Adipose Tissue Adiponectin Levels Research Articles

Inflammation Markers in Adipose Tissue and Cardiovascular Risk Reduction by Pomegranate Juice in Obesity Induced by a Hypercaloric Diet in Wistar Rats.

Pomegranate juice (Punica granatum) has been used since ancient times in traditional medicine (Unani Medicine, Ayurveda); its main compounds are anthocyanins and ellagic acid, which have anti-inflammatory, antioxidant, hepatoprotective, and cardiovascular health effects. The objective was to evaluate the effect of pomegranate juice on inflammation, blood pressure, and vascular and physiological markers associated with obesity induced by a high-fat diet in a murine model. The results show that pomegranate juice reduces the concentration of low-density lipoprotein cholesterol (cLDL) 39% and increases the concentration of high-density lipoprotein cholesterol (cHDL) by 27%, leading to a 12%–18% decrease in the risk of cardiovascular diseases (CVD). In addition to reducing blood pressure by 24%, it also had an antiatherogenic effect by decreasing sE-selectin levels by 42%. On the other hand, the juice significantly increased adiponectin levels in adipose tissue, decreased levels of inflammation markers (tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor-1 (PAI-1), interleukin-17A (IL-17A), interleukin-6 (IL-6), interleukin-1β (IL-1β)), and inhibited the monocyte chemoattractant protein-1 (MCP-1). Pomegranate juice requires clinical studies to prove its immunoregulatory and therapeutic effects on cardiovascular and atherogenic risks.

The Effect of Vitamin D Administration on Leptin, Adiponectin and mRNA MCP-1 Levels in Adipose Tissue of Obese Female Wistar Rats

In obesity, there is an accumulation of adipocytes which produces adipokine that are pro-inflammatory substance, such as leptin and MCP-1 and anti-inflammatory substance, such as adiponectin, while the bioavailability of vitamin D is decreased. This research aimed to study the effect of vitamin D administration on leptin, MCP-1, and adiponectin levels in adipose tissue rats with obesity. Vitamin D was administered to the obese model of 6-9 months old female Wistar rats. This experiment was a randomized control group design with a post-test group design only. Twenty-seven (27) female obese Wistar rats were included in this study. The animals were divided randomly into 3 groups: 9 rats were given 2400 IU vitamin D (group A), 9 rats were given 800 IU vitamin D (group B) and 9 rats were given a placebo as control (group C). The administration of Vitamin D was given once daily for 8 weeks. The visceral adipose tissue was taken to measure the level of leptin, adiponectin and mRNA MCP-1. Data among groups was analyzed by using one-way ANOVA and followed by LSD test, at a significance level of p <0.05. The lowest level of leptin (1059.15+135.20 pg/ml) and mRNA MCP-1 (2.36 + 0.75 fg/ml) and the highest adiponectin level (3.43 + 0.47 ng/ml) were found in group A. In conclusion, oral administration of vitamin D (2400 IU) decreased pro-inflammatory substances, such as leptin and mRNA MCP-1 and increased anti-inflammatory substances, such as adiponectin, in visceral adipose tissue of obese female Wistar rats.

Continuous and Discontinuous Adherence to the Sticky Japanese Diet on Adiponectin and Leptin Regulation

Background: In order to evaluate the regulational role of adiponectin and leptin on obesity, we examined the significance of daily adherence to the Sticky Japanese Diet (SJD) on the preventions of obesity and metabolic syndrome by assessing the fat adiponectin/leptin and plasma leptin levels using normal and high-fat diet (HFD) mice. Methods: Five-week-old male ICR strain mice were placed in individual cages and randomly divided into eight groups based on feeding of SJD or not. At the end of each treatment period, plasma triglyceride, cholesterol, and leptin levels were measured by biochemical analysis. The adiponectin and leptin levels in adipose tissue were measured using RT-PCR. Results: In normal mice, an eight-week treatment of SJD increased adiponectin levels in adipose tissue. However, four weeks after discontinuing the SJD, these levels decreased. Furthermore, continuous feeding of the SJD for eight weeks increased plasma leptin levels but not that of adipose tissue. And then, discontinuing the SJD for more than eight days resulted in a decrease in plasma leptin levels. In HFD mice, an increase in body weight and visceral fat was seen at eight days after discontinuing the SJD which was undertaken for a total of eight weeks. At this time, the plasma leptin levels in these mice were substantially higher than in normal mice, although these levels were getting to be decreased over four weeks. Conclusion: This study revealed that discontinuous adherence to the SJD induced decreases in both adiponectin and leptin levels. Together with our previous publication, this paper suggests that daily adherence to the SJD might be essential for maintaining good health. Keywords: NuruNeba (Sticky Japanese Diet); Washoku (Japanese foods); normal diet; high-fat diet; leptin; adiponectin; obesity; mice Abbreviations: SJD: Sticky Japanese Diet; HFD: High-Fat Diet; CE-2: CLEA Rodent Diet CE-2; TG: Triglyceride; UCP1: Uncoupling Protein-1; BAT: Brown Adipose Tissue

Lipidomic analysis reveals therapeutic effects of Yijin-Tang on high-fat/high-cholesterol diet-induced obese mice

BackgroundIn Traditional Korean and Chinese medicine, the herbal remedy Yijin (Erchen)-Tang (YJT) is widely used to treat obesity-related disorders, and its therapeutic potential has been demonstrated in numerous studies. However, the systemic effect of YJT on obesity status and change of lipid metabolism by YJT still remains unknown. PurposeThis study aimed to investigate the therapeutic mechanism of the YJT on obesity by using lipidomics. MethodsTo evaluate the effects of treatment with YJT on obesity, C57BL/6 J mice were fed a high-fat and high-cholesterol (HFHC, 40% fat and 1% cholesterol) diet for 8 weeks and treated them with YJT for an additional 6 weeks. We then performed untargeted lipidomic analysis using ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry mass spectroscopy coupled with multivariate statistical analysis. ResultsYJT ameliorated obesity induced systemic inflammation and improved insulin resistance. Additionally, YJT protected against HFHC-diet-induced hepatic inflammation. To explore specific changes in lipid metabolism associated with the therapeutic effects of YJT, we performed untargeted lipid profiling of the plasma. Partial least squares-discriminant analysis (PLS-DA) score plots showed that YJT altered the lipid metabolic pattern of HFHC mice. In particular, ceramides and triglycerides with saturated fatty acids and monounsaturated fatty acids were significantly changed by YJT, which were significantly associated with insulin resistance, the AGE-RAGE signaling pathway in diabetic complications and adipocytokine signaling pathway in pathway enrichment analysis. Thus, we analyzed the changes in adipocytes and adipokine caused by YJT, and confirmed that YJT alleviated adipocytes inflammation and macrophage infiltration, and reversed HFHC-induced alterations in leptin and adiponectin levels in adipose tissue and plasma. ConclusionThese data suggest that YJT ameliorates obesity-induced systemic inflammation and insulin resistance by regulating lipid metabolism, and demonstrated that lipidomic profiling is a useful method to investigate the therapeutic effects of herbal decoctions in traditional Korean and Chinese medicine.

The effect of thyroid dysfunction and treatment on fat tissue adiponectin levels in rats

Adipose tissue is a hormonal active system that produces and releases leptin, adiponectin and resistin. Seen from this aspect, it may be thought that adiponectin may interact with the thyroid axis. Thyroid function disturbance led to changes on the body weight, muscle volume and adipose tissue. Experimental findings show that adiponectin and thyroid hormones have biological interactin with each other. However, various results have been reported a relationship between thyroid hormones and adiponection levels. The aim of the present study was to determine adipose tissue adiponectin levels in rats with thyroid dysfunction and after treatment. Study was performed on 40 Sprague-Dawley male rats. Groups were designed as 1-control, 2-hypothyroidism (Hypo), 3- hypothyroidism + Thyroxine, 4-hyperthyroidism (Hyper), 5-hyperthyroidism + PTU. At the end of 3 weeks experimental period, adipose tissues of rats were analyed for adiponection by Elisa. Experimental hypothyroidism reduced adipose tissue adiponectin levels, but hyperthyrodism increased. Treatment of hypothyroidism and hyperthyroidism corrected disrupted adiponectin levels to control. The results of the present study show that experimental thyroid dysfunction has affected adipose tissue adiponection levels in rats.

Gene expression levels of Casein kinase 1 (CK1) isoforms are correlated to adiponectin levels in adipose tissue and site-specific phosphorylation mediated by CK1 influences multimerization of adiponectin

Adiponectin, an adipocytokine with anti-inflammatory, antidiabetic, anti-atherogenic, and anti-cancer features, is mainly secreted by adipose tissue. Human adiponectin has an N-terminal collagenous domain and a C-terminal globular domain and builds characteristic homomeres including trimers, hexamers and high molecular weight (HMW) 12 – 18-mers. The beneficial effects of adiponectin in humans are primarily mediated by its HMW isoform. Posttranslational modifications play an important role in regulating activity and complex formation of adiponectin. Phosphorylation is considered to be another most common posttranslational modification that may alter the activity, life span, or cellular localization of proteins.

Characterization of a diet-induced obesity rat model for periodontal research.

Obesity is associated with periodontitis, but the mechanisms underlying this association have yet to be unraveled. The present investigation was to evaluate a common rat model, in which obesity is induced by high-fat, high-sucrose diet (HFSD), for its applicability in periodontal research. Ten male Wistar rats were fed a 3-month HFSD along with a matching control group. Afterwards, the body weight, adipocyte morphology, leptin and adiponectin levels in adipose tissue, gingiva, and serum as well as the serum levels of triglyceride, cholesterol, and glucose were analyzed. For statistical analyses, parametric and non-parametric tests were applied (p < 0.05). Body weight was significantly higher in the HFSD group after dieting as compared to control. HFSD caused a significant increase in serum triglyceride, low-density lipoprotein cholesterol, and leptin levels and a significant decrease in high-density lipoprotein cholesterol. Furthermore, adipose tissue from HFSD rats exhibited significantly larger adipocytes, displayed a significant upregulation of leptin and, surprisingly, elevated adiponectin levels, which is in contrast to chronic obesity in humans. Although leptin and adiponectin were also observed in gingival biopsies, no obvious differences between the groups were found. Although this rat diet-induced obesity model is characterized by changes typical of obesity, it also has limitations, which have to be considered when data, especially with regard to adipokines, are extrapolated to humans. The rodent diet-induced obesity model may be useful for unraveling pathomechanisms underlying the association between obesity and periodontal destruction but conclusions have to be drawn with caution.

Betaine attenuates chronic alcohol-induced fatty liver by broadly regulating hepatic lipid metabolism

Betaine has previously been demonstrated to protect the liver against alcohol-induced fat accumulation. However, the mechanism through which betaine affects alcohol-induced hepatic lipid metabolic disorders has not been extensively studied. The present study aimed to investigate the effect of betaine on alcoholic simple fatty liver and hepatic lipid metabolism disorders. A total of 36 rats were randomly divided into control, ethanol and ethanol + betaine groups. Liver function, morphological alterations, lipid content and tumor necrosis factor (TNF)-α levels were determined. Hepatic expression levels of diacylglycerol acyltransferase (DGAT) 1, DGAT2, sterol regulatory element binding protein (SREBP)-1c, SREBP-2, fatty acid synthase (FAS), 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase, peroxisome proliferator-activated receptor λ coactivator (PGC)-1α, adiponectin receptor (AdipoR) 1 and AdipoR2 were quantified. Serum and adipose tissue adiponectin levels were assessed using an enzyme-linked immunoassay. The results demonstrated that alcohol-induced ultramicrostructural alterations in hepatocytes, including the presence of lipid droplets and swollen mitochondria, were attenuated by betaine. Hepatic triglyceride, free fatty acid, total cholesterol and cholesterol ester contents and the expression of DGAT1, DGAT2, SREBP-1c, SREBP-2, FAS and HMG-CoA reductase were increased following ethanol consumption, however were maintained at control levels following betaine supplementation. Alcohol-induced decreases in hepatic PGC-1α mRNA levels and serum and adipose tissue adiponectin concentrations were prevented by betaine. The downregulation of hepatic AdipoR1 which resulted from alcohol exposure was partially attenuated by betaine. No significant differences in liver function, TNF-α, phospholipid and AdipoR2 levels were observed among the control, ethanol and ethanol + betaine groups. Overall, these results indicated that betaine attenuated the alcoholic simple fatty liver by improving hepatic lipid metabolism via suppression of DGAT1, DGAT2, SREBP-1c, FAS, SREBP-2 and HMG-CoA reductase and upregulation of PGC-1α.

Rosiglitazone Improves Insulin Resistance Mediated by 10,12 Conjugated Linoleic Acid in a Male Mouse Model of Metabolic Syndrome.

Trans-10, cis-12 conjugated linoleic acid (10,12 CLA) is a dietary fatty acid that promotes weight loss and disproportionate fat loss. Obese mice fed a high-fat, high-sucrose (HFHS) diet containing 10,12 CLA are resistant to weight gain and contain markedly reduced subcutaneous fat and adiponectin, with a concurrent lack of improvement in insulin sensitivity despite significant weight loss. Taken together, 10,12 CLA promotes a phenotype resembling peroxisome proliferator-activated receptor (PPAR)γ antagonism. Because thiazolidinediones such as rosiglitazone (Rosi) are used clinically to improve insulin sensitivity by activating PPARγ, with particular efficacy in subcutaneous white adipose tissue, we hypothesized that Rosi would improve glucose metabolism in mice losing weight with 10,12 CLA. Obese low-density lipoprotein receptor-deficient mice were fed a HFHS control diet, or supplemented with 1% 10,12 CLA with or without Rosi (10 mg/kg) for 8 weeks. Body composition, glucose and insulin tolerance tests, tissue gene expression, and plasma lipid analyses were performed. Mice consuming 10,12 CLA with Rosi lost weight and body fat compared with control groups, but with a healthier redistribution of body fat toward more subcutaneous adipose tissue than with 10,12 CLA alone. Further, Rosi improved 10,12 CLA-mediated insulin resistance parameters and increased plasma and subcutaneous adipose tissue adiponectin levels without adverse effects on plasma or hepatic lipids. We conclude that cotreatment of mice with 10,12 CLA and Rosi promotes fat loss with a healthier fat distribution that leads to improved insulin sensitivity, suggesting that the combination treatment strategy of 10,12 CLA with Rosi could have therapeutic potential for obesity treatment.

GLUCOMANNAN AND GLUCOMANNAN PLUS SPIRULINA-ENRICHED SQUID-SURIMI ADDED TO HIGH SATURATED DIET AFFECT GLYCEMIA, PLASMA AND ADIPOSE LEPTIN AND ADIPONECTIN LEVELS IN GROWING FA/FA RATS.

Type 2 diabetes is a very prevalent chronic disease. Among dietary factors for its prevention and treatment, interest has grown in satiating fibre (konjac glucomannan) and spirulina. Our previous studies suggest that glucomannan itself and/or in conjunction to spirulina displayed hypolipemic and antioxidant effects when incorporated to squid surimi as functional ingredients. The present study aims to determine whether glucomannan- enriched or glucomannan plus spirulina-enriched squid-surimi improve plasma glucose and insulin levels in Zucker fa/fa rats fed a high saturated fat diet. Twenty four growing rats, divided into three groups, were given modified AIN-93M diets for seven weeks: 30% squid-surimi control diet (C), 30% glucomannan-enriched squid-surimi diet (G) and 30% glucomannan plus spirulina-enriched squid-surimi diet (GS). All rats became hyperglycemics and hyperinsulinemics, but G and GS diets induced significantly lower glucose levels (20%; p < 0.05) but did not modify insulinemia with respect to C diet. GS animals showed higher HOMA-D (p < 0.05) than C ones suggesting increased insulin availability. Plasma leptin and adiponectin decreased in G and GS vs. C group (p < 0.05). Adipose adiponectin increased significantly in G and GS vs. C rats (16-20 times, p < 0.01). Leptin in adipose tissue was higher in GS vs. G group (p < 0.05). In conclusion, both glucomannan-diets were able to reduce hyperglycemia and increase adipose tissue adiponectin levels in fa/fa rats, suggesting an anti-hypertrophic and insulin-sensitizing adipokine effect in this tissue. Spirulina inclusion increased insulin availability. Although results are promising, the utility of consuming glucomannan surimis as part of usual diets demands future studies.

Gene expression levels of Casein kinase 1 (CK1) isoforms are correlated to adiponectin levels in adipose tissue of morbid obese patients and site-specific phosphorylation mediated by CK1 influences multimerization of adiponectin

White adipose tissue has now been recognized as an important endocrine organ secreting bioactive molecules termed adipocytokines. In obesity, anti-inflammatory adipocytokines like adiponectin are decreased while pro-inflammatory factors are over-produced. These changes contribute to the development of insulin resistance and obesity-associated diseases. Since members of the casein kinase 1 (CK1) family are involved in the regulation of various signaling pathways we ask here whether they are able to modulate the functions of adiponectin. We show that CK1δ and ε are expressed in adipose tissue and that the expression of CK1 isoforms correlates with that of adiponectin. Furthermore, adiponectin co-immunoprecipitates with CK1δ and CK1ε and is phosphorylated by CK1δ at serine 174 and threonine 235, thereby influencing the formation of adiponectin oligomeric complexes. Furthermore, inhibition of CK1δ in human adipocytes by IC261 leads to an increase in basal and insulin-stimulated glucose uptake. In summary, our data indicate that site-specific phosphorylation of adiponectin, especially at sites targeted by CK1δ in vitro, provides an additional regulatory mechanism for modulating adiponectin complex formation and function.

HO-1 Upregulation Attenuates Adipocyte Dysfunction, Obesity, and Isoprostane Levels in Mice Fed High Fructose Diets.

Background. Fructose metabolism is an unregulated metabolic pathway and excessive fructose consumption is known to activate ROS. HO-1 is a potent antioxidant gene that plays a key role in decreasing ROS and isoprostanes. We examined whether the fructose-mediated increase in adipocyte dysfunction involves an increase in isoprostanes and that pharmacological induction of HO-1 would decrease both isoprostane levels and adipogenesis. Methods and Results. We examined the effect of fructose, on adipogenesis in human MSCs in the presence and absence of CoPP, an inducer of HO-1. Fructose increased adipogenesis and the number of large lipid droplets while decreasing the number of small lipid droplets (P < 0.05). Levels of heme and isoprostane in fructose treated MSC-derived adipocytes were increased. CoPP reversed these effects and markedly increased HO-1 and the Wnt signaling pathway. The high fructose diet increased heme levels in adipose tissue and increased circulating isoprostane levels (P < 0.05 versus control). Fructose diets decreased HO-1 and adiponectin levels in adipose tissue. Induction of HO-1 by CoPP decreased isoprostane synthesis (P < 0.05 versus fructose). Conclusion. Fructose treatment resulted in increased isoprostane production and adipocyte dysfunction, which was reversed by the increased expression of HO-1.

Allergen exposure induces inflammation and affects adiponectin levels in adipose tissue

This study investigates whether allergen exposure elevates the risk of diabetes or cardiovascular diseases using acute OVA (Ovalbumin) allergen exposure model. We hypothesize that exposure to allergen can induce adipose tissue inflammation and affect adiponectin levels. An intranasal challenge with OVA male C57BL/6 mice was performed at dose of 6.25, 12.5, 25, 50 and 100μg, and compared to which challenge with PBS (phosphate buffered saline). Results showed that acute OVA exposure did not only cause airway inflammation in study mice, but also decreased serum adiponectin levels with a dose-response effect. When examining the gonadal adipose tissues, there was no significantly difference of adiponectin mRNA in OVA challenged mice compared to those PBS challenged, but lower inguinal adiponectin mRNA expression was found compared to those PBS-challenged, and had a good relationship with the serum adiponectin. Inguinal adipose tissues of OVA challenged mice, had significantly lower adipose tissue weight, and higher TNF-α expression without statistical significance. Our data indicate that acute OVA exposure appears to affect the characteristics of adipose tissues, and change the adiponectin levels in serum and adipose tissues. Allergen exposure may be considered a potential risk factor for presenting diabetes or cardiovascular diseases.

Baseline epicardial adipose tissue adiponectin levels predict cardiovascular outcomes: A long-term follow-up study

ObjectiveEpicardial adipose tissue (EAT) produces a wide range of adipokines and has recently been linked to the physiopathology of cardiovascular (CV) and metabolic diseases. We aimed to study whether EAT and subcutaneous (SAT) adiponectin and leptin expression levels are associated with CV complications during long-term follow-up. Methods and resultsEAT and SAT samples were obtained during surgery – mainly CABG (n=77) – from 137 patients (mean age 69.9years, 31% women). Adiponectin and leptin mRNA levels were analyzed by RT-PCR. Plasma adiponectin levels were determined in a subsample of subjects (n=43). Thirty-four patients developed CV complications during 41 (SD 23) months of mean follow-up. Patients with CV events had lower EAT and SAT adiponectin levels at baseline (12.4 (3.0) vs. 15.7 (3.8) a.u., P=0.001; and 13.7 (2.6) vs. 15.7 (4.4) a.u., P=0.048, respectively). However, baseline EAT and SAT leptin levels and plasma adiponectin levels were not significantly different between patients with/without CV events during follow-up. Cox proportional hazards models adjusting for covariates in stages revealed that only baseline EAT adiponectin levels and heart failure could predict CV events. ConclusionsEAT adiponectin levels are strong predictors of CV prognosis in patients with CV diseases. EAT is likely to play a major role in the development of CV complications mainly through local effects.

Pharmacological IKK2 inhibition blocks liver steatosis and initiation of non-alcoholic steatohepatitis

Background: Non-alcoholic-steatohepatitis (NASH) leading to fibrosis, end-stage cirrhosis and hepatocellular carcinoma is an increasing health problem in the Western world. Thus, the need for new therapeutic approaches is increasing. IKK2...

Role of Insulin Receptor Substrate-1 Serine 307 Phosphorylation and Adiponectin in Adipose Tissue Insulin Resistance in Late Pregnancy

Insulin resistance is a hallmark of late pregnancy both in human and rat. Adipose tissue is one of the tissues that most actively contributes to this reduced insulin sensitivity. The aim of the present study was to characterize the molecular mechanisms of insulin resistance in adipose tissue at late pregnancy. To this end, we analyzed the insulin signaling cascade in lumbar adipose tissue of nonpregnant and pregnant (d 20) rats both under basal and insulin-stimulated conditions. We found that the levels of relevant signaling proteins, such as insulin receptor (IR), IR substrate-1 (IRS-1), phosphatidylinositol 3-kinase, 3-phosphoinositide-dependent kinase-1, ERK1/2, and phosphatase and tensin homolog (PTEN) did not change at late pregnancy. However, insulin-stimulated tyrosine phosphorylation of both IR and IRS-1 were significantly decreased, coincident with decreased IRS-1/p85 association and impaired phosphorylation of AKR mouse thymoma viral protooncogene (Akt) and ERK1/2. This impaired activation of IRS-1 occurred together with an increase of IRS-1 phosphorylation at serine 307 and a decrease in adiponectin levels. To corroborate the role of IRS-1 in adipose tissue insulin resistance during pregnancy, we treated pregnant rats with the antidiabetic drug englitazone. Englitazone improved glucose tolerance, and this pharmacological reversal of insulin resistance was paralleled by an increase of adiponectin levels in adipose tissue as well as by a reduction of IRS-1 serine phosphorylation. Furthermore, the impaired insulin-stimulated tyrosine phosphorylation of IRS-1 in adipose tissue of pregnant animals could be restored ex vivo by treating isolated adipocytes with adiponectin. Together, our findings support a role for adiponectin and serine phosphorylation of IRS-1 in the modulation of insulin resistance in adipose tissue at late pregnancy.

Effects of Antidiabetic Treatment with Metformin and Insulin on Serum and Adipose Tissue Adiponectin Levels in db/db Mice

Decreased circulating levels of adiponectin, a novel adipose-derived adipocytokine, in obesity possibly contribute to the development of insulin resistance which is a major factor in the pathogenesis of type 2 diabetes. The present study was conducted to examine whether circulating and adipose tissue adiponectin levels are modulated by chronic treatment with metformin and intensive treatment with insulin in murine models of obesity and type 2 diabetes, db/db mice with a C57BL/KsJ genetic background. Nine-week-old male db/db mice were treated with metformin, insulin, and vehicle for 4 weeks. Expectedly, metformin treatment led to inhibition of weight gain and improvement of hyperinsulinemia. Insulin treatment lowered fasting blood glucose levels to normal values, although it sustained hyperinsulinemic state. However, after 4 weeks of treatment, serum adiponectin levels were not significantly elevated in either metformin-treated or insulin-treated db/db mouse group (14.2 +/- 0.7 and 16.7 +/- 1.0 microg/ml, respectively) compared to vehicle-treated group (14.9 +/- 0.6 microg/ml). Similarly, adipose tissue adiponectin levels determined by Western blot analysis were not increased in either metformin-treated or insulin-treated group relative to vehicle-treated group. Recent studies have shown that adiponectin possibly has the same physiological effects on lipid and glucose metabolism that metformin has. Therefore, an elevation in blood concentration of metformin following the treatment might lead to suppression in adiponectin synthesis in adipose tissue, independent of inhibition in weight gain and improvement in hyperinsulinemia by metformin treatment. The present results indicate that adiponectin is not involved in the mechanism by which metformin treatment enhances insulin sensitivity. Moreover, our results suggest that adiponectin synthesis in adipose tissue may be suppressed under hyperinsulinemic state sustained by insulin treatment, even though hyperglycemia is markedly reduced. We conclude that antidiabetic treatment with metformin and insulin does not affect circulating and adipose tissue adiponectin levels.