated suppression of hepatic glucose production (P = 0.02) and the only independent predictor of insulin-mediated glucose disposal in a multivariate analysis. CONCLUSIONS: Increased lipid content in the liver may independently link hypoadiponectinemia, hypertrophic obesity, and increased visceral adiposity with peripheral and hepatic insulin resistance.     

内脂素与代谢综合征

与肥胖有关的2型糖尿病以及代谢综合征与机体脂肪组织的增加有显著关系.通过研究脂肪组织在代谢调节中所起的作用,可能会为治疗肥胖所致的胰岛素抵抗以及代谢综合征提供新的思路.内脂素是一种新发现的脂肪因子,它主要在内脏脂肪组织生成中发挥作用,并且具有类胰岛素活性的作用.现就内脂素与代谢相关疾病的联系及其对这些疾病的治疗前景作一综述.     

Splenic participation in glycemic homeostasis in obese and non-obese male rats

We evaluated the effects of splenectomy on glucose homeostasis in obese and non-obese rats. Obesity was induced by subcutaneous injections of monosodium glutamate (MSG; 4 g/kg) in neonatal rats. Control (non-obese) animals received equimolar saline. Splenectomy (SPL) was performed at 21 or 60 days of life (SPL₂₁ and SPL₆₀) in MSG obese and non-obese groups. Glucose tolerance, insulin resistance (IR), adiposity, histology of white adipose tissue (WAT) depots and glucose-induced insulin secretion (GIIS) in isolated pancreatic islets were evaluated at 90 days of life. In non-obese, despite of hyperphagia, the spleen ablation reduced body weight gain and energy efficiency, without changes in GIIS or IR. Slight reduction in glucose tolerance and augmented adipocyte size in subcutaneous WAT was noted in non-obese SPL₂₁ group. In MSG-SPL₂₁ rats was observed augmented body weight gain and energy efficiency, without alter adipocyte size. In contrast, MSG-SPL₆₀ rats had lower body weight gain, reduced energy efficiency and smaller adipocyte size in WAT visceral depot in relation to MSG non-operated. Spleen ablation reduced insulin plasma levels in the MSG-SPL₂₁ and MSG-SPL₆₀ groups. Moreover, splenectomy reduced GIIS and improved glucose tolerance in MSG-SPL₂₁ group. In MSG-SPL₆₀ rats were observed reduction in IR, without changes in GIIS, despite of elevated glucokinase expression in pancreatic islets. In conclusion, spleen ablation reduces body weight in non-obese rats and slightly modifies glucose homeostasis. In contrast, in MSG-induced obesity, absence of the spleen can ameliorate glucose tolerance and reduce insulin secretion, improving insulin sensitivity.     

血管生成素样蛋白与胰岛素抵抗和糖代谢的关系及在多囊卵巢综合征中的作用

多囊卵巢综合征(polycystic ovary syndrome,PCOS)是育龄期女性最常见的内分泌及代谢性疾病之一,PCOS患者发生心血管疾病和2型糖尿病的风险增加.越来越多的研究支持胰岛素抵抗(insulin resistance,IR)是PCOS重要的病理机制之一.血管生成素样蛋白(angiopoietin-...     

Metabolic adaptations to dexamethasone-induced insulin resistance in healthy volunteers

OBJECTIVE: Insulin resistance is observed in individuals with normal glucose tolerance. This indicates that increased insulin secretion can compensate for insulin resistance and that additional defects are involved in impaired glucose tolerance or type 2 diabetes. The objective of this study was to evaluate a procedure aimed at assessing the compensatory mechanisms to insulin resistance. RESEARCH METHODS AND PROCEDURES: Eight healthy nonobese female patients were studied on two occasions, before and after administration of 2 mg/d dexamethasone for 2 days during a two-step hyperglycemic clamp. Insulin secretion was assessed from plasma insulin concentrations. Insulin sensitivity was assessed from the ratio of whole-body glucose use (6,6 (2)H(2) glucose) to plasma insulin concentrations. This procedure is known to induce a reversible impairment of glucose tolerance and insulin resistance. RESULTS: In all subjects, dexamethasone induced a decrease in insulin sensitivity and a proportionate increase in first-phase insulin secretion and in insulin concentrations at both steps of glycemia. The resulting hyperinsulinemia allowed the restoration of normal whole-body glucose uptake and the suppression of plasma free fatty acids and triglycerides. In contrast, the suppression of endogenous glucose production was impaired after dexamethasone (p < 0.01). DISCUSSION: Increased insulin secretion fully compensates dexamethasone-induced insulin resistance in skeletal muscle and adipose tissue but not in the liver. This suggests that failure to overcome hepatic insulin resistance can impair glucose tolerance. The compensatory insulin secretion in response to insulin resistance can be assessed by means of a hyperglycemic clamp after a dexamethasone challenge.     

Black soybean extract reduces fatty acid contents in subcutaneous,but not in visceral adipose triglyceride in high-fat fed rats

Abstract

It is known that black soybean (BS) extract, rich in polyphenols, has beneficial effects against obesity, inflammation and insulin resistance. However, detailed effects of BS on lipid metabolism have not been documented well. In the present study, we compared fatty acid composition in visceral and subcutaneous adipose tissues of high-fat fed (HFF) rats and BS administered HFF rats. Black soybean administration for 6 weeks influenced neither body nor adipose tissue weights, blood glucose, plasma insulin levels, or insulin sensitivity. However, BS reduced several saturated (C14:0 and C16:0), monounsaturated (C14:1n-5 and C18:1n-9) and n-6 polyunsaturated (C18:2n-6, C20:3n-6, C20:4n-6 and C22:4n-6) fatty acid contents in subcutaneous fat without any change in n-3 polyunsaturated fatty acid contents. No such effect was observed in fatty acid composition in visceral fat. Long-chain fatty acids are involved in regulation of inflammation. Therefore, those reduced fatty acids may be linked to the effects on suppressing inflammation.     

Visceral obesity, metabolic syndrome, insulin resistance and cancer

This paper presents emerging evidence linking visceral adiposity and the metabolic syndrome (MetSyn) with carcinogenesis. The link between obesity and cancer has been clearly identified in a multitude of robust epidemiological studies. Research is now focusing on the role of visceral adipose tissue in carcinogenesis; as it is recognised as an important metabolic tissue that secretes factors that systemically alter the immunological, metabolic and endocrine milieu. Excess visceral adipose tissue gives rise to a state of chronic systemic inflammation with associated insulin resistance and dysmetabolism, collectively known as the MetSyn. Prospective cohort studies have shown associations between visceral adiposity, the MetSyn and increased risk of breast cancer, colorectal cancer and oesophageal adenocarcinoma. Furthermore, visceral adiposity and the MetSyn have been associated with increased tumour progression and reduced survival. The mechanisms by which visceral adiposity and the MetSyn are thought to promote tumorigenesis are manifold. These include alterations in adipokine secretion and cell signalling pathways. In addition, hyperinsulinaemia, subsequent insulin resistance and stimulation of the insulin-like growth factor-1 axis have all been linked with visceral adiposity and promote tumour progression. Furthermore, the abundance of inflammatory cells in visceral adipose tissue, including macrophages and T-cells, create systemic inflammation and a pro-tumorigenic environment. It is clear from current research that excess visceral adiposity and associated dysmetabolism play a central role in the pathogenesis of certain cancer types. Further research is required to elucidate the exact mechanisms at play and identify potential targets for intervention.     

Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation in adipose tissue

High-fat diet-induced obesity is associated with a chronic state of low-grade inflammation, which pre-disposes to insulin resistance (IR), which can subsequently lead to type 2 diabetes mellitus. Macrophages represent a heterogeneous population of cells that are instrumental in initiating the innate immune response. Recent studies have shown that macrophages are key mediators of obesity-induced IR, with a progressive infiltration of macrophages into obese adipose tissue. These adipose tissue macrophages are referred to as classically activated (M1) macrophages. They release cytokines such as IL-1β, IL-6 and TNFα creating a pro-inflammatory environment that blocks adipocyte insulin action, contributing to the development of IR and type 2 diabetes mellitus. In lean individuals macrophages are in an alternatively activated (M2) state. M2 macrophages are involved in wound healing and immunoregulation. Wound-healing macrophages play a major role in tissue repair and homoeostasis, while immunoregulatory macrophages produce IL-10, an anti-inflammatory cytokine, which may protect against inflammation. The functional role of T-cell accumulation has recently been characterised in adipose tissue. Cytotoxic T-cells are effector T-cells and have been implicated in macrophage differentiation, activation and migration. Infiltration of cytotoxic T-cells into obese adipose tissue is thought to precede macrophage accumulation. T-cell-derived cytokines such as interferon γ promote the recruitment and activation of M1 macrophages augmenting adipose tissue inflammation and IR. Manipulating adipose tissue macrophages/T-cell activity and accumulation in vivo through dietary fat modification may attenuate adipose tissue inflammation, representing a therapeutic target for ameliorating obesity-induced IR.     

Effects of food pattern change and physical exercise on cafeteria diet-induced obesity in female rats

Obesity affects a large number of people around the world and appears to be the result of changes in food intake, eating habits and physical activity levels. Changes in dietary patterns and physical exercise are therefore strongly recommended to treat obesity and its complications. The present study tested the hypothesis that obesity and metabolic changes produced by a cafeteria diet can be prevented with dietary changes and/or physical exercise. A total of fifty-six female Wistar rats underwent one of five treatments: chow diet; cafeteria diet; cafeteria diet followed by a chow diet; cafeteria diet plus exercise; cafeteria diet followed by a chow diet plus exercise. The duration of the experiment was 34 weeks. The cafeteria diet resulted in higher energy intake, weight gain, increased visceral adipose tissue and liver weight, and insulin resistance. The cafeteria diet followed by the chow diet resulted in energy intake, body weight, visceral adipose tissue and liver weight and insulin sensitivity equal to that of the controls. Exercise increased total energy intake at week 34, but produced no changes in the animals' body weight or adipose tissue mass. However, insulin sensitivity in animals subjected to exercise and the diet was similar to that of the controls. The present study found that exposure to palatable food caused obesity and insulin resistance and a diet change was sufficient to prevent cafeteria diet-induced obesity and to maintain insulin sensitivity at normal levels. In addition, exercise resulted in normal insulin sensitivity in obese rats. These results may help to develop new approaches for the treatment of obesity and type 2 diabetes mellitus.     

西布曲明对肥胖小鼠葡萄糖代谢的影响

目的:探讨西布曲明干预对高脂饮食诱导肥胖ICR小鼠葡萄糖代谢的影响。方法:高脂饲料喂养雄性ICR小鼠8周,建立肥胖小鼠模型。西布曲明(7 mg.kg-1.day-1)灌胃干预8周。然后行腹腔注射葡萄糖耐量试验(IPGTT)、胰岛素耐量试验(ITT)及microPET显像;测量小鼠的体重、脂肪组织重量及血生化指标;实时荧光定量RT-PCR方法检测肌肉组织中糖代谢相关基因的相对表达量。结果:西布曲明干预组小鼠体重显著减轻(P<0.05),皮下脂肪、内脏脂肪重量显著降低(P值均小于0.01),空腹血糖显著降低(P<0.05)。ITT试验中,西布曲明干预组小鼠各时间点血糖均低于对照组,差异在90分钟时有显著性(P<0.05);血糖的曲线下面积也显著低于对照组(P<0.05)。另外,西布曲明干预组小鼠的棕色脂肪摄取葡萄糖增多(P<0.05),但肌肉组织内糖代谢相关基因GLUT4、GYS1、HK2、PGC1、IRS1和MSTN的表达量没有显著改变。结论:西布曲明可以减轻小鼠体重,减少白色脂肪重量,增加棕色脂肪代谢能力并在一定程度上改善肥胖小鼠的胰岛素敏感性;西布曲明改善肥胖小鼠葡萄糖代谢的作用可能与肌肉组织中的GLUT4、GYS1、HK2、PGC1、IRS1和MSTN的表达水平无关。     

慢性酒精摄入对大鼠脂肪组织胰岛素敏感性影响

目的观察不同剂量酒精对雄性大鼠脂肪组织胰岛素敏感性的影响,并研究其可能的分子机制。方法用不同浓度(v/v)的酒精灌胃19 w,检测大鼠血清中胰岛素、葡萄糖含量,计算胰岛素抵抗程度;采用RT-PCR检测脂肪组织中磷脂酰肌醇-3-磷酸激酶(PI3K)mRNA、葡萄糖转运体4(GLUT4)mRNA表达水平。结果与对照组相比,中、高剂量组空腹葡萄糖浓度升高有统计学意义(P<0.05),低、中剂量组胰岛素浓度升高有统计学意义(P<0.05);各剂量组胰岛素抵抗指数(HOMA-IR)的升高均有统计学意义(P<0.05)。各剂量组的PI3K mRNA和GLUT4 mRNA表达均升高。结论长期过量酒精摄入引起胰岛素抵抗,引起脂肪组织胰岛素信号转导途径中磷PI3K mRNA和GLUT4 mRNA的表达升高。     

Inflammation markers are modulated by responses to diets differing in postprandial insulin responses in individuals with the metabolic syndrome

BACKGROUND: Inflammation may be a mechanism by which high postprandial insulin and glucose responses increase the risk of type 2 diabetes mellitus. OBJECTIVE: We hypothesized that dietary carbohydrates characterized by different postprandial insulin responses may differentially modify cytokine concentrations in plasma and gene expression in subcutaneous adipose tissue. DESIGN: Individuals (n = 47) with the metabolic syndrome were randomly assigned to a 12-wk diet with oat and wheat bread and potato (high postprandial insulin response) or rye bread and pasta (low postprandial insulin response). Postprandial glucose and insulin responses to the oat and wheat bread meal and to the rye bread meal were determined in 19 individuals before intervention. RESULTS: During the 12-wk diet, the change in the gene expression of interleukin (IL)-10 receptor alpha and tumor necrosis factor-alpha in subcutaneous adipose tissue differed between the groups (P = 0.002 and P = 0.083, respectively). Moreover, the change in fasting plasma concentrations of IL-1beta and IL-6 differed between the groups (P = 0.020 and P = 0.055, respectively). In the postprandial challenge, the insulin response to the rye bread meal was lower than that to the oat and wheat bread meal (P < 0.001), whereas there were no differences in the mean blood glucose response. In contrast, plasma glucose concentrations decreased more below fasting concentrations 2.5-3 h after the oat and wheat bread meal than after the rye bread meal. A late postprandial rebound of free fatty acids was detected after the oat and wheat bread meal (P = 0.048). CONCLUSIONS: Long-term intake of cereal foods with differing postprandial insulin responses may be a factor that modulates the inflammatory status in individuals with the metabolic syndrome.     

Dietary glucose increases plasma insulin and decreases brown adipose tissue thermogenic activity in adrenalectomized ob/ob mice

The purpose of this study was to determine whether consumption of a high glucose diet would increase plasma insulin concentrations and decrease brown adipose tissue metabolism in adrenalectomized ob/ob mice previously fed a high starch diet. Male sham-operated and adrenalectomized ob/ob and lean mice were fed a high starch diet for 12 d, then switched to a high glucose diet for the last 2 or 4 d of the 14- or 16-d feeding trials. Adrenalectomized ob/ob mice consumed 16% more energy and gained 50% more weight without an increase in oxygen consumption when switched from a high starch diet to a high glucose diet. Within 2 d after the switch to the high glucose diet, plasma insulin concentrations increased by 70% without any change in plasma glucose concentrations; brown adipose tissue metabolism, as assessed by GDP binding to brown adipose tissue mitochondria, was decreased by 26% 4 d after the diet switch. Sham-operated ob/ob and lean mice and adrenalectomized lean mice were minimally affected by the switch to the high glucose diet. The increase in plasma insulin concentrations in adrenalectomized ob/ob mice induced by the high glucose diet may contribute to the observed depression in brown adipose tissue metabolism.     

No evidence of insulin resistance in normal weight vegetarians

Summary Background Diets rich in carbohydrates with a low glycemic index and with high fiber content are associated with flat post–prandial rises of blood glucose, minimal post-prandial insulin secretion and maintenance of insulin sensitivity. Protective food commodities in the prevention of cardiovascular disease, insulin resistance syndrome or diabetes are crucial components of the vegetarian diet. Aim of the study Insulin resistance values were assessed in relation to different nutrition. Metabolic abnormality is a predictor of age–related diseases and can be more pronounced in obese subjects. Insulin resistance values in normal weight subjects of two different nutritional habits were correlated with age. Methods Fasting concentrations of glucose and insulin as well as calculated values of insulin resistance IR (HOMA) were assessed in two nutritional groups of apparently healthy adult subjects (age range 19 – 64 years) with normal weight (body mass index 18.6 – 25.0 kg/m²): a vegetarian group (95 long–term lacto–ovo–vegetarians; duration of vegetarianism 10.2 ± 0.5 years) and a non-vegetarian control group (107 subjects of general population on traditional western diet). Intake of energy and main nutrients (fats, saccharides, proteins) was similar in both groups. Results Glucose and insulin concentrations and IR (HOMA) values were significantly lower in vegetarians (glucose 4.47 ± 0.05 vs. 4.71 ± 0.07 mmol/l; insulin 4.96 ± 0.23 vs. 7.32 ± 0.41 mU/l; IR (HOMA) 0.99 ± 0.05 vs. 1.59 ± 0.10). IR (HOMA) dependence on age was only significant in subjects on a western diet. A significant increase of IR was found already in the age range 31–40 years, compared to vegetarians and it continued in later age decades. Age independent and low insulin resistance values in vegetarians are a consequence of an effective diet prevention by long–term frequent consumption of protective food. Vegetarians had a significantly higher consumption of whole grain products, pulses, products from oat and barley. Conclusion The results of age independent and low values of insulin resistance document abeneficial effect of long–term vegetarian nutrition in prevention of metabolic syndrome, diabetes and cardiovascular disease.     

Coplanar Polychlorinated Biphenyls Impair Glucose Homeostasis in Lean C57BL/6 Mice and Mitigate Beneficial Effects of Weight Loss on Glucose Homeostasis in Obese Mice

Background: Previous studies demonstrated that coplanar polychlorinated biphenyls (PCBs) promote proinflammatory gene expression in adipocytes. PCBs are highly lipophilic and accumulate in adipose tissue, a site of insulin resistance in persons with type 2 diabetes.Objectives: We investigated the in vitro and in vivo effects of coplanar PCBs on adipose expression of tumor necrosis factor α (TNF-α) and on glucose and insulin homeostasis in lean and obese mice.Methods: We quantified glucose and insulin tolerance, as well as TNF-α levels, in liver, muscle, and adipose tissue of male C57BL/6 mice administered vehicle, PCB-77, or PCB-126 and fed a low fat (LF) diet. Another group of mice administered vehicle or PCB-77 were fed a high fat (HF) diet for 12 weeks; the diet was then switched from HF to LF for 4 weeks to induce weight loss. We quantified glucose and insulin tolerance and adipose TNF-α expression in these mice. In addition, we used in vitro and in vivo studies to quantify aryl hydrocarbon receptor (AhR)-dependent effects of PCB-77 on parameters of glucose homeostasis.Results: Treatment with coplanar PCBs resulted in sustained impairment of glucose and insulin tolerance in mice fed the LF diet. In PCB-77–treated mice, TNF-α expression was increased in adipose tissue but not in liver or muscle. PCB-77 levels were strikingly higher in adipose tissue than in liver or serum. Antagonism of AhR abolished both in vitro and in vivo effects of PCB-77. In obese mice, PCB-77 had no effect on glucose homeostasis, but glucose homeostasis was impaired after weight loss.Conclusions: Coplanar PCBs impaired glucose homeostasis in lean mice and in obese mice following weight loss. Adipose-specific elevations in TNF-α expression by PCBs may contribute to impaired glucose homeostasis.     

Adiponectin: Novelties in Metabolism and Hormonal Regulation

Abstract

Adiponectin is a protein secreted exclusively by white adipose tissues and is abundantly present in human plasma. Adiponectin was found decreased in obese and diabetes mellitus type 2 patients and increased with weight reduction. A negative correlation between circulating adiponectin levels and body mass index and insulin resistance has been demonstrated. Plasma adiponectin concentrations were found lower in diabetes mellitus type 2 patients with coronary artery disease. Moreover, studies in aortic endothelial cells revealed that the protein exerts a dose-dependent decrease of the surface expression of vascular adhesion molecules and cytokine production from macrophages, suggesting the implication of adiponectin in atherosclerosis and inflammation. Weight loss and treatment with thiazolidinediones stimulate endogenous adiponectin production. Peripheral administration of adiponectin leads to reduction of visceral adiposity and increase of free fatty acid oxidation and insulin resistance. Furthermore, it enhances the expression of uncoupling proteins and sympathetic nerve activity in adipose tissues. Experimental studies in mice have shown that intraperitoneal administration of adiponectin lowers plasma glucose. These data show adiponectin to be an important factor in the issue of obesity and its associated disorders, and indicate a potential future utilization of adiponectin as a drug in the treatment of metabolic syndrome.     

共轭亚油酸与运动对青春期肥胖大鼠肝脏及脂肪组织视黄醇结合蛋白4的影响

目的探讨共轭亚油酸(CLA)与运动对青春期肥胖大鼠肝脏及脂肪组织视黄醇结合蛋白4(RBP4)的影响。方法选取喂饲普通饲料的青春期SD大鼠8只为空白对照组(C),高脂组建模7周选取32只肥胖鼠随机分为4组,每组8只,分别为安静对照组(OC)、安静补CLA组(OCC)、运动组(OM)、运动结合CLA组(OMC)。动物跑台跑速为21~25 m/min,60 min/次;CLA灌胃1.6 g/kg,1次/日,5次/周,连续8周。实验结束后麻醉动物,采集血液及组织,测血糖、计算胰岛素敏感性,检测内脏脂肪组织RBP4 mRNA表达、肝脏组织RBP4蛋白表达及血浆RBP4浓度。结果干预后OM、OMC组体重、体重增长幅度和体脂百分比、血糖、内脏脂肪组织RBP4mRNA表达、肝脏组织RBP4蛋白表达、血浆RBP4浓度低于OC、OCC组(P<0.01)。OM、OMC组胰岛素敏感性高于OC、OCC组(P<0.01)。OMC组体重、体重增长幅度、胰岛素敏感性高于OM组,体脂百分比、血糖、RBP4表达低于OM组,但差异无统计学意义。结论单纯运动与运动结合CLA显著降低青春期肥胖大鼠的体重、体重增长幅度、体脂百分比、血糖,提高胰岛素敏感性及降低内脏脂肪组织RBP4的mRNA表达、肝脏组织RBP4蛋白表达、血浆RBP4水平,运动与运动结合CLA效果明显优于单纯补CLA。     

CHRONIC ETHANOL CONSUMPTION AMELIORATES THE MATURITY-ONSET DIABETES-OBESITY SYNDROME IN CBA MICE

The effects of a chronic ethanol drinking schedule (20% solutionfor 6 weeks) on energy balance and carbohydrate and lipid metabolismhave been investigated in lean (32–36 g) and obesediabetic(40–44 g) CBA/Ca mice. The untreated obesediabetic miceexhibited hyperglycaemia, hypertriglyceridaemia, hyper-insulinaemiaand insulin resistance. The chronic ethanol treatment, whichyielded plasma ethanol levels of between 1 and 11 mM, loweredthe blood glucose, plasma insulin and tnacylglycerol levelstowards normal in the obese mice, but did not affect these parametersin the lean mice. The body weight of the obese mice tended toreturn to normal during the 6-week drinking period, althoughtheir total energy intake (9.2–10.0 kJ/g/week, food plusethanol-denved calories) was almost double that of the leanmice (4.8–5.4 kJ/g/week). The blood glucose response toacute insulin injection, which was significantly reduced inthe obese mice, became indistinguishable from the response ofnormal mice after chronic ethanol treatment. Soleus muscle glycogensynthesis in both lean and obese mice was not significantlyaltered by ethanol drinking, but brown adipose tissue lipogenesiswas significantly increased (by 50%) in the obese mice. It isproposed that ethanol is acting chronically to restore insulinsensitivity in the obese diabetic mice at doses which have littleor no effect in normal lean animals. This action is exerted,at least in part, at the level of brown adipose tissue lipogenesis.     

Extract from Dioscorea batatas ameliorates insulin resistance in mice fed a high-fat diet

The aim of this study was to investigate whether Dioscorea batatas (DB) extract attenuates high-fat diet (HFD)-induced insulin resistance in the visceral adipose tissues of mice, and by what mechanism(s). Mice were fed a HFD for 4 weeks to induce the early development of insulin resistance. The DB extract was administered to mice fed a HFD by oral gavage at a dose of 100?mg/kg body weight daily for 7 weeks. Biochemical parameters in blood were measured using enzymatic kits, and the expression levels of glucose transporter 4 (GLUT4), phosphorylated (p-)S6K1, phosphorylated v-akt murine thymoma viral oncogene homolog (p-AKT), and phosphorylated extracellular regulated kinase (p-ERK) in epididymal fat tissue were determined by western blot analyses. The DB extract effectively reversed the HFD-induced elevations in plasma glucose and insulin levels, and the homeostasis model assessment for insulin resistance and oral glucose tolerance test values. The level of p-AKT protein was up-regulated, whereas the levels of p-ERK and p-S6K1 proteins were down-regulated in the adipose tissues of DB mice compared with HFD mice. Furthermore, the DB extract significantly reversed the HFD-induced decrease in the plasma membrane GLUT4 level in the adipose tissue of mice. The DB extract improved glucose metabolism in HFD-fed mice through the up-regulation of plasma membrane GLUT4 content in the visceral adipose tissue. Activation of the insulin signaling cascade leading to GLUT4 translocation was the mechanism underlying the beneficial effects of the DB extract on early-stage obesity-induced insulin resistance.     

Adiponectin: novelties in metabolism and hormonal regulation

Adiponectin is a protein secreted exclusively by white adipose tissues and is abundantly present in human plasma. Adiponectin was found decreased in obese and diabetes mellitus type 2 patients and increased with weight reduction. A negative correlation between circulating adiponectin levels and body mass index and insulin resistance has been demonstrated. Plasma adiponectin concentrations were found lower in diabetes mellitus type 2 patients with coronary artery disease. Moreover, studies in aortic endothelial cells revealed that the protein exerts a dose-dependent decrease of the surface expression of vascular adhesion molecules and cytokine production from macrophages, suggesting the implication of adiponectin in atherosclerosis and inflammation. Weight loss and treatment with thiazolidinediones stimulate endogenous adiponectin production. Peripheral administration of adiponectin leads to reduction of visceral adiposity and increase of free fatty acid oxidation and insulin resistance. Furthermore, it enhances the expression of uncoupling proteins and sympathetic nerve activity in adipose tissues. Experimental studies in mice have shown that intraperitoneal administration of adiponectin lowers plasma glucose. These data show adiponectin to be an important factor in the issue of obesity and its associated disorders, and indicate a potential future utilization of adiponectin as a drug in the treatment of metabolic syndrome.