Serum High Molecular Weight Adiponectin Research Articles

Metabolic, inflammatory, and oxidative stress markers in women exposed to secondhand smoke.

BackgroundSecondhand smoke (SHS) exposure has adverse effects on the cardiovascular system. This study aimed to determine the effects of SHS on the cardiovascular disease biomarkers, namely the metabolic, inflammatory, and oxidative stress markers in healthy adult women.MethodsThis comparative cross-sectional study was conducted among healthy women. The cases included those women exposed to SHS, and the controls included those women not exposed to SHS. SHS exposure was defined as being exposed to SHS for at least 15 min for 2 days per week. Venous blood was taken to measure the metabolic markers (high molecular weight adiponectin, insulin level, insulin resistance, and nonesterified fatty acids), oxidative stress markers (oxidized low density lipoprotein cholesterol and 8-isoprostane), and inflammatory markers (high-sensitivity C-reactive protein and interleukin-6). A hair nicotine analysis was also performed. An analysis of covariance and a simple linear regression analysis were conducted.ResultsThere were 101 women in the SHS exposure group and 91 women in the non-SHS exposure group. The mean (with standard deviation) of the hair nicotine levels was significantly higher in the SHS exposure group when compared to the non-SHS exposure group [0.22 (0.62) vs. 0.04 (0.11) ng/mg; P = 0.009]. No significant differences were observed in the high molecular weight adiponectin, insulin and insulin resistance, nonesterified fatty acids, 8-isoprostane, oxidized low density lipoprotein cholesterol, interleukin-6, and high-sensitivity C-reactive protein between the two groups. The serum high molecular weight adiponectin was negatively associated with the insulin level and insulin resistance in the women exposed to SHS. However, no significant relationships were seen between the high molecular weight adiponectin and nonesterified fatty acids, 8-isoprostane, oxidized low density lipoprotein cholesterol, high-sensitivity C-reactive protein in the SHS group.DiscussionThere were no significant differences in the metabolic, oxidative stress, and inflammatory markers between the SHS exposure and non-SHS exposure healthy women. A low serum level of high molecular weight adiponectin was associated with an increased insulin level and resistance in the women exposed to SHS.

ADIPONEKTIN HIGH MOLECULAR WEIGHT DAN KEKAKUAN VASKULAR DI PENYAKIT DIABETES MELITUS TIPE 2 TERKAIT GABUNGAN GLIMEPIRIDE METFORMIN DOSIS TETAP

Diabetic patients have the tendency to develop micro vascular and macro vascular complications due to the hyperglycaemic state. Thereare various types of oral hypoglycaemic agents available in Indonesia, nevertheless, these agents fail to decrease mortality and morbiditydue to the endothelial dysfunction in diabetic patients. It is not yet known whether glimepiride metformin fixed dose combination isable to improve the serum High Molecular Weight (HMW) adiponectin and vascular stiffness which are important parameters of thecardiovascular risk factors. This study was to know the effect of glimepiride metformin fixed dose combination by investigation after 12weeks of treatment towards HMW adiponectin level and vascular stiffness using ba-PWV in type 2 diabetes. This research was carried outby a Quasi experimental study with pre and post test design. The subjects were type 2 diabetes patients who came to the EndocrinologyOutpatient Clinic at the Dr. Soetomo Hospital and 6 health centres in Surabaya during December 2010 to December 2011. In this study,measuring the HMW adiponectin level in plasma was by using ELISA method and the ba-PWV by using the V Serra-1000 before and aftertreatment with glimepiride metformin fixed dose for 12 weeks. Based on the thirty five type 2 diabetic patients who met the inclusion andexclusion criteria and who were enrolled in this study, after 12 weeks of treatment, the median HMW Adiponectin level was increasedfrom 1736 ng/mL to 1770 ng/mL, which was statistically not significant (p=0.317). After 12 weeks treatment, the median of ba-PWVwas decreased from 1580 cm/sec to 1450 cm/sec, which was statistically significant (p=0.028). The level of HMW adiponectin was notsignifantly different between before and after treatment. The level of brachial ankle Pulse Wave Velocety (ba-PWV) was significantlydifferent between before and after treatment. Glimepiride metformin fixed dose combination decreases the vascular stiffness, which isone of the parameters of the endothelial dysfunction.

Serum adiponectin and insulin secretion: A direct or inverse association?

We investigated the association between serum high molecular weight (HMW) adiponectin and insulin secretion in a population‐based study, with or without adjustment for insulin sensitivity. A total of 488 participants (263 women) were included in the present study. Insulin secretion was estimated using the homeostasis model assessment of β‐cell function ± adjustment for insulin resistance using the disposition index. Multivariate analysis showed that HMW adiponectin was significantly and inversely associated with homeostasis model assessment of β‐cell function (partial regression coefficient −0.19, 95% confidence interval −0.28, −0.10, P < 0.0001). However, HMW adiponectin was significantly and positively associated with disposition index (partial regression coefficient 0.15, 95% confidence interval 0.06, 0.24, P = 0.0016). The present study showed that a positive association between HMW adiponectin levels and insulin secretion evaluated using an index incorporating adjustment for insulin resistance was identified, and vice versa using an index that did not adjust for insulin resistance.

Efficacy of probiotics on the treatment of non-alcoholic fatty liver disease

Objective: To study the clinical effect of probiotics in the treatment of non-alcoholic fatty liver disease (NAFLD). Methods: A total of 200 patients with NAFLD were randomly divided into 4 groups: control group (routine treatment group) and combined treatment group A, B and C. Each group had equal patients. The control group received orally polyene phosphatidylcholine capsules; whereas combined group A, B and C were given orally the live "combined Bifidobacterium Lactobacillus and Enterococcus powder" , "two live combined Bacillus subtilis and Enterococcus" , and the both probiotics respectively. The duration of treatment was 1 month. Laboratory parameters were evaluated before treatment and thirtieth day after treatment, including cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase (AST), fasting blood glucose (FPG), serum high molecular weight adiponectin (HMW-APN) and serum TNFα. Meanwhile the faece sample was collected for routine test and bacterial culture. Liver ultrasound scan was done in all patients. Results: In terms of blood lipids and blood glucose, each group improved after treatment with significant differences (P<0.05) except for HDL-C. As for liver function, serum ALT and AST decreased after treatment in each group; especially in combined group C which were lower than those of control group [(33.7±7.6) U/L vs. (45.0±8.5) U/L; (22.0±1.6) U/L vs. (29.4±3.7) U/L; P<0.05]. TNFα levels decreased after treatment in each group, in addition the values in combined group C was significantly lower than that of control group[(0.51±0.27) µg/L vs. (0.82±0.28) µg/L, P<0.05]. Serum HMW-APN increased after treatment in each group, and the HMW-APN in combined C group was significantly higher than that of control group[(9.28±3.72) µg/L vs. (7.87±3.96)µg/L, P<0.05]. (5) After treatment, all groups showed improvement of fatty liver by ultrasound, but the difference between groups was not statistically significant. (6) Compared with before treatment, fecal flora in combined groups was all reduced (P<0.01), but it was comparable before and after treatment in control group. Conclusions: Probiotics improve intestinal microecological system in NAFLD patients via inhibiting TNFα and enhancing adiponectin, possibly resulting in regulating blood glucose, lipid metabolism, and protecting liver injury from NAFLD.

High Dietary ω-6:ω-3 PUFA Ratio Is Positively Associated with Excessive Adiposity and Waist Circumference

Objective: The aim of this study was to analyze dietary ω-6:ω-3 polyunsaturated fatty acid (PUFA) ratio and its association with adiposity and serum adiponectin levels in a Mexican population. Methods: In this cross-sectional study, individuals with a BMI ≥ 18.5 kg/m², were classified using four methods to measure adiposity. Parameters of body composition were measured by InBody 3.0. Diet intake was evaluated prospectively using a 3-day written food record. Serum high-molecular weight adiponectin isoform was measured using an ELISA assay. Biochemical and adiposity variables were analyzed by tertiles of dietary ω-6:ω-3 PUFA ratio. Results: A total of 170 subjects were recruited with a mean age of 36.9 ± 11.8 years. The 73.5% of subjects were women. Subjects in the higher tertile of dietary ω-6:ω-3 PUFA ratio had more adiposity and higher levels of triglycerides, VLDL-c, glucose, insulin and HOMA-IR than those in the first tertile (p < 0.05). Adiponectin levels showed a trend according to dietary ω-6:ω-3 PUFA ratio (p = 0.06). A linear regression model showed that waist circumference, insulin, and HOMA-IR have positive associations with dietary ω-6:ω-3 PUFA ratio. Conclusion: This study suggests that high dietary ω-6:ω-3 PUFA ratio is positively associated with excessive adiposity and worse metabolic profile.

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.

Characteristics of hepatic insulin-sensitive nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) plays a crucial role in type 2 diabetes and hepatocellular carcinoma. The major underlying pathogenesis is hepatic insulin resistance. The aim of the present study was to characterize patients with NAFLD with paradoxically normal hepatic insulin sensitivity relative to patients with NAFLD with hepatic insulin resistance. We recruited 26 patients with NAFLD and divided them into three groups ranked by the level of hepatic insulin sensitivity (HIS; high‐HIS, mid‐HIS, low‐HIS), as assessed by the hyperinsulinemic‐euglycemic clamp studies using stable isotope. Hepatic insulin sensitivity of the high‐HIS group was identical to that of the non‐NAFLD lean control (clamped percent suppression of endogenous glucose production, 91.1% ± 5.2% versus 91.0% ± 8.5%, respectively) and was significantly higher than that of the low‐HIS group (66.6% ± 7.5%; P < 0.01). Adiposity (subcutaneous, visceral, intrahepatic, and muscular lipid content), hepatic histopathology, and expression levels of various genes by using liver biopsies, muscle, and adipose tissue insulin sensitivity, plasma metabolites by metabolomics analysis, putative biomarkers, and lifestyles were assessed and compared between the high‐HIS and low‐HIS groups. Among these, adipose tissue insulin sensitivity assessed by clamped percent suppression of free fatty acid, serum high molecular weight adiponectin, and plasma tricarboxylic acid cycle metabolites, such as citric acid and cis‐aconitic acid, were significantly higher in the high‐HIS group compared to the low‐HIS group. In contrast, there were no differences in adiposity, including intrahepatic lipid content assessed by proton magnetic resonance spectroscopy (28.3% ± 16.1% versus 20.4% ± 9.9%, respectively), hepatic histopathology, other putative biomarkers, and lifestyles. Conclusion: High levels of adipose tissue insulin sensitivity, serum high molecular weight adiponectin, and plasma tricarboxylic acid cycle metabolites are unique characteristics that define patients with hepatic insulin‐sensitive NAFLD regardless of intrahepatic lipid content. (Hepatology Communications 2017;1:634–647)

Metabolomics allows the discrimination of the pathophysiological relevance of hyperinsulinism in obese prepubertal children.

Insulin resistance (IR) is the cornerstone of the obesity-associated metabolic derangements observed in obese children. Targeted metabolomics was employed to explore the pathophysiological relevance of hyperinsulinemia in childhood obesity in order to identify biomarkers of IR with potential clinical application. One hundred prepubertal obese children (50 girls/50 boys, 50% IR and 50% non-IR in each group), underwent an oral glucose tolerance test for usual carbohydrate and lipid metabolism determinations. Fasting serum leptin, total and high molecular weight-adiponectin and high-sensitivity C-reactive protein (CRP) levels were measured and the metabolites showing significant differences between IR and non-IR groups in a previous metabolomics study were quantified. Enrichment of metabolic pathways (quantitative enrichment analysis) and the correlations between lipid and carbohydrate metabolism parameters, adipokines and serum metabolites were investigated, with their discriminatory capacity being evaluated by receiver operating characteristic (ROC) analysis. Twenty-three metabolite sets were enriched in the serum metabolome of IR obese children (P<0.05, false discovery rate (FDR)<5%). The urea cycle, alanine metabolism and glucose-alanine cycle were the most significantly enriched pathways (PFDR<0.00005). The high correlation between metabolites related to fatty acid oxidation and amino acids (mainly branched chain and aromatic amino acids) pointed to the possible contribution of mitochondrial dysfunction in IR. The degree of body mass index-standard deviation score (BMI-SDS) excess did not correlate with any of the metabolomic components studied. In the ROC analysis, the combination of leptin and alanine showed a high IR discrimination value in the whole cohort (area under curve, AUCALL=0.87), as well as in boys (AUCM=0.84) and girls (AUCF=0.91) when considered separately. However, the specific metabolite/adipokine combinations with highest sensitivity were different between the sexes. Combined sets of metabolic, adipokine and metabolomic parameters can identify pathophysiological relevant IR in a single fasting sample, suggesting a potential application of metabolomic analysis in clinical practice to better identify children at risk without using invasive protocols.

Serum C-peptide, Total and High Molecular Weight Adiponectin, and Pancreatic Cancer: Do Associations Differ by Smoking?

Background: Studies examining associations between circulating concentrations of C-peptide and total adiponectin, two biomarkers related to obesity and insulin secretion and sensitivity and pancreatic ductal adenocarcinoma (PDA) risk have shown inconsistent results and included limited numbers of smokers.Methods: We examined associations of these biomarkers and high molecular weight (HMW) adiponectin with PDA, overall, and by smoking status. We conducted a pooled nested case-control analysis in 3 cohorts (Prostate, Lung, Colorectal, and Ovarian Cancer Trial, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and Cancer Prevention Study-II), with 758 cases (435 current smokers) and 1,052 controls (531 smokers) matched by cohort, age, sex, race, blood draw date and follow-up time. We used conditional logistic regression adjusted for age, smoking, diabetes, and body mass index to calculate ORs and 95% confidence intervals (CI).Results: Circulating C-peptide concentration was not associated with PDA in never or former smokers, but was inversely associated with PDA in current smokers (per SD OR = 0.67; 95% CI, 0.54-0.84; Pinteraction = 0.005). HMW adiponectin was inversely associated with PDA in never smokers (OR = 0.43; 95% CI, 0.23-0.81), not associated in former smokers, and positively associated in smokers (OR = 1.23; 95% CI, 1.04-1.45; Pinteraction = 0.009). Total adiponectin was not associated with PDA in nonsmokers or current smokers.Conclusions: Associations of biomarkers of insulin secretion and sensitivity with PDA differ by smoking status. Smoking-induced pancreatic damage may explain the associations in smokers while mechanisms related to insulin resistance associations in nonsmokers.Impact: Future studies of these biomarkers and PDA should examine results by smoking status. Cancer Epidemiol Biomarkers Prev; 26(6); 914-22. ©2017 AACR.

Repeatability of Oral Sugar Test Results, Glucagon-Like Peptide-1 Measurements, and Serum High-Molecular-Weight Adiponectin Concentrations in Horses.

BackgroundRepeatability of the oral sugar test (OST) has not been evaluated.ObjectivesWe hypothesized that OST glucose, insulin, active (aGLP‐1) and total (tGLP‐1) glucagon‐like peptide 1, and high‐molecular‐weight (HMW) adiponectin results would be repeatable.AnimalsFifty‐three horses from a Tennessee research facility (n = 23) and private practice in Missouri (n = 30), including animals with medical histories of equine metabolic syndrome.MethodsTwo OSTs were performed 7–14 days apart and plasma glucose and insulin concentrations were measured at 0, 60, and 75 minutes; a positive result was defined as detection of an insulin concentration >45 μU/mL at 60 or 75 minutes. Plasma aGLP‐1 and serum tGLP‐1 concentrations at 75 minutes and serum HMW adiponectin concentrations at 0 minute were measured in the Missouri group. Bland‐Altman analyses were performed.ResultsNo adverse events were reported. Bland‐Altman analysis indicated mean ± SD bias of 1.5 ± 14.8 μU/mL (95% confidence interval [CI], −27.6 to 30.5 μU/mL) and 1.2 ± 16.1 μU/mL (95% CI, −30.4 to 32.8 μU/mL) for insulin concentrations at 60 and 75 minutes, respectively. There was 91 and 83% agreement in test interpretation between test days for OST insulin results for all horses in the Tennessee and Missouri groups, respectively.Conclusions and Clinical ImportanceRepeatability of the OST was acceptable when values obtained from Bland‐Altman analyses were evaluated, and there was good agreement in binary (negative/positive) test interpretation for insulin concentrations. However, wide 95% CIs were detected for insulin concentrations.

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 Resistin Level and Progression of Atherosclerosis during Glucocorticoid Therapy for Systemic Autoimmune Diseases.

Adipokines are important regulators of several processes, including inflammation and atherosclerosis. In patients with systemic autoimmune diseases, atherosclerosis is accelerated with higher cardiovascular morbidity and mortality. We prospectively investigated the association of adipokines and glucocorticoid therapy with progression of premature atherosclerosis in 38 patients starting glucocorticoid therapy for systemic autoimmune diseases. To detect premature atherosclerosis, carotid ultrasonography was performed at initiation of glucocorticoid therapy and after a mean three-year follow-up period. The ankle-brachial pressure index and cardio-ankle vascular index (CAVI) were measured. Serum adipokine levels were determined with enzyme-linked immunosorbent assay kits. Twenty-three patients (60.5%) had carotid artery plaque at baseline. The carotid artery intima-media thickness (IMT) increased significantly during follow-up. Glucocorticoids reduced the serum resistin level, while increasing serum leptin and high molecular weight-adiponectin. There was slower progression of atherosclerosis (carotid IMT and CAVI) at follow-up in patients with greater reduction of serum resistin and with higher cumulative prednisolone dose. In conclusion, progression of premature atherosclerosis occurred at an early stage of systemic autoimmune diseases before initiation of glucocorticoid therapy. Since resistin, an inflammation and atherosclerosis related adipokine, is reduced by glucocorticoids, glucocortidoid therapy may not accelerate atherosclerosis in patients with systemic autoimmune diseases.

Changes in Serum High-Molecular-Weight Adiponectin Levels in Critically Ill Children with Systemic Inflammatory Response Syndrome

Background: The aim of the study was to evaluate the effect of the systemic inflammatory response syndrome (SIRS) on serum high-molecular-weight adiponectin (HMWA) levels. Method: Twelve children with SIRS were enrolled in this study at the intensive care unit (ICU). Twelve age and sex matched healthy subjects were selected as controls. Serum HMWA, interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) levels were determined after 2 hours and 24 hours, and on the day of discharge which was on the average 9.4 days after ICU admission. Results: 2 hours after admission to the ICU, the patients had significantly decreased serum HMWA levels compared with healthy controls (P &lt; .001). 24 hours after the admission, the patients did not have any significant changes in their HMWA levels, however on the day of discharge, on average 9.4 days after hospital admission, a significant increase was observed (P &lt; .05). After the treatment, there was a decrease in serum PCT, IL-6 and CRP levels. The only variable that was decreased 24 hours after the ICU admission was PCT (P &lt; .05). A negative correlation was found between serum HMWA and PCT levels, and between HMWA and CRP (P &lt; .05 and P &lt; .01), however no correlation was found between HMWA and IL-6. Conclusion: In SIRS we observed a marked reduction in serum HMWA concentrations and a profound increase in IL-6, PCT, and CRP levels. A significant relationship between serum HMWA and PCR and CRP levels was evident.

Fetuin-A, adiposity-linked insulin resistance and responsiveness to an educational-based weight excess reduction program: a population-based survey in prepubertal schoolchildren.

The secreted hepatokine fetuin-A emerges as an independent predictor of type 2 diabetes in adulthood. The overall aims of this study were: (1) to investigate the associations of fetuin-A with adiposity and insulin resistance, as well as its relationship with adipokines, in prepubertal children, and, (2) to evaluate whether, in prepubertal obesity, serum fetuin-A levels may either change or predict the responsiveness to an educational-based weight excess reduction program. We studied 200 prepubertal children (boys/girls: 89/111; Tanner stage 1; age: 5-13 years), included in a cohort of 44,231 adolescents who participated in an extensive Italian school-based survey. According to Cole's criteria, 100 individuals were lean (boys/girls: 57/43) and 100 obese (boys/girls: 54/46). A subset of 53 obese individuals (boys/girls: 28/25; age: 6-12 years) were also evaluated after a weight excess reduction program. Serum fetuin-A, leptin, total and high molecular weight adiponectin levels, as well as homeostasis model assessment of insulin resistance were assessed. When compared with lean, obese children exhibited higher ( p < 0.0001) fetuin-A concentrations, without differences between sex. Fetuin-A was positively associated with adiposity, homeostasis model assessment of insulin resistance, and leptin levels. In multivariate analysis, the associations between fetuin-A and leptin or homeostasis model assessment of insulin resistance lost the significance after adjustment for BMI Z-score, which, in turn, represented an independent determinant of fetuin-A (R 2adj 0.327; p < 0.0001). Notably, after weight excess reduction program, fetuin-A levels dropped ( p < 0.0001 vs. basal). Interestingly, no significant differences of fetuin-A concentrations between responders and no responders were found. In prepubertal children, fetuin-A represents an early marker of adiposity, and its reduction after lifestyle intervention may partly contribute to the beneficial effects of weight excess reduction program.

Effects of Delayed Sample Processing on Determination of Total and High Molecular Weight (HMW) Adiponectin in Serum and Plasma: A Pilot Study

&lt;p&gt;Adiponectin is a beneficial adipocyte-secreted hormone, which circulates in a variety of multimeric forms termed low and high molecular weight (LMW/HMW). Effectiveness of clinical therapeutic trials which target adiponectin rely on accurate determination of circulating total and HMW adiponectin levels but the accuracy may be influenced by variations in sample handling processes. The aim of this pilot study was to investigate the effects of delayed processing of blood samples on the concentration of total and HMW adiponectin.&lt;/p&gt;&lt;p&gt;Materials and Methods: Fasting blood samples were collected for analysis of total and HMW adiponectin concentrations in EDTA plasma and serum from eight healthy participants. Samples were centrifuged post 15 min storage at 4&lt;sup&gt;o&lt;/sup&gt;C as the comparative ‘ideal’ method or after up to 72 h of refrigerated storage or 6 h at room temperature. Total and HMW adiponectin concentrations were measured by ELISA.&lt;/p&gt;&lt;p&gt;Results: Under ideal handling conditions measurements of total and HMW adiponectin concentrations were significantly higher in serum than in plasma (mean difference: -1.3 µg/mL [95% CI: -1.6, -1.0], p&amp;lt;0.001; and, -0.6 µg/mL [95% CI: -0.7, -0.5], p&amp;lt;0.001, respectively). Storage of blood samples at 4&lt;sup&gt;o&lt;/sup&gt;C for 72 h resulted in significant reductions in concentration of total adiponectin in serum (mean difference: -1.4 µg/mL [95% CI: -2.0, -0.8], p=0.001) and HMW adiponectin in plasma (mean difference: -0.6 µg/mL [95%CI: -0.9, -0.2], p=0.007), compared with ideal conditions. Further analysis of serum samples showed a significant decrease in total adiponectin concentration after 6 h storage at 4&lt;sup&gt;o&lt;/sup&gt;C (mean difference: -1.4 µg/mL [95% CI: -2.0, -0.8], p=0.001) compared with ideal conditions.&lt;/p&gt;&lt;p&gt;Conclusions: Delayed processing of samples may have differential effects on the concentration of total and HMW adiponectin in serum or plasma. Larger studies are warranted for clinical intervention trials.&lt;/p&gt;

Androgen and metabolic changes after orchiectomy

Bilateral orchiectomy reduces serum testosterone, an androgen stimulating the growth and proliferation of both normal and malignant prostate cancer cells. Low testosterone concentrations are associated with obesity, insulin resistance and an adverse lipid profile in men. The aim of this study was to measure the influence of post-orchiectomy changes in serum androgen concentrations on markers for metabolic syndrome. Fasting venous blood samples were obtained at baseline, 3-hourly (1-12 hours) and weekly (1-4 weeks) intervals post-orchiectomy from 10 patients (mean age 73.45 ± 12.7 years) with prostate carcinoma and high serum prostate-specific antigen (PSA) concentrations. Serum testosterone, free testosterone, PSA, insulin, luteinising hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate(DHEA-S) and glucose concentrations were measured. Serum high molecular weight adiponectin (HMW-A) concentrations and insulin resistance were determined. Baseline waist circumference and weight were compared to values obtained after 4 weeks. For median difference of paired data, 95% confidence intervals (CI) were calculated to measure the significance of differences between baseline and post-orchiectomy results. Compared to baseline, serum concentrations of testoterone, free testosterone, PSA and DHEA-S decreased, and LH, FSH, insulin and insulin resistance increased significantly at different times post-orchiectomy. HMW-A was significantly decreased at 9 and 12 hours and then gradually increased. Serum glucose concentrations remained unchanged. Median weight and waist circumference increased by 3.5 kg and 5 cm, respectively, within 4 weeks. Post-orchiectomy hormonal changes resemble those found in metabolic syndrome.

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.

Intravenous Mycobacterium Bovis Bacillus Calmette-Guérin Ameliorates Nonalcoholic Fatty Liver Disease in Obese, Diabetic ob/ob Mice

Inflammation and immune response profoundly influence metabolic syndrome and fatty acid metabolism. To analyze influence of systemic inflammatory response to metabolic syndrome, we inoculated an attenuated vaccine strain of Mycobacterium bovis Bacillus Calmette–Guérin (BCG) into leptin-deficient ob/ob mice. BCG administration significantly decreased epididymal white adipose tissue weight, serum insulin levels, and a homeostasis model assessment of insulin resistance. Serum high molecular weight (HMW) adiponectin level and HMW/total adiponectin ratio of the BCG treated mice were significantly higher than those of control mice. Hepatic triglyceride accumulation and macrovesicular steatosis were markedly alleviated, and the enzymatic activities and mRNA levels of lipogenic-related genes in liver were significantly decreased in the BCG injected mice. We also exposed human hepatocellular carcinoma HepG2 cells to high levels of palmitate, which enhanced endoplasmic reticulum stress-related gene expression and impaired insulin-stimulated Akt phosphorylation (Ser473). BCG treatment ameliorated both of these detrimental events. The present study therefore suggested that BCG administration suppressed development of nonalcoholic fatty liver disease, at least partly, by alleviating fatty acid-induced insulin resistance in the liver.