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PubMed2006

Adiponectin is an important determinant of apoA-I catabolism.

OBJECTIVE: Plasma concentration of adiponectin is positively correlated with high-density lipoprotein (HDL) cholesterol level. However, the role of adiponectin on HDL metabolism remains unknown. This prompted us to perform an in vivo kinetic study of apoA-I, the main apolipoprotein of HDL, using stable isotopes, in 22 subjects with a wide range of plasma adiponectin, including 11 patients with metabolic syndrome (8 with type 2 diabetes, 3 without type 2 diabetes) and 11 normal individuals. METHODS AND RESULTS: In the 22 studied subjects, plasma adiponectin levels ranged from 2.57 to 14.44 microg/mL and apoA-I fractional catabolic rate (FCR) values ranged from 0.142 to 0.340 day(-1). A strong negative correlation was found between adiponectin and apoA-I FCR (r=-0.66, P<0.001) in the whole studied population and, to a similar extent, in patients with metabolic syndrome (r=-0.73, P=0.010) and normal subjects (r=-0.68, P=0.020), separately. In multivariable analysis, apoA-I FCR was associated negatively with adiponectin (P=0.005) and positively with HDL triglycerides/cholesterol ratio (P=0.006), but not with age, sex, body mass index (BMI), waist circumference, plasma triglycerides, HDL cholesterol, fasting glycemia, and QUICKI. Both adiponectin and HDL triglycerides/cholesterol ratio explained 62% of the variance of apoA-I FCR and adiponectin on its own explained 43%. CONCLUSIONS: Our kinetic study shows a strong negative correlation between adiponectin and apoA-I FCR, which can explain the positive link between HDL cholesterol and adiponectin. This association is independent of obesity, insulin resistance, and the content of triglycerides within HDL particles. These data suggest that adiponectin may have a direct role on HDL catabolism.

Adiponectin↗
PubMed2004

Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages.

BACKGROUND: Vascular inflammation and subsequent matrix degradation play an important role in the development of atherosclerosis. We previously reported that adiponectin, an adipose-specific plasma protein, accumulated to the injured artery and attenuated vascular inflammatory response. Clinically, high plasma adiponectin level was associated with low cardiovascular event rate in patients with chronic renal failure. The present study was designed to elucidate the effects of adiponectin on matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in human monocyte-derived macrophages. METHODS AND RESULTS: Human monocyte-derived macrophages were incubated with the physiological concentrations of human recombinant adiponectin for the time indicated. Adiponectin treatment dose-dependently increased TIMP-1 mRNA levels without affecting MMP-9 mRNA levels. Adiponectin also augmented TIMP-1 secretion into the media, whereas MMP-9 secretion and activity were unchanged. Time course experiments indicated that TIMP-1 mRNA levels started to increase at 24 hours of adiponectin treatment and were significantly elevated at 48 hours. Adiponectin significantly increased interleukin-10 (IL-10) mRNA expression at the transcriptional level within 6 hours and significantly increased IL-10 protein secretion within 24 hours. Cotreatment of adiponectin with anti-IL-10 monoclonal antibody completely abolished adiponectin-induced TIMP-1 mRNA expression. CONCLUSIONS: Adiponectin selectively increased TIMP-1 expression in human monocyte-derived macrophages through IL-10 induction. This study identified, for the first time, the adiponectin/IL-10 interaction against vascular inflammation.

Adiponectin↗
PubMed2006

Adiponectin replenishment ameliorates obesity-related hypertension.

Patients with obesity are susceptible to hypertension. We have reported that the plasma adiponectin levels are decreased in obesity and that adiponectin has many defensive properties against obesity-related diseases, such as type 2 diabetes and coronary artery disease. The aim of this study was to determine the relationship between adiponectin and hypertension in mice. We measured blood pressure and heart rate directly by a catheter in the carotid artery and indirectly by automatic sphygmomanometer at the tail artery. Obese KKAy mice had significantly lower plasma adiponectin levels and higher systolic blood pressure than control C57BL/6J mice at 21 weeks of age. Adenovirus-delivered adiponectin significantly decreased blood pressure in KKAy mice. The direct role of adiponectin on blood pressure regulation under insulin resistance-free state was investigated in adiponectin-knockout (KO) mice. Adiponectin KO mice developed hypertension when maintained on a high-salt diet (8% NaCl) without insulin resistance. The hypertension of salt-fed adiponectin KO mice was associated with reduced mRNA levels of endothelial NO synthase (eNOS) and prostaglandin I(2) synthase in aorta and low metabolite levels of endothelial NO synthase and prostaglandin I(2) synthase in plasma. Adiponectin therapy lowered the elevated blood pressure and corrected the above mRNA levels to those of the wild type. Our results suggest that hypoadiponectinemia contributes to the development of obesity-related hypertension, at least in part, directly, in addition to its effect via insulin resistance, and that adiponectin therapy can be potentially useful for hypertension in patients with the metabolic syndrome.

Adenoviridae↗
PubMed2005

Adiponectin inhibits endothelial synthesis of interleukin-8.

Adiponectin is an antiatherogenic adipokine that inhibits inflammation by mechanisms that are not completely understood. We explored the effect of adiponectin on endothelial synthesis of interleukin-8 (IL-8), a pro-inflammatory chemokine that plays a role in atherogenesis. Adiponectin decreased the secretion of IL-8 from human aortic endothelial cells (HAEC) stimulated with tumor necrosis factor-alpha (TNF-alpha). Adiponectin also inhibited IL-8 mRNA expression induced by TNF-alpha. Phosphorylation of IkappaB-alpha was decreased by adiponectin, but phosphorylation of ERK, SAPK/JNK, and p38MAPK were unaffected. Adiponectin increased intra-cellular cAMP levels in HAEC in a dose-dependent manner; PKA activity was also increased. The inhibitory effect of adiponectin on TNF-alpha-induced IL-8 synthesis was inhibited by pretreatment with Rp-cAMP, a PKA inhibitor. These observations suggest that adiponectin inhibits IL-8 synthesis through inhibition of a PKA dependent NF-kappaB signaling pathway. We also showed that adiponectin enhances Akt phosphorylation. The inhibitory effect of adiponectin on TNF-alpha-induced IL-8 synthesis was abrogated in part by pretreatment with the PI3 kinase inhibitor LY294002 or by Akt siRNA transfection, suggesting that Akt activation might inhibit IL-8 synthesis induced by TNF-alpha. We conclude that inhibition of NF-kappaB and activation of Akt phosphorylation may mediate adiponectin inhibition of atherosclerosis.

Adenylate Kinase↗
PubMed2006

A novel enzyme-linked immunosorbent assay specific for high-molecular-weight adiponectin.

Human plasma contains at least three forms of adiponectin: a trimer, a hexamer, and a high-molecular-weight (HMW) multimer. We purified HMW adiponectin from human plasma using its affinity to gelatin and obtained monoclonal antibodies against it. On Western blot analysis, the reactivity of these monoclonal antibodies was shown to be restricted to a non-heat-denatured form of adiponectin molecules. On heating, the collagen-like domain of adiponectin molecules became denatured, and thus the trimer form could not be maintained. From these, monoclonal antibodies against HMW adiponectin were suggested to react with the intact trimer of adiponectin. With these monoclonal antibodies, we developed a sandwich ELISA system for quantifying adiponectin in human serum. Its specificity was verified by analysis of serum fractions separated by gel-filtration chromatography, and our ELISA system was found to be HMW adiponectin-specific. With this novel ELISA, the HMW adiponectin concentrations were 8.4 +/- 5.5 microg/ml (mean +/- SD) in healthy women and 6.2 +/- 3.6 microg/ml in healthy men. Also, serum with a lower HMW adiponectin concentration was shown to have a lower HMW ratio (i.e., HMW adiponectin/total adiponectin).

Adiponectin↗
PubMed2005

Adiponectin is inversely associated with renal function in type 1 diabetic patients.

OBJECTIVE: Adipose tissue is a source of several adipocytokines that may contribute to vascular complications. We examined the relation of adiponectin with several cardiovascular risk factors and with micro- and macrovascular outcomes in type 1 diabetic patients. DESIGN: Cross-sectional data on 543 type 1 diabetic patients from the EURODIAB Prospective Complications Study were analyzed. We determined adiponectin, TNF-alpha, IL-6, C-reactive protein, soluble vascular cell adhesion molecule (sVCAM-1), and sE-selectin by ELISA. RESULTS: We found that adiponectin was negatively correlated with body mass index, waist to hip ratio, insulin, and fasting triglyceride, and positively with high-density lipoprotein, low-density lipoprotein, and total cholesterol, TNF-alpha, and sVCAM-1, but was not related to C-reactive protein, IL-6, and sE-selectin. Surprisingly, significantly raised concentrations of adiponectin were found with albuminuria, retinopathy, and cardiovascular diseases (for all, P < 0.0001). Adiponectin levels were inversely associated with glomerular filtration rate (GFR) (P < 0.0001). Multivariate regression models showed that the associations of adiponectin with albuminuria and GFR were independent of established risk factors. The association between adiponectin and albuminuria was attenuated by GFR, whereas the association of adiponectin with retinopathy and cardiovascular disease disappeared after adjustments for established risk factors. The association of adiponectin with sVCAM-1 was independent of established risk factors. CONCLUSION: We conclude that in type 1 diabetic patients, adiponectin is associated with impaired renal function. Adiponectin may be enhanced in type 1 diabetic patients as a physiological counterregulatory response to mitigate endothelial damage and vascular damage.

Adiponectin↗
PubMed2006

Adiponectin and mortality in patients undergoing coronary angiography.

CONTEXT: The adipokine adiponectin has been suggested to protect against coronary artery disease (CAD). However, studies addressing the association between adiponectin and mortality are sparse. OBJECTIVE: The objective of the study was to elucidate the relationship between adiponectin and mortality. DESIGN, SETTING, AND PARTICIPANTS: Adiponectin was determined in 2473 persons with and 673 persons without angiographic CAD. During a mean follow-up period of 5.45 yr, 427 persons with CAD and 55 persons without CAD died. MAIN OUTCOME MEASURE: Hazard ratios for mortality according to adiponectin levels were measured. RESULTS: Adiponectin was positively related to female gender, age, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, homocysteine, and N-terminal pro-B-type natriuretic peptide. It was inversely related to glomerular filtration rate, body mass index, and triglycerides and was low in diabetes mellitus and CAD. An increase of 1 sd in adiponectin was associated with unadjusted and fully adjusted hazard ratios for death from any cause of 1.31 [95% confidence interval (CI) 1.20-1.42] and 1.22 (95% CI 1.12-1.34), and for death from cardiovascular causes of 1.32 (95% CI 1.19-1.45) and 1.23 (95% CI 1.11-1.37), respectively. In angiographic CAD, stable CAD, and unstable CAD, the predictive value of adiponectin was similar to that in the entire cohort, but it did not attain statistical significance in persons without angiographic CAD. Adiponectin was also positively related to the risk of death from noncardiovascular causes. CONCLUSIONS: Despite the common view about adiponectin as a protective molecule in cardiovascular disease, high adiponectin independently predicts all-cause, cardiovascular, and noncardiovascular mortality in individuals with CAD.

Adiponectin↗
PubMed2006

Decreased total and high molecular weight adiponectin are independent risk factors for the development of type 2 diabetes in Japanese-Americans.

CONTEXT: Adiponectin is a hormone secreted by adipocytes that acts as an antidiabetic adipokine. Adiponectin exists as multimers in plasma, and high molecular weight (HMW) adiponectin is particularly thought to be the active form of the protein. OBJECTIVE: The aim of the study was to assess whether decreased total and HMW adiponectin are independent risk factors for the development of type 2 diabetes. DESIGN: Study subjects were Japanese-Americans enrolled in the Hawaii-Los Angeles-Hiroshima study between 1992 and 2002. Duration of follow-up was an average of 5.4 yr. PARTICIPANTS: We investigated 321 men and 445 women who were nondiabetic Japanese-Americans. Glucose tolerance was evaluated according to 1997 American Diabetes Association criteria, and 112 subjects developed type 2 diabetes during the follow-up period. MAIN OUTCOME MEASURE: The influence of baseline total and HMW adiponectin on the development of type 2 diabetes was the main outcome measure. RESULTS: Subjects who developed type 2 diabetes had significantly decreased plasma total and HMW adiponectin compared with those who did not develop the disease (P < 0.001, respectively). In a Cox proportional hazards model, both decreased total and HMW adiponectin levels were independent risk factors for the progression to type 2 diabetes after adjusting for sex, age, body mass index, waist-to-hip ratio, homeostasis model assessment, and classification of 75-g glucose tolerance test (hazards ratio: total, 0.600, P = 0.018; HMW, 0.614, P = 0.001, respectively). Dividing tertiles of adiponectin, hazards ratios in the lowest vs. highest tertile were total, 1.787 (95% confidence interval, 1.006-3.173); and HMW, 2.493 (95% confidence interval, 1.342-4.632), after similar adjustments. CONCLUSIONS: Decreased total adiponectin is an independent risk factor for the progression to type 2 diabetes in Japanese-Americans. Moreover, HMW adiponectin more closely associates with the progression to type 2 diabetes when compared with total adiponectin.

Adiponectin↗
PubMed2004

Effect of glucocorticoids on adiponectin: a study in healthy subjects and in Cushing's syndrome.

OBJECTIVE: Glucocorticoids were found to inhibit adiponectin gene expression and secretion both in vitro and in animal models. We evaluated first the acute effect of i.v. glucocorticoids on adiponectin in normal subjects and secondly plasma adiponectin levels in a series of patients with Cushing's syndrome compared with controls. DESIGN AND METHODS: Hydrocortisone (25 mg) was administered i.v. to five healthy volunteers, with blood samples taken at -15, 0, 30, 60, 120 and 180 min. Twenty-one patients with Cushing's syndrome were divided in two groups: one with 11 obese and the other with 10 non-obese Cushing's patients. Each group was compared with controls that were matched for sex, age, body mass index, waist circumference, glucose, insulin, lipid levels and blood pressure. RESULTS: In normal subjects, hydrocortisone produced a decrease in adiponectin at 30 and 60 min, compared with placebo (P<0.05). Adiponectin was lower in non-obese Cushing's patients than in non-obese controls (P<0.004). In contrast, there was no difference in adiponectin levels in obese Cushing's patients and in obese controls. Adiponectin was inversely correlated (P<0.05) with homeostasis model assessment index in both obese and non-obese Cushing's patients; in non-obese Cushing's patients only, adiponectin was inversely correlated with urinary cortisol (P<0.05). CONCLUSIONS: Glucocorticoids inhibit adiponectin in man, as shown by both exogenous administration to healthy subjects and endogenous cortisol hyperproduction. Similar levels of adiponectin in obese Cushing's patients and their obese controls indicate that obesity per se may act as a predominant factor in masking the relationship between adiponectin and cortisol.

Adiponectin↗
PubMed2004

Serum adiponectin concentrations in relation to maternal and perinatal characteristics in newborns.

OBJECTIVE: To assess serum adiponectin levels of neonates in relation to ponderal index and birth length with and without adjustment for potential confounding factors including maternal factors and perinatal characteristics. DESIGN: A cross-sectional study. METHODS: Three hundred and three newborns (Caucasian, singleton, full term, with a birth weight of > or =2500 g, and apparently healthy) were included in the study. Blood samples were collected from the newborns no later than the fifth day of life for measurements of adiponectin and major IGF system components (IGF-I, IGF-II, IGF binding protein-3 (IGFBP-3)). The data were analyzed using simple and multiple regression analyses. RESULTS: Adiponectin is substantially higher in neonates than in adults, with no evidence of the gender dimorphism observed among adults. We found an inverse association between neonatal adiponectin levels and newborn ponderal index and a positive association with newborn length by univariate analysis. We also found a statistically significant inverse association of adiponectin with jaundice/bilirubin, and a marginally significant positive association of this hormone with IGFBP-3 but no significant association with any maternal factors. In multivariate analysis, the inverse association between serum adiponectin and ponderal index does not remain significant after adjustment for potential confounding factors. In contrast, neonatal adiponectin levels correlate inversely significantly and independently with liver maturity and IGF-II and tend to remain positively associated with IGFBP-3 and increased birth length. CONCLUSIONS: An inverse association of adiponectin with ponderal index by univariate analysis is not independent from confounding factors. In contrast, the positive association between serum adiponectin and birth length may reflect either a direct effect of adiponectin or an adiponectin-mediated increase in the sensitivity of tissues to insulin and components of the IGF system, and needs to be explored further.

Adiponectin↗
PubMed2006

Serum adiponectin and leptin levels in relation to the metabolic syndrome, androgenic profile and somatotropic axis in healthy non-diabetic elderly men.

OBJECTIVE: The relationships between adipocytokines, sex steroids and the GH/IGF-I axis is poorly studied and subject to controversy in healthy elderly male subjects. We investigated the association between both adiponectin and leptin, and the metabolic syndrome (MetS), lipid parameters, insulin sensitivity, sex steroids and IGF-I in healthy non-diabetic Lebanese men. DESIGN AND METHODS: In this cross-sectional study, a total of 153 healthy non-diabetic men aged 50 and above (mean age 59.3 +/- 7 years) had a detailed clinical and biological evaluation. Subjects were classified according to the National Cholesterol Education Program criteria of the MetS. Insulin sensitivity was determined by the Quantitative Insulin Sensitivity Check Index (QUICKI). RESULTS: Subjects with the MetS had lower adiponectin and higher leptin levels (P < 0.0001 for both variables) compared with individuals without the MetS. Adiponectin was significantly correlated with waist size, triglycerides, high-density lipoprotein (HDL) cholesterol and QUICKI (r = -0.33, -0.26, 0.45 and 0.36 respectively, P < 0.0001 for all variables). The relation between adiponectin and HDL cholesterol, triglycerides and QUICKI remained significant after adjustment for age and body mass index (BMI). Also, leptin was strongly correlated with waist size and QUICKI (r = 0.63 and -0.63 respectively, P < 0.001 for both variables). However, its relation to the lipid profile was weak (for cholesterol r = 0.16, P < 0.05; for triglycerides r = 0.17, P < 0.05) and disappeared after adjustment for BMI. Adiponectin was positively correlated with sex hormone-binding globulin (SHBG) (r = 0.39, P < 0.001) and inversely correlated with free-androgen index (r = -0.24, P < 0.01), estradiol and dehydroepiandrosterone sulfate (r = -0.165, P < 0.05; r = -0.21, P < 0.01 respectively). This difference remained significant for SHBG after adjustment for age and BMI (r = 0.20, P < 0.005). Finally, leptin was inversely correlated with total testosterone and SHBG (r = -0.44, P < 0.001; r = -0.30, P < 0.001 respectively); the relation with testosterone remained significant after adjustment for BMI. No significant relationship of either adiponectin or leptin with GH or IGF-I values was observed. In a stepwise multiple regression analysis, the independent predictors of adiponectin were HDL cholesterol, QUICKI, age and BMI (P < 0.0001, P = 0.005, P = 0.002 and P = 0.047 respectively) while for leptin, it was QUICKI, waist size and testosterone (P < 0.0001, P < 0.0001 and P = 0.004 respectively). The adjusted R2 values were 0.34 and 0.55. CONCLUSION: Our results show that in a healthy elderly male population, both adiponectin and leptin are related to insulin sensitivity, independent of age and BMI. While adiponectin is independently related to triglycerides and HDL cholesterol, the weak relationship of leptin to the lipid profile is completely mediated by BMI. In addition, and more interestingly, both adipocytokines are strongly associated with sex steroids. We speculate that SHBG is regulated by adiponectin and that there is an inhibitory effect of testosterone on the adiponectin gene. Further studies are needed to fully elucidate these relationships.

Adipocytes↗
PubMed2006

Low plasma adiponectin concentration is an indicator of the metabolic syndrome.

OBJECTIVE: Adiponectin is an adipocytokine known to be decreased in obesity. It functions in glucose and fatty acid metabolism and also has an anti-inflammatory role in microvasculature. We wanted to investigate the role of adiponectin as a biomarker of metabolic syndrome (MS) and see how the plasma adiponectin levels relate to new criteria of MS proposed by the International Diabetes Federation. METHODS: Plasma adiponectin concentrations were measured from total of 1041 Finnish subjects with an ELISA - a novel method planned in our laboratory. RESULTS: In both the sexes, the plasma adiponectin levels were lower in subjects with MS when compared with subjects with no diagnosis of MS (P< 0.001). Plasma adiponectin levels did not differ between subjects with National Cholesterol Education Program (ATPIII) and International Diabetes Federation-defined MS. Lower adiponectin levels were associated with different components of the MS and there was a trend towards decreasing adiponectin levels with an increasing number of components of MS in both the sexes. Subjects in the lowest adiponectin quartile had a significantly higher probability of having MS (P< 0.001), 4.4-fold in males and 7.5-fold in females, when compared with the corresponding individuals in the highest quartile. The probability increased in every lowering quartile of adiponectin level and was independent of body mass index. CONCLUSION: We conclude that adiponectin levels correlate with most of the components of the MS and the metabolic cluster per se.

Adiponectin↗
PubMed2003

Association between adiponectin and mediators of inflammation in obese women.

Low plasma levels of the anti-inflammatory factor adiponectin characterize obesity and insulin resistance. To elucidate the relationship between plasma levels of adiponectin, adiponectin gene expression in adipose tissue, and markers of inflammation, we obtained blood samples, anthropometric measures, and subcutaneous adipose tissue samples from 65 postmenopausal healthy women. Adiponectin plasma levels and adipose-tissue gene expression were significantly lower in obese subjects and inversely correlated with obesity-associated variables, including high-sensitive C-reactive protein (hs-CRP) and interleukin-6 (IL-6). Despite adjustment for obesity-associated variables, plasma levels of adiponectin were significantly correlated to adiponectin gene expression (partial r = 0.38, P < 0.05). Furthermore, the inverse correlation between plasma levels of hs-CRP and plasma adiponectin remained significant despite correction for obesity-associated variables (partial r = -0.32, P < 0.05), whereas the inverse correlation between adiponectin plasma levels or adiponectin gene expression in adipose tissue with plasma IL-6 were largely dependent on the clustering of obesity-associated variables. In conclusion, our data suggest a transcriptional mechanism leading to decreased adiponectin plasma levels in obese women and demonstrate that low levels of adiponectin are associated with higher levels of hs-CRP and IL-6, two inflammatory mediators and markers of increased cardiovascular risk.

Adiponectin↗
PubMed2004

Adiponectin is associated with vascular function independent of insulin sensitivity.

OBJECTIVE: Adiponectin has been proposed to play important roles in the regulation of energy homeostasis and insulin sensitivity. In experimental studies, adiponectin has also been found to inhibit vascular smooth muscle cell proliferation. Decreased adiponectin levels have been described in patients with coronary artery disease, and circulating adiponectin predicts cardiovascular death in patients with renal failure. Because adiponectin appears to influence both insulin sensitivity and vessel wall physiology, we examined insulin sensitivity and vascular function in relation with circulating adiponectin. RESEARCH DESIGN AND METHODS: We studied brachial artery vascular reactivity (high-resolution external ultrasound) and insulin sensitivity (minimal model) in 68 healthy subjects. Brachial artery vascular reactivity was also determined in 52 patients with altered glucose tolerance: 30 subjects with impaired fasting glucose (IFG) or glucose intolerance (GIT) and 22 patients with type 2 diabetes. RESULTS: Circulating adiponectin concentration was significantly associated with insulin sensitivity (r=0.29, P=0.02) and with fasting serum triglycerides (r=-0.29, P=0.02) in healthy subjects. In the latter, adiponectin levels were positively associated with arterial vasodilation in response to nitroglycerin (endothelium-independent vasodilation [EIVD], r=0.41, P=0.002) but not with flux-induced, endothelium-dependent vasodilation (EDVD) (r=0.007, P=NS). In contrast, EIVD was not significantly associated with adiponectin in subjects with IFG, GIT, or type 2 diabetes (r < or =0.10, P=NS). In a multiple linear regression analysis to predict EIVD in healthy subjects, age (P=0.012), sex (P=0.042), and adiponectin concentration (P=0.045), but not BMI, insulin sensitivity, or fasting triglycerides, contributed to 39% of EIVD variance. CONCLUSIONS: Serum adiponectin concentration appears to be significantly associated with vascular function in apparently healthy humans. This association seems to be independent of its link with insulin sensitivity.

Adiponectin↗
PubMed2005

Adiponectin level is reduced and inversely correlated with the degree of proteinuria in type 2 diabetic patients.

AIMS: Adiponectin seems to be an important modulator for metabolic and vascular diseases. We aimed to measure plasma adiponectin levels in type 2 diabetic patients and investigate any association with the severity of proteinuria. METHODS: 80 patients (mean age, 46.9 +/- 5.1 years; body mass index (BMI), 25.8 +/- 1.98 kg/m2) and 47 healthy volunteers (mean age, 46.1 +/- 5.5 years; BMI 26.74 +/- 2.23 kg/m2) were included. Plasma adiponectin concentration, insulin levels, homeostasis model assessment (HOMA) indices, calculated glomerular filtration rate (GFR), high sensitive C reactive protein (hsCRP) and biochemistry panel were determined in all subjects. The association between adiponectin concentration and proteinuria was evaluated. Additionally, the relationship between adiponectin and hsCRP and calculated GFR were also investigated. RESULTS: Adiponectin levels in patients were significantly lower than those of controls (n = 80; 8.76 +/- 4.50 microg/ml for patients, n = 47; 24.27 +/- 5.59 microg/ml for controls, p < 0.001). Plasma adiponectin levels in patients with proteinuria were significantly lower than those without proteinuria (n = 43; 6.81 +/- 2.82 microg/ml for proteinuria, n = 37; 11.98 +/- 3.32 microg/ml for no proteinuria, p < 0.001). There was a significant negative correlation between plasma adiponectin concentrations and the degree of proteinuria (r = -0.433, p < 0.001). There were also significant negative correlations between adiponectin concentrations and insulin levels as well as HOMA index in the patient group (r = -0.322, p = 0.004; r = -0.301, p = 0.032). Additionally there was a significant negative correlation between adiponectin and hsCRP levels in the patient group (r = -0.872, p < 0.001). CONCLUSION: The results show that adiponectin is lower in patients with type 2 diabetes and the levels are negatively correlated with the severity of proteinuria.

Adiponectin↗
PubMedDate not supplied

Testosterone administration suppresses adiponectin levels in men.

Testosterone (T) administration to men increases lean body mass and decreases fat mass. Adiponectin is produced by adipocytes and is thought to influence insulin sensitivity. In this study, we sought to determine whether experimental alterations in serum T change adiponectin levels in normal men. We measured adiponectin levels in 28 healthy men ages 18-35 years before and during treatment with a potent gonadotropin-releasing-hormone (GnRH) antagonist, acyline. Decreased T levels led to increased serum adiponectin within 7 days; maximal adiponectin levels were reached on day 21 (baseline 8.6 +/- 0.9 compared with 12.2 +/- 1.0 microg/mL on day 21, P <.05) and persisted through day 30, despite no significant changes in body mass index (BMI) and an increase in leptin. The addition of T to acyline, maintaining serum T levels within the normal range, prevented the increase in adiponectin following acyline alone. In a second study, 25 men aged 55-85 years were treated with 3 weeks of high-dose T (testosterone enanthate [TE], 600 mg/wk intramuscularly). With high serum T levels, adiponectin levels decreased significantly by day 21 of treatment (baseline 14.3 +/- 1.9 compared with 10.8 +/- 1.5 microg/mL, P <.05 vs baseline and placebo), BMI slightly increased, and leptin levels were decreased. We conclude that adiponectin levels increase within days of experimental T deficiency in normal men, and the increase in adiponectin is prevented by T replacement. Furthermore, supraphysiologic T administration results in decreased adiponectin levels. Our data support the hypothesis that T, its metabolites, or both directly suppress adipocyte production of adiponectin.

Adiponectin↗
PubMed2005

Enhanced urinary adiponectin excretion in IgA-nephropathy patients with proteinuria.

Adiponectin is secreted specifically by adipose tissue. It was reported that the serum adiponectin level was markedly increased in patients with end-stage renal disease and was positively associated with abnormal renal function in type 2 diabetes. Recently, we found that urinary adiponectin level was significantly increased in type 2 diabetic patients with overt diabetic nephropathy, but not in those without nephropathy. The aim of the present study was to evaluate whether the urinary adiponectin level is increased not only in diabetic patients with macroalbuminuria but also in IgA-nephropathy patients with macroalbuminuria. We measured urinary adiponectin levels in 24 healthy control subjects, 12 IgA-nephropathy patients, and 19 type 2 diabetic nephropathy patients, and they were, in medians, 2.24 microg/g creatinine (ranges of 0.85 to approximately 3.70), 59.2 microg/g creatinine (4.95 to approximately 186), and 33.1 microg/g creatinine (4.69 to approximately 114), respectively. In the two patient groups, urinary adiponectin levels were significantly higher than in control subjects (P<0.01). Moreover, positive correlations between urinary adiponectin levels and albumin-to-creatinine ratios were observed in IgA-nephropathy (R2=0.53, P<0.01) and diabetic nephropathy patients (R2=0.61, P<0.01), but not in control subjects. Serum adiponectin levels were unchanged in these three groups. These findings suggested that the increase of urinary adiponectin levels partly results from enhanced filtration of circulating adiponectin through the changes of glomerular permselectivity and intraglomerular hydruric pressure. However, clinical implication of urinary adiponectin excretion in healthy control remains to be elucidated.

Adiponectin↗
PubMed2005

Discrepancies in the regulation of plasma adiponectin and TNF-alpha levels and adipose tissue gene expression in obese African Americans with glucose intolerance: a pilot study using rosiglitazone.

OBJECTIVES: We examined the effects of rosiglitazone: 1) on glucose homeostasis, insulin action, beta-cell function, and plasma adiponectin and TNF-alpha (TNF-alpha) levels; and 2) the expression of adipose tissue TNF-alpha and adiponectin mRNA in African Americans with parental history of type 2 diabetes and with varying degrees of glucose intolerance. SUBJECTS AND METHODS: The study groups comprised 11 African Americans with normal glucose tolerance and six with diabetes and impaired glucose tolerance. The glucose-intolerant subjects received rosiglitazone (4-8 mg/day) every morning for 12 weeks. They underwent oral glucose tolerance test (OGTT) and subcutaneous adipose tissue biopsy (under local anesthesia) before and after 12 weeks of rosiglitazone therapy. Beta cell function and insulin resistance were calculated by using homeostasis model assessment (HOMA). Adipose tissue gene expression (mRNA) was measured by real-time polymerase chain reaction in both groups. RESULTS: Rosiglitazone monotherapy improved both fasting and two-hour serum glucose levels during OGTT in the glucose-intolerant group. However, mean serum insulin and C-peptide levels did not change when compared with baseline. Rosiglitazone monotherapy improved insulin resistance but not overall beta-cell secretion. Mean adiponectin levels at fasting and two hours after oral glucose ingestion were significantly (50%) lower in the glucose-intolerant group than in the control group. Rosiglitazone monotherapy significantly increased plasma adiponectin levels at fasting and two hours after oral challenge by two-fold in the glucose-intolerant group. Mean plasma TNF-alpha levels were not significantly different at fasting and after two hours during OGTT. Rosiglitazone had no significant effect on plasma TNF-alpha levels during OGTT. No significant differences were seen in the expression of adipose tissue TNF-alpha and adiponectin mRNA in the groups at baseline. Rosiglitazone did not significantly change the adipose tissue adiponectin and TNF-alpha mRNA. Rosiglitazone was well tolerated, without experiencing weight gain, edema, and liver function test abnormality in the glucose intolerant subjects. SUMMARY: Rosiglitazone improved glucose homeostasis and insulin resistance in high-risk African Americans. We found that adiponectin was lower in the glucose-intolerant group, while TNF-alpha was similar. While rosiglitazone increased plasma adiponectin, it had no effect on adipose tissue adiponectin mRNA. In addition, rosiglitazone had no effect on plasma TNF-alpha and adipose tissue TNF-alpha mRNA. We conclude that the metabolic effects of rosiglitazone could be mediated by adiponectin but not TNF-alpha in African Americans with glucose intolerance. Our study demonstrates that: 1) the role of adipocytokines in the etiology of type 2 diabetes in African Americans is complex; and 2) that adiponectin, but not TNF-alpha, could mediate the metabolic benefits of thiazolidinediones in African Americans with glucose intolerance.

Adiponectin↗