Serum High Molecular Weight Adiponectin Levels Research Articles

Plasma free amino acid profiles are associated with serum high molecular weight adiponectin levels in Japanese medical check-up population without type 2 diabetes mellitus

To prevent the progression of type 2 diabetes mellitus (T2DM), early detection and intervention are important. Several studies have already shown that the serum adiponectin level could be useful for evaluating the future risk of T2DM. Recently, plasma free amino acid (PFAA) concentrations have also emerged as potential biomarkers that predict the future onset of T2DM. In this study, we aimed to further characterise PFAA profiles by elucidating the association with the serum high molecular weight (HMW) adiponectin level in this cross-sectional study. A total of 1000 Japanese subjects who underwent medical check-ups were enrolled, and their plasma concentrations of 21 amino acids and clinical parameters were measured. The subjects without T2DM were divided into quartiles (Q1-4) by serum HMW adiponectin level, and the association with between PFAA concentrations was analysed. Concentrations of glutamate, alanine, proline, tyrosine, histidine, methionine, lysine, branched-chain amino acids (BCAAs) and tryptophan varied significantly according to the adiponectin quartile. Furthermore, serum adiponectin levels showed significant inverse correlations with these amino acids. The change in the PFAA profile in the group with the lowest adiponectin concentrations (Q1) was similar to that of T2DM patients. Although both adiponectin levels and PFAA concentrations are known to be altered by the accumulation of visceral fat and insulin resistance, the levels of glutamate, BCAA, lysine and tryptophan remain significantly associated with adiponectin level after adjustment for age, body mass index and homeostasis model assessment of insulin resistance, showing the direct association between PFAA concentrations and the serum HMW adiponectin level. Registration number: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) UMIN000029920, registered on Nov 13th 2017 (prospectively registered).

Assessment of the Relationship Between Serum High Molecular Weight Adiponectin Hormone Levels and Insulin Resistance in Patients with Polycystic Ovary Syndrome.

The purpose of this study was to assess the rate of insulin resistance (IR) and the relationship between IR and high-molecular weight adiponectin (HMWA) in patients with polycystic ovary syndrome (PCOS). A cross sectional study involving 43 women with PCOS and 39 normal women was carried out over a period of nine months. Fasting glucose and insulin levels, lipid parameters and androgen levels were measured in all serum samples. HMWA was determined by enzyme-linked immunosorbent assay and IR was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR) index. The IR was more prevalent in the PCOS group than in the controls (p=0.002). Dehydroepiandrosterone sulfate, sex hormone binding globulin, free androgen index, total testosterone, insulin, and HOMA-IR levels were significantly higher in the PCOS group as compared to the control group (all p<0.05). Moreover, HMWA was significantly lower and negatively correlated with the clinical and biochemical hyperandrogenism in the PCOS group. HMWA and HOMA-IR were also associated with triglyceride, body mass index, and fat mass in this group. ROC curve analyses demonstrated that the AUC, indicative of the HMWA value for discriminating PCOS with IR, was 0.725, with a confidence interval of 0.615-0.835 (p=0.001). The serum HMWA levels are lower in patients with PCOS, which suggest that HMWA might be involved in the pathogenesis of PCOS. We also conclude that HMWA might be a strong determinant of IR in PCOS patients.

Association of leptin, resistin, and high-molecular-weight adiponectin levels with psoriasis area and severity index scores, obesity, and insulin resistance in psoriasis patients

Background: Psoriasis is frequently associated with obesity and cardiovascular diseases. Adipocytokines have been implicated in the pathogenesis of psoriasis and its cardiometabolic comorbidities. Objectives: The aim of this study was to assess the roles of leptin, resistin, and high-molecular-weight (HMW) adiponectin in psoriasis as well as their relationship with Psoriasis Area and Severity Index (PASI), obesity, and insulin resistance. Materials and Methods: Forty-six psoriasis patients and equivalent age-, sex-, and body mass index (BMI)-matched controls were recruited in this study. PASI, waist and hip circumferences, and waist/hip ratio (WHR) were recorded, and total body fat mass (TBFM) values were measured using a bioimpedance body composition analyzer. Fasting serum leptin, resistin, and HMW adiponectin levels were measured, and homeostasis model assessment values for insulin resistance (HOMA-IR) were calculated. Results: After the adjustment for anthropometric variables, leptin levels did not differ significantly between the groups (P = 0.736). The patient group showed significantly elevated resistin and lower HMW adiponectin levels (P = 0.007, P= 0.010, respectively). The correlation of serum leptin, resistin, and HMW adiponectin with PASI was not significant (r = −0.100, P= 0.506; r = −0.053, P= 0.726; r = −0.103, P= 0.494, respectively). HOMA-IR positively correlated with leptin and negatively correlated with HMW adiponectin (r = 0.426, P

Influence of serum HMW adiponectin level in patients with pregnancy-induced hypertension syndrome on the occurrence of eclampsia in secondary pregnancy.

In the present study, we studied the influence of serum high-molecular weight adiponectin (HMWA) levels in patients with pregnancy-induced hypertension (PIH) on the occurrence of eclampsia in secondary pregnancy and its related mechanisms. In total, 130 patients who were diagnosed with PIH for the first time were selected for this study; the median interval of the secondary pregnancy was 28.5 months. The serum HMWA and leptin levels both times were detected, and the insulin resistance indexes (HOMA-IR) were calculated. The serum inflammatory indexes in the secondary pregnancy included interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels, and the oxidative stress indexes included methane dicarboxylic aldehyde (MDA) and oxidized low-density lipoprotein (ox-LDL) levels. The expression levels of adiponectin receptor 2 and cyclooxygenase-2 (COX-2) in placental tissue were detected. In secondary pregnancy, there were a total of 20 cases of eclampsia (15.38%), including 2 cases of mild PIH, 8 cases of moderate PIH and 10 cases of severe PIH; differences were statistically significant when compared to patients without eclampsia (p<0.001). The serum HMWA levels in patients with severe PIH in the first pregnancy were significantly lower than those in patients with mild and moderate PIH, and the serum levels in patients with mild PIH were the highest. The leptin levels in patients with severe PIH were significantly higher than those in patients with mild and moderate PIH, and the leptin levels in patients with mild PIH were the lowest (p<0.05). The HMWA levels in patients with eclampsia in the secondary pregnancy was significantly lower than those in patients without eclampsia, and the leptin levels in patients with eclampsia were significantly increased. The HMWA levels in patients with eclampsia in the secondary pregnancy were lower than that in the first pregnancy, whereas the leptin levels were higher than that in the first pregnancy (p<0.05). HOMA-IR, IL-6, TNF-α, MDA and ox-LDL levels in patients with eclampsia were significantly higher than those in patients without eclampsia (p<0.05), and the adiponectin receptor 2 and COX-2 expression levels in the placental tissue were significantly higher than those in patients without eclampsia (p<0.05). Therefore, the serum HMWA levels are closely related to the occurrence of eclampsia in PIH patients in secondary pregnancy, and it influences insulin resistance, inflammatory response and oxidative stress response, which is correlated with increased adiponectin receptor 2 and COX-2 protein expression in placental tissue. Consequently, HMWA may be an important target for the intervention of preventing eclampsia for PIH patients in secondary pregnancy.

Effect of berberine on the ratio of high-molecular weight adiponectin to total adiponectin and adiponectin receptors expressions in high-fat diet fed rats.

To assess the effects of berberine (BBR) on high-molecular weight (HMW) adiponectin and adiponectin receptors (adipoR1/adipoR2) expressions in high-fat (HF) diet fed rats. Forty Wistar male rats were randomly assigned into a normal diet fed group and three HF diet (fat for 45% calories) fed groups (n=10 for each group). All rats underwent 12 weeks of feeding. After 4 weeks feeding, rats in the two of three HF diet fed groups were treated with 150 mg·kg-1·day-1 BBR (HF+LBBR group) and 380 mg·kg-1·day-1 BBR (HF+HBBR group) by gavage once a day respectively for the next 8 weeks while the rats in other groups treated with vehicle (NF+Veh and HF+Veh). Body weight and food intake were observed and recorded on daily basis. At the end of 12 weeks, the blood, liver, epididymal fat tissues and quadriceps femoris muscles were collected. Fasting insulin, plasma fasting glucose, serum free fatty acid (FFA), total adiponectin and HMW adiponectin levels were measured by enzyme linked immunosorbent assay method. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to determine the insulinsensitizing. Meanwhile the homeostasis model assessment (HOMA) method was used to determine insulin resistance (HOMA-IR). The expressions of adipoR1, adipoR2 and adenosine monophophate activated protein kinase (AMPK) phosphorylation level in skeletal muscle and liver tissue were detected by Western blot. Liver and kidney toxicity were evaluated during treatment. The body weight of rats in high- or low-dose BBR group reduced as well as HOMA-IR, FFA concentrations and fasting insulin levels decreased compared with HF+Veh group (P<0.05). BBR also increased the ratio of HMW to total adiponectin in high fat-fed rats compared with rats in the HF+Veh group. High- and low-dose BBR increased adipoR1 expression in skeletal muscle by over 6- and 2-fold (P<0.05), respectively, and high-dose BBR also increased adipoR2 expression in liver tissue by over 2-fold (P<0.05). BBR significantly increased AMPK phosphorylation in HF diet rats compared with normal diet rats (P<0.05). The ratio of HMW to total adiponectin was inversely correlated with HOMA-IR (r=-0.52, P=0.001). Meantime, no liver and kidney toxicity was found in high fat-fed rats that treated by BBR. Berberine may improve insulin resistance by increasing the expression of adiponectin receptors and the ratio of HMW to total adiponectin.

Serum high‐molecular‐weight adiponectin level and incident dementia in patients with vascular risk factors

The involvement of metabolic factors in the development of dementia has received much attention. However, previous studies have yielded conflicting results regarding how blood adipocytokine level impacts cognitive decline and dementia. This study aimed to clarify whether serum high-molecular-weight (HMW) adiponectin level is related to incident dementia. Data were from 466 patients (mean age 67.8 years, male 57%)--who had normal cognitive function and received brain magnetic resonance imaging--from amongst the 1106 patients in the Osaka Follow-up Study for Carotid Atherosclerosis, Part 2, a prospective cohort study of cardiovascular events and dementia amongst patients with vascular risk factors enrolled between 2001 and 2009. Baseline HMW adiponectin levels were measured using frozen serum. Dementia occurrence was examined in June 2013. Serum HMW adiponectin level was 4.33 ± 2.95 μg/ml; the levels were lower in men than in women and negatively correlated with body mass index. During the follow-up period (median 6.9 years), 47 patients had incident dementia including Alzheimer's disease dementia (27), vascular dementia (13), mixed dementia (four), other dementia (three). Risks of dementia in patients with high versus low HMW adiponectin levels were almost identical (P = 0.689). No association was found between adiponectin levels and Alzheimer's disease dementia or vascular dementia in the whole group or amongst men and women separately. This study demonstrated that serum HMW adiponectin level has little association with future dementia. Determination of metabolic factors involved in dementia requires evaluation of other biomarkers or parameters.

The effects of adiponectin and inflammatory cytokines on diabetic vascular complications in obese and non-obese patients with type 2 diabetes mellitus

AimsTo evaluate the associations between inflammatory cytokines and adiponectin and various vascular complications in type 2 diabetes mellitus (T2DM). MethodsA total of 761 patients with T2DM were divided into a non-obese group and an obese group to enable the effects of obesity and T2DM on vascular complications to be differentiated. The serum levels of circulating inflammatory cytokines, that is, tumor necrosis factor (TNF)-α, and interleukin (IL)-6, total adiponectin, and high molecular weight (HMW) adiponectin were measured, and carotid intima media thickness (IMT), the presence of carotid plaque, and the severities of retinopathy and nephropathy, were assessed. ResultsThe obese group had significantly lower serum total and HMW adiponectin levels than the non-obese group. In the obese group, serum levels of total and HMW adiponectin, and TNF-α were significantly higher in patients with proliferative retinopathy than in those without retinopathy after adjusting for covariates. In the non-obese group, only IL-6 levels were significantly higher in patients with proliferative retinopathy than in those without. Serum levels of total and HMW adiponectin were significantly higher in patients with macroalbuminuria than in those with normoalbuminuria. No significant difference of three cytokines levels were observed depending on the carotid IMT or the presence of plaque. Logistic regression analysis revealed that serum total adiponectin (OR=1.209, P=0.038), diabetes duration (OR=1.230, P=0.014), and HbA1c (OR=2.359, P=0.006) were significantly associated with proliferative retinopathy in the obese group. ConclusionThe study shows total adiponectin may influence proliferative retinopathy in obese patient with T2DM.

Association of adiponectin gene polymorphism with nonalcoholic fatty liver disease in Taiwanese patients with type 2 diabetes.

ObjectivePatients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) have a higher prevalence of cardiovascular diseases. In this study we investigated the frequency of single nucleotide polymorphisms (SNPs) of several candidate genes associated with NAFLD in Taiwanese patients with type 2 diabetes mellitus (DM) and NAFLD and in those with DM but without fatty liver disease.MethodsWe enrolled 350 patients with type 2 DM and NAFLD and 209 patients with DM but without NAFLD. Body mass index (BMI), % body fat (% BF), glycated hemoglobin (HbA1c), high molecular weight (HMW) isoform of adiponectin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels were measured. Thirteen SNPs in 5 genes (adiponectin, leptin, peroxisome proliferator-activated receptor alpha, adiponutrin/patatin-like phospholipase domain-containing protein 3 and peroxisome proliferator-activated receptor γ co-activator 1α ) were measured.ResultsOnly adiponectin rs266729 polymorphism was associated with susceptibility to NAFLD (p = 0.001). Subgroup analysis revealed that the proportion of subjects with homozygous genotype GG was higher in patients with NAFLD (31%) than in controls (11%) and that the proportions of heterozygous CG and homozygous CC were higher in controls (37% and 52%, respectively) than in patients with NAFLD (33% and 36%, respectively). Patients with NAFLD carrying the GG genotype of rs266729 showed significantly lower serum HMW adiponectin levels than patients carrying the GC or CC genotype (3.75±0.37 vs. 3.99±0.66 vs. 4.79±0.58 μg/ml, p< 0.001). Body fat and serum HMW adiponectin levels were the strongest predictors of developing NAFLD (p < 0.001 and 0.004, respectively).ConclusionsIn patients with type 2 diabetes gene polymorphism of adiponectin rs266729 is associated with risk of NAFLD. G allele of rs266729 is associated with hypoadiponectinemia. Low serum adiponectin level may precipitate liver steatosis in patients with type 2 diabetes.

Switching from Sitagliptin to Alogliptin under Treatment with Pioglitazone Increases High Molecular Weight Adiponectin in Type 2 Diabetes: A Prospective Observational Study

Background: There are few clinical trials addressing the difference in pleiotropic effects among dipeptidyl peptidase (DPP)-4 inhibitors. We aimed to identify difference in effects on biochemical markers of inflammation, oxidative stress, and atherosclerosis between two DPP-4 inhibitors in patients with type 2 diabetes. Methods: We prospectively observed twenty subjects with type 2 diabetes before and after a practical medication change from a treatment with pioglitazone and sitagliptin 50 mg to a combination tablet containing the same dose of pioglitazone and alogliptin 25mg, which was actually identical to switching from sitagliptin to alogliptin. After 3 months, changes from baseline in clinical data and various biochemical markers were evaluated. In particular, body mass index (BMI) and hemoglobin A1c (HbA1c) were additionally followed after 12 months for evaluation of chronic outcomes. Results: Among markers, serum levels of high molecular weight (HMW) adiponectin significantly increased from 6.9 ± 3.6 μg/ml to 8.2 ± 4.0 μg/ml (P = 0.0045). Although no clinical data changed after 3 months, significant improvements in HbA1c and BMI were observed after 12 months. Their rates of changes tended to inversely correlate with the increased percentages of serum HMW adiponectin levels during initial 3 months, but they did not reach statistical significance. Conclusions: In spite of pretreatment with pioglitazone, additional increase in serum HMW adiponectin levels was demonstrated after switching from sitagliptin to alogliptin. Given multiple favorable roles of adiponectin in metabolic and cardiovascular states, alogliptin, at least when combined with pioglitazone, would be beneficial in treatment of type 2 diabetes.

Adding glimepiride to current insulin therapy increases high-molecular weight adiponectin levels to improve glycemic control in poorly controlled type 2 diabetes.

BackgroundTo observe the efficacy and safety of adding glimepiride to established insulin therapy in poorly controlled type 2 diabetes (T2D) and to assess the relationship of changes in the serum high-molecular weight (HMW) adiponectin levels and glycemic control after glimepiride treatment.MethodsFifty-six subjects with poorly controlled insulin-treated T2D were randomly assigned to either the glimepiride-added group (the group A, n = 29) or the insulin-increasing group (the group B, n = 27) while continuing current insulin-based therapy. Glycosylated hemoglobin (HbA1c) value, daily insulin dose, body weight, waist circumference, plasma lipid concentration, serum HMW adiponectin level and the number of hypoglycemic events were evaluated before and after treatment.ResultsAt the end of study, insulin doses were significantly reduced, and the mean HbA1c, fasting blood glucose (FBG) and 2-hour postprandial blood glucose (P2BG) were improved greater in the group A compared with the group B. The serum HMW adiponectin levels were significantly increased in the group A compared with the group B. Most importantly, we found that changes in HbA1c were inversely correlated with changes in serum HMW adiponectin in the group A (r = −0.452, p = 0.02).ConclusionsAdding glimepiride to current insulin treatment led to better improvement in glycemic control with a significant smaller daily insulin dose, and the increases in the serum HMW adiponectin levels may directly contribute to improvement glycemic control.

Relationship of serum isoflavone, insulin and adiponectin levels with breast cancer risk

Obesity is one of the well-known risk factors of breast cancer. Accumulating evidence suggests that adiponectin, an obesity-related hormone, is inversely associated with breast cancer risk, particularly in postmenopausal women. Obesity is also associated with high levels of insulin. In addition, studies have suggested that the soy isoflavones present in the traditional Japanese diet have been associated with decreased risk of breast cancer. However, there is no study that has assessed associations between serum levels of isoflavones, insulin, adiponectin and the risk of breast cancer all together with menopausal status. In a case-control study of 63 histologically confirmed breast cancer patients and 76 controls, serum isoflavone, insulin, and high-molecular-weight (HMW) adiponectin levels and breast cancer risk were examined for their association with breast cancer risk after adjustment for various risk factors. Women in the highest tertile of serum HMW adiponectin levels were associated with a statistically significant decreased risk for breast cancer compared with women in the lowest tertile [odds ratio (OR), 0.09; 95% confidence interval (CI) 0.03-0.33]. This association was observed in postmenopausal women (OR 0.06; 95% CI 0.01-0.28), but not in premenopausal women. The observed associations were independent of possible effects of insulin, body mass index, and known risk factors for breast cancer. Serum isoflavones and insulin levels were not associated with breast cancer risk. This study suggests that high serumHMW adiponectin levels are significantly associated with a decreased risk for breast cancer. Our result support the hypothesis that serum adiponectin may act as a potential biomarker for breast cancer.

Effects of pravastatin on serum adiponectin levels in female patients with type 2 diabetes mellitus

ObjectivePravastatin has been reported to elevate circulating adiponectin levels in patients with various insulin resistant state, hypertension, coronary artery disease, and hypercholesterolemia. This study aimed to evaluate whether pravastatin increase serum total and high molecular weight adiponectin levels and improve insulin sensitivity in female patients with type 2 diabetes mellitus and hypercholesterolemia. Patients and designThis study was designed as a multicenter, double-blind, placebo-controlled, factorial randomized trial (placebo and pravastatin at 20 or 40 mg per day). A total of 73 female patients with type 2 diabetes and hypercholesterolemia were enrolled. Changes in total and high molecular weight (HMW) serum adiponectin levels, the ratio of HMW adiponectin to total adiponectin, insulin sensitivity measured by homeostasis model assessment of insulin resistance (HOMA-IR) and lipid profiles were evaluated after 16 weeks in each group. ResultsTotal cholesterol and low-density lipoprotein (LDL) cholesterol levels were significantly reduced after 16 weeks in the pravastatin 20 mg and 40 mg treatment groups compared with the placebo group (P = 0.008 and P = 0.004, respectively). However, there were no significant differences between the 20 mg and 40 mg pravastatin treatment groups in terms of total adiponectin and HMW adiponectin serum levels, as well as insulin sensitivity (P = 0.348 and P = 0.991). ConclusionsIn female patients with type 2 diabetes and hypercholesterolemia, 16 weeks pravastatin therapy did not affect on serum total adiponectin or HMW adiponectin levels.

Serum adipokine profiles in Kawasaki disease

Adipokines are cytokines derived from adipose tissue. Recently it has been established that adipokines are closely linked to the pathophysiology of not only metabolic diseases, such as diabetes mellitus, obesity, and atherosclerosis, but also to inflammation and immune diseases. In this study we measured serum levels of adipokines in patients with acute Kawasaki disease to investigate the role of adipokines in the pathophysiology of Kawasaki disease. Serum resistin, high-molecular-weight (HMW) adiponectin, leptin, and visfatin levels were measured by enzyme-linked immunosorbent assay in a total of 117 subjects: 56 patients with acute Kawasaki disease, 30 healthy children, and 31 patients with acute infectious diseases. Serum resistin levels in patients with Kawasaki disease were significantly higher than those of healthy children and patients with acute infectious diseases. In contrast, mean serum HMW adiponectin, leptin, and visfatin levels in patients with Kawasaki disease exhibited no statistically significant differences compared with those in healthy children and patients with infectious diseases. Serum resistin levels decreased significantly after administration of intravenous immune globulin. Serum resistin levels on admission were significantly higher in nonresponders compared with responders to intravenous immune globulin therapy. A multivariate model revealed that C-reactive protein was a factor that was significantly related to elevated serum resistin level in patients with Kawasaki disease. In patients with Kawasaki disease, serum resistin levels were elevated, but decreased to nearly normal after intravenous administration of immune globulin. In contrast, serum HMW adiponectin, leptin, and visfatin levels showed no statistically significant changes. These findings suggest that resistin plays an important role, while other adipokines do not play a major role, in the pathogenesis of Kawasaki disease.

Total and High Molecular Weight Adiponectin and Hepatocellular Carcinoma with HCV Infection

BackgroundAdiponectin is shown to be inversely associated with development and progression of various cancers. We evaluated whether adiponectin level was associated with the prevalence and histological grade of hepatocellular carcinoma (HCC), and liver fibrosis in patients with hepatitis C virus (HCV) infection.MethodsA case-control study was conducted on 97 HCC patients (cases) and 97 patients (controls) matched for sex, Child-Pugh grade and platelet count in patients with HCV infection. The serum total and high molecular weight (HMW) adiponectin levels were measured by enzyme-linked immunosorbent assays and examined in their association with the prevalence of HCC. In addition, the relationship between these adiponectin levels and body mass index (BMI), progression of liver fibrosis, and histological grade of HCC was also evaluated. Liver fibrosis was assessed using the aspartate aminotransferase to platelet ratio index (APRI).ResultsThere were no significant differences in the serum total and HMW adiponectin levels between cases and controls. Moreover, there were no inverse associations between serum total and HMW adiponectin levels and BMI in both cases and controls. On the other hand, serum total and HMW adiponectin levels are positively correlated with APRI in both cases (r = 0.491, P<0.001 and r = 0.485, P<0.001, respectively) and controls (r = 0.482, P<0.001 and r = 0.476, P<0.001, respectively). Interestingly, lower serum total (OR 11.76, 95% CI: 2.97–46.66 [P<0.001]) and HMW (OR 10.24, CI: 2.80–37.40 [P<0.001] adiponectin levels were independent risk factors of worse histological grade of HCC.ConclusionsOur results suggested that serum total and HMW adiponectin levels were predictors of liver fibrosis, but not prevalence of HCC in patients with HCV infection. Moreover, low these adiponectin levels were significantly associated with worse histological grades.

Serum adipokine profiles in Kawasaki disease

Adipokines are cytokines derived from adipose tissue. Recently it has been established that adipokines are closely linked to the pathophysiology of not only metabolic diseases, such as diabetes mellitus, obesity, and atherosclerosis, but also to inflammation and immune diseases. In this study we measured serum levels of adipokines in patients with acute Kawasaki disease to investigate the role of adipokines in the pathophysiology of Kawasaki disease. Serum resistin, high-molecular-weight (HMW) adiponectin, leptin, and visfatin levels were measured by enzyme-linked immunosorbent assay in a total of 117 subjects: 56 patients with acute Kawasaki disease, 30 healthy children, and 31 patients with acute infectious diseases. Serum resistin levels in patients with Kawasaki disease were significantly higher than those of healthy children and patients with acute infectious diseases. In contrast, mean serum HMW adiponectin, leptin, and visfatin levels in patients with Kawasaki disease exhibited no statistically significant differences compared with those in healthy children and patients with infectious diseases. Serum resistin levels decreased significantly after administration of intravenous immune globulin. Serum resistin levels on admission were significantly higher in nonresponders compared with responders to intravenous immune globulin therapy. A multivariate model revealed that C-reactive protein was a factor that was significantly related to elevated serum resistin level in patients with Kawasaki disease. In patients with Kawasaki disease, serum resistin levels were elevated, but decreased to nearly normal after intravenous administration of immune globulin. In contrast, serum HMW adiponectin, leptin, and visfatin levels showed no statistically significant changes. These findings suggest that resistin plays an important role, while other adipokines do not play a major role, in the pathogenesis of Kawasaki disease.

Serum High Molecular Weight Adiponectin Correlates with Arterial Stiffness in Community-Dwelling Persons

Introduction. Serum high molecular weight (HMW) adiponectin, an adipocytokine, which is a protein secreted specifically by adipose tissue, improves insulin sensitivity and plays an important role in the development of metabolic syndrome and cardiovascular disease (CVD). Pulse wave velocity (PWV) is a noninvasive method of measuring arterial stiffness for the assessment of CVD in high-risk populations. We investigated whether serum HMW adiponectin is independently associated with arterial stiffness when evaluated using PWV. Methods. We randomly recruited 99 men aged 69 ± 9 (mean ± standard deviation) years and 170 women aged 68 ± 7 years during their annual health examination in a single community. Peripheral arterial stiffness was evaluated by mean PWV determined at three points: from the heart to the carotid artery, to the brachial artery, and to the ankle. Results and conclusions. Age-adjusted PWV in all sites other than the heart to the carotid artery decreased progressively with increased serum HMW adiponectin. Age-adjusted mean PWV significantly decreased from the lowest to the highest serum HMW adiponectin group. Multiple linear regression analyses for mean PWV revealed that decreased serum HMW adiponectin levels were significantly associated with increased mean PWV as well as age, BMI, SBP, DBP, prevalence of antihypertensive medication, and eGFR. Inclusion of serum HMW adiponectin into the model further increased the coefficient of determination (R2). Multivariate-adjusted mean PWV was significantly lowest in the highest serum HMW adiponectin group.

Hemoglobin is Associated with Serum High Molecular Weight Adiponectin in Japanese Community-Dwelling Persons

Serum high molecular weight (HMW) adiponectin improves insulin sensitivity, and a decreased level of serum HMW adiponectin has been reported as a risk factor for the development of diabetes and coronary heart disease. This association may be further confounded by the hemoglobin status, which is involved in the development of atherosclerosis. A cross-sectional study was carried out in 2002. Study participants, consisting of 897 men aged 61±14 (mean±standard deviation) years and 1,148 women aged 63±12 years, were randomly recruited from a single community at the time of their annual health examination. Serum HMW adiponectin levels were lowered dose-dependently with an increased hemoglobin level. Stepwise multiple linear regression analyses for serum HMW adiponectin revealed that the hemoglobin status was independently and significantly associated with serum HMW adiponectin levels as well as sex, age, body mass index (BMI), alcohol consumption, total cholesterol, triglycerides, high density lipoprotein cholesterol, antilipidemic medication, uric acid, serum gamma glutamyltransferase, and insulin resistance. Inclusion of hemoglobin levels in the model further increased the coefficient of determination. In stratified analysis, mean serum HMW adiponectin levels were significantly and similarly decreased as hemoglobin levels increased in men, ages ≥ 65 years, BMI < 23.0 kg/m(2), alcohol drinkers, and lower insulin resistance, and there were significant interactions between the two groups for BMI, alcohol consumption and insulin resistance. Hemoglobin status is inversely associated with serum HMW adiponectin levels in community-dwelling persons, especially those aged ≥ 65 years, BMI < 23.0 kg/m(2), alcohol drinkers, and lower insulin resistance groups.

Exploring the molecular mechanisms underlying the potentiation of exogenous growth hormone on alcohol-induced fatty liver diseases in mice

BackgroundGrowth hormone (GH) is an essential regulator of intrahepatic lipid metabolism by activating multiple complex hepatic signaling cascades. Here, we examined whether chronic exogenous GH administration (via gene therapy) could ameliorate liver steatosis in animal models of alcoholic fatty liver disease (AFLD) and explored the underlying molecular mechanisms.MethodsMale C57BL/6J mice were fed either an alcohol or a control liquid diet with or without GH therapy for 6 weeks. Biochemical parameters, liver histology, oxidative stress markers, and serum high molecular weight (HMW) adiponectin were measured. Quantitative real-time PCR and western blotting were also conducted to determine the underlying molecular mechanism.ResultsSerum HMW adiponectin levels were significantly higher in the GH1-treated control group than in the control group (3.98 ± 0.71 μg/mL vs. 3.07 ± 0.55 μg/mL; P < 0.001). GH1 therapy reversed HMW adiponectin levels to the normal levels in the alcohol-fed group. Alcohol feeding significantly reduced hepatic adipoR2 mRNA expression compared with that in the control group (0.71 ± 0.17 vs. 1.03 ± 0.19; P < 0.001), which was reversed by GH therapy. GH1 therapy also significantly increased the relative mRNA (1.98 ± 0.15 vs. 0.98 ± 0.15) and protein levels of SIRT1 (2.18 ± 0.37 vs. 0.99 ± 0.17) in the alcohol-fed group compared with those in the control group (both, P < 0.001). The alcohol diet decreased the phosphorylated and total protein levels of hepatic AMP-activated kinase-α (AMPKα) (phosphorylated protein: 0.40 ± 0.14 vs. 1.00 ± 0.12; total protein: 0.32 ± 0.12 vs. 1.00 ± 0.14; both, P < 0.001) and peroxisome proliferator activated receptor-α (PPARα) (phosphorylated protein: 0.30 ± 0.09 vs. 1.00 ± 0.09; total protein: 0.27 ± 0.10 vs. 1.00 ± 0.13; both, P < 0.001), which were restored by GH1 therapy. GH therapy also decreased the severity of fatty liver in alcohol-fed mice.ConclusionsGH therapy had positive effects on AFLD and may offer a promising approach to prevent or treat AFLD. These beneficial effects of GH on AFLD were achieved through the activation of the hepatic adiponectin-SIRT1-AMPK and PPARα-AMPK signaling systems.

Withdrawal of pioglitazone in patients with type 2 diabetes mellitus

The remodelling of the adipose tissue by pioglitazone may be associated with the sustained therapeutic effects. We studied the effects of withdrawal of pioglitazone after 3-month treatment on glucose, lipid and high-molecular weight (HMW) adiponectin levels as well as liver function in patients with type 2 diabetes mellitus. Forty-nine Japanese patients with type 2 diabetes mellitus were randomly assigned into the withdrawal group after 3-month treatment with pioglitazone (15 or 30 mg daily) and the non-withdrawal group. Three-month treatment with pioglitazone improved glycaemic control, homeostasis model assessment for insulin resistance (HOMA), dyslipidaemia and liver function tests in association with a marked increase in serum HMW adiponectin level. Three months later after the withdrawal of pioglitazone, however, fasting plasma glucose and HOMA increased, whereas serum HMW adiponectin decreased to the pretreatment levels. Dyslipidaemia also returned to the pretreatment level. On the other hand, liver enzymes at 3 months after the withdrawal remained lower after a mild rebound. In addition, the bone formation marker, serum bone-specific alkaline phosphatase, was significantly reduced by pioglitazone treatment in post-menopausal women. The present study suggests that 3-month treatment with pioglitazone has no sustained beneficial effects except in liver function tests in patients with type 2 diabetes mellitus.

Hepatic adiponectin receptor R2 expression is up-regulated in normal adult male mice by chronic exogenous growth hormone levels

Previous studies investigating the effects of exogenous growth hormone (GH) on the expression of adiponectin and the adiponectin receptors have generated seemingly conflicting results. Here, to determine the effects of chronic exogenous GH levels, we investigated the expression of adiponectin receptor R1 (adipoR1) in skeletal muscle and adiponectin receptor R2 (adipoR2) in the liver of normal C57BL/6 adult male mice 24 weeks after a single injection of rAAV2/1-CMV-GH1 viral particles. AdipoR1 and adipoR2 mRNA expression levels were determined by quantitative real-time reverse transcription-polymerase chain reaction. AdipoR1 and adipoR2 proteins were analyzed by Western blotting. Serum total and high molecular weight (HMW) adiponectin concentrations were measured by enzyme-linked immunosorbent assay (ELISA) kits for mice. The results demonstrated that the injection of rAAV2/1-CMV-GH1 within the concentration range of 1.0x1011 to 4.0x1011 viral particles significantly up-regulated hepatic adipoR2 gene expression. The serum HMW adiponectin level increased significantly with the concentration range of 2.0x1011 to 4.0x1011 rAAV2/1-CMV-GH1 viral particles. The injection of 4.0x1011 rAAV2/1-CMV-GH1 viral particles induced a significant increase in both serum glucose and insulin concentrations (p<0.05), and the homeostasis model assessment of insulin resistance (p<0.01). This may decrease body insulin sensitivity and therefore raise the potential risk of insulin resistance. However, exogenous GH levels did not significantly affect adipoR1 expression in skeletal muscle. In conclusion, chronic exogenous GH up-regulates hepatic adipoR2, rather than adipoR1, in vivo, and raises the serum HMW adiponectin level. However, the elevation of exogenous GH concentrations may increase the risk of insulin resistance.