Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Adiponectin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources

Adherence to the Mediterranean dietary pattern is positively associated with plasma adiponectin concentrations in diabetic women.

BACKGROUND: Although the typical diet of the Mediterranean region has received much recognition over the past several years for its association with substantial health benefits, it remains unknown whether its favorable effects are mediated through changes in adiponectin concentrations. OBJECTIVE: The objective was to determine whether adherence to a Mediterranean-type diet is associated with higher plasma adiponectin concentrations. DESIGN: This study was a prospective and cross-sectional evaluation of plasma adiponectin concentrations and dietary data from 987 diabetic women from the Nurses' Health Study who had no history of cardiovascular disease at the time blood was drawn in 1990. RESULTS: Women who scored highest on a 9-point scale that measures adherence to a Mediterranean-type dietary pattern tended to be older, were less likely to be current smokers, had lower body mass indexes and waist circumferences, and had higher total energy intakes, physical activities, and plasma adiponectin concentrations than did women with the lowest scores. Median plasma adiponectin concentrations were 23% higher in women who most closely followed a Mediterranean-type diet than in low adherers after adjustment for age and energy intake (P < 0.01). Body composition, lifestyle, and medical history explained some, but not all, of the observed association between diet and adiponectin concentrations because high adherers tended to have greater adiponectin concentrations than did moderate or low adherers, even after adjustment for these variables. CONCLUSIONS: Our data suggest that, of the several components of the Mediterranean dietary pattern score, alcohol, nuts, and whole grains show the strongest association with adiponectin concentrations. Close adherence to a Mediterranean-type diet is associated with higher adiponectin concentrations.

Adiponectin↗

Adiponectin, risk of coronary heart disease and correlations with cardiovascular risk markers.

AIMS: We investigated the association of serum adiponectin concentrations with the risk of coronary heart disease (CHD) after careful adjustment for other established risk factors. In addition, we investigated the association between adiponectin levels and established sociodemographic and laboratory risk markers for CHD. METHODS AND RESULTS: Three hundred and twelve patients aged 40-68 with angiographically confirmed stable CHD and 476 age- and gender-matched controls were included in this case-control study. Adiponectin serum concentrations (adiponectin, R&D Systems, Wiesbaden, Germany), markers of inflammation and haemostasis, and an extensive lipid profile were determined. Adiponectin serum concentrations were lower in CHD patients when compared with age- and gender-matched controls, both in men (median 4.95 vs. 5.58 micromol/L, P=0.004) and in women (median 9.64 vs. 11.60 micromol/L, P=0.018). Adiponectin was strongly correlated with lipoproteins and apolipoproteins, in particular HDL-cholesterol (HDL-C), and to a lesser degree with markers of inflammation such as C-reactive protein, IL-6, or markers of coagulation or fibrinolysis. When compared with subjects with adiponectin serum concentrations in the lower quintile, the OR for CHD was 0.52 (95% CI 0.28-0.95) in the upper one after adjustment for covariates (P<0.007 for trend). After additional adjustment for HDL-C the association was strongly reduced, reflecting the close association between adiponectin and HDL-C. CONCLUSION: Adiponectin serum concentrations may have an important role in the development of CHD. The protective effect of high serum concentration may partly be mediated by effects on the metabolism of lipoproteins, especially on the metabolism of HDL.

Adiponectin↗

Serum adiponectin concentrations are decreased in women with endometriosis.

BACKGROUND: Adiponectin is a pleiotropic cytokine originally discovered as an adipocyte-specific gene product. Serum adiponectin concentrations have been reported to be low in women with endometrial cancer, breast cancer and uterine leiomyoma, suggesting possible involvement of adiponectin in these estrogen-related diseases. We thus addressed the relevance of adiponectin to endometriosis, an estrogen-dependent disease, in the present study. METHODS: Women with (n = 48) and without (n = 30) endometriosis undergoing laparoscopy were recruited in this study. Blood samples were collected, and serum adiponectin concentrations were measured using a specific enzyme-linked immunosorbent assay. The relationship between laparoscopic findings and serum adiponectin concentrations was analysed. RESULTS: The adiponectin concentrations in the serum of the women with endometriosis (median, 13.1 microg/ml; interquartile range, 10.2 - 16.7) were significantly lower than those of the women without endometriosis (15.9 microg/ml, 13.5 - 19.5; P = 0.008). A significant negative correlation was found between serum adiponectin concentrations and both endometriosis scores (R = - 0.307, P = 0.006) and adhesion scores (R = - 0.254, P = 0.026) of the revised American Society for Reproductive Medicine classification of endometriosis. CONCLUSIONS: The present findings suggest that adiponectin is implicated in the pathophysiology of endometriosis.

Adiponectin↗

Adiponectin, leptin and thyroid hormones in patients with chronic renal failure and on renal replacement therapy: are they related?

BACKGROUND: Renal function affects thyroid function and adipocytokines in many ways. We aimed to assess the adipocytokines adiponectin and leptin in relation to thyroid function in patients with chronic renal failure treated conservatively, in haemodialysed patients and in kidney allograft recipients. METHODS: The study was performed on 33 patients with chronic renal failure, 64 haemodialysed patients, 54 kidney allograft recipients and 38 healthy volunteers. Thyroid volume was estimated sonographically, thyroid hormones were determined by Micropartide Enzyme Immunoassay (MEIA), and serum adiponectin and leptin were assessed by radioimmunoassay. RESULTS: Serum thyroid-stimulating hormone (TSH), free T4 and free T3 were within the normal range. Adiponectin correlated significantly with free T3, haematocrit, haemoglobin, platelet count, body mass index (BMI) and urea in kidney allograft recipients. In haemodialysed patients, adiponectin correlated with free T4 and TSH, whereas leptin correlated with free T3. Multiple regression analysis showed that adiponectin was independently related only to the serum concentration of free T3 and urea in kidney transplant recipients and to free T4 and adequacy of dialysis in haemodialysed patients. In univariate analysis in patients with chronic renal failure, adiponectin correlated with free T3 and platelet count, and in healthy volunteers adiponectin correlated only with free T3 and triglycerides, and leptin correlated with BMI. CONCLUSIONS: We described novel relationships between adiponectin and thyroid hormones in patients with kidney diseases. However, possible pre-existing thyroid dysfunction prior to transplantation (during dialysis therapy) and immunosuppression after transplantation make all these findings relatively complex. Therefore, the relationships between adiponectin and the thyroid axis in patients with chronic renal failure, in haemodialysed subjects or in kidney transplant recipients merit additional studies.

Adiponectin↗

Serum levels of hepatoprotective peptide adiponectin in non-alcoholic fatty liver disease.

OBJECTIVE: Adiponectin is an adipose tissue-specific protein that has anti-inflammatory, antidiabetic and antiobesity effects. It has been suggested that adiponectin has a hepatoprotective role. Non-alcoholic fatty liver disease (NAFLD) is becoming more prevalent with increasingly adverse clinical outcomes. In this study, serum adiponectin levels were investigated in patients with NAFLD to determine its possible role on hepatic inflammation and injury. METHODS: Twenty-nine biopsy-proven NAFLD patients (14 women, 15 men) with elevated liver enzymes, 20 clinically diagnosed NAFLD patients (13 women, seven men) with normal liver enzymes, and 20 healthy adults (10 women, 10 men) were enrolled. From fasting blood samples, serum adiponectin levels were measured by enzyme-linked immunosorbent assay. The body mass index, serum glucose, insulin, cholesterol and triglyceride levels were determined. RESULTS: Serum adiponectin levels were 4.99+/-2.1, 9.49+/-3.91 and 7.74+/-4.41 micro/ml in the NAFLD with elevated liver enzymes, NAFLD with normal liver enzymes and healthy adult control groups, respectively. The mean serum adiponectin level in the NAFLD with elevated liver enzymes group was significantly lower than those of other groups tested (P<0.001). Insulin, cholesterol and triglyceride levels of NAFLD patients with elevated liver enzymes were significantly higher than control groups (P<0.05) but were not significantly different from the NAFLD group with normal liver enzymes (P>0.05). On histopathologic examination, the mean serum adiponectin levels of non-alcoholic steatohepatitis patients with grade 2 or more inflammatory activity was significantly lower than patients with grade 1 inflammatory activity (P=0.013). CONCLUSION: Serum adiponectin levels are significantly lower in NAFLD patients with elevated liver enzymes. Non-alcoholic steatohepatitis patients show lower levels of adiponectin with higher grades of inflammation.

Adiponectin↗

Lack of independent relationship between plasma adiponectin, leptin levels and bone density in nondiabetic female adolescents.

OBJECTIVES: Adiponectin has been implicated in the pathophysiology of metabolic syndrome and coronary artery disease in humans. Whether adiponectin is related to bone mineralization remains unclear in adults as well as in adolescents. In this study, we aimed to determine the relationship between plasma adiponectin, leptin concentrations and bone density, including total-body bone mineral density (BMD) and bone mineral content (BMC) in adolescence. PATIENTS AND MEASUREMENTS: We studied 105 nondiabetic female adolescents [mean age 15.4 +/- 1.9 years, and mean body mass index (BMI), 23.1 +/- 4.0 kg/m(2)]. A venous blood sample was taken after 12 h of fasting to measure fasting plasma adiponectin and leptin levels. BMD and BMC of the whole body were measured by dual-energy X-ray absorptiometry. RESULTS: In simple correlation analysis, plasma adiponectin and leptin levels correlated significantly with total-body BMD (r =-0.523 and r = 0.443, P < 0.001, respectively) and BMC (r =-0.471 and r = 0.396, P < 0.001, respectively). However, plasma adiponectin and leptin were related to both BMD and BMC in opposite directions. In multivariate linear regression analyses, only BMI or fat mass (FM) and Tanner stage, but not plasma adiponectin and leptin, were significantly related to BMD and BMC following adjustment for other variables. CONCLUSIONS: The results suggest that plasma adiponectin and leptin concentrations are not related to the total-body BMD and BMC independent of the chronological age, BMI or FM, and Tanner stage in nondiabetic female adolescents, although they were highly correlated in simple correlation analyses. The biologic roles of adiponectin in bone still need further clarification.

Adiponectin↗

Both intrauterine growth restriction and postnatal growth influence childhood serum concentrations of adiponectin.

OBJECTIVE: Insulin resistance has been linked to intrauterine growth restriction; adiponectin is a strong determinant of insulin sensitivity. We aimed at studying the contributions of birthweight and insulin sensitivity to circulating adiponectin in children born small for gestational age (SGA). DESIGN: Cross-sectional, hospital-based study dealing with insulin sensitivity in SGA children. PATIENTS: Thirty-two prepubertal children born SGA (age 5.4 +/- 2.9 years) and 37 prepubertal children born appropriate for gestational age (AGA, age 5.9 +/- 3.0 years). MEASUREMENTS: Serum levels of fasting glucose, serum lipids, insulin (immunometric assay) and adiponectin concentrations (ELISA) were assessed, and insulin resistance (IR) and insulin secretion (beta-cell) were calculated by the homeostasis model of assessment (HOMA). RESULTS: SGA children had similar HOMA-IR, HOMA-beta-cell and adiponectin concentrations than AGA children. However, in a separate analysis of subjects older than 3 years of age, SGA children showed higher HOMA-IR after adjusting for sex, age and body mass index (BMI) standard deviation score (SDS). Circulating adiponectin was higher in SGA children [adjusted means: 14.5 mg/l (95% CI 12.9-16.1) and 18.7 mg/l (95% CI 17.0-20.3) for AGA and SGA children, respectively; P < 0.0001]. Further analysis revealed that the group of overweight SGA (arbitrarily defined as being in the higher quartile for the BMI SDS distribution in the sample) had decreased serum concentrations of adiponectin, compared to lean SGA children [adjusted means: 12.9 mg/l (95% CI 9.3-16.5) vs. 19.0 (95% CI 16.8-21.3), respectively; P = 0.001]. In a multiple regression model, HOMA-IR and SGA status explained 35% and 15% of adiponectin variance, respectively. CONCLUSIONS: Prenatal growth restriction is associated with insulin resistance but relatively increased adiponectin concentrations, provided overweight does not ensue. The contributions of circulating adiponectin to the increased risks for developing insulin resistance and type-2 diabetes in formerly SGA subjects merit further studies.

Adiponectin↗

Obstructive sleep apnoea syndrome, plasma adiponectin levels, and insulin resistance.

OBJECTIVE: To investigate whether sleep-disordered breathing and/or plasma adiponectin levels are associated with insulin resistance independent of obesity or fat distribution in obstructive sleep apnoea syndrome (OSAS). DESIGN: Cross-sectional clinical study. PATIENTS: Two-hundred and thirteen Japanese patients with OSAS aged 27-80 years were divided into three groups: 30 with mild OSAS [apnoea-hypopnoea index (AHI) = 10.3 +/- 0.9 episodes/h, minimum oxygen saturation (min SpO2) = 87.3 +/- 0.9%], 98 with moderate OSAS (AHI = 28.9 +/- 0.6 episodes/h, min SpO2 = 82.1 +/- 0.7%), and 85 with severe OSAS (AHI = 68.1 +/- 2.8 episodes/h, min SpO2 = 72.3 +/- 1.6%). Twenty-one patients undergoing diabetic treatments (two mild, nine moderate and 10 severe) were excluded from the assessment of insulin resistance and plasma adiponectin measurements. MEASUREMENTS: Fat distribution [evaluated according to visceral (V) and subcutaneous (S) fat areas using computed tomography scanning at the umbilical level], blood pressure, metabolic parameters and hormones including insulin and adiponectin were measured. After full polysomnography, venous blood was collected between 0600 and 0700 h. RESULTS: Severe OSAS patients were more hypertensive than mild and moderate OSAS. Fasting plasma glucose (FPG) and fasting plasma insulin and homeostasis model assessment of insulin resistance (HOMA-IR) levels were all higher in severe OSAS than mild and moderate OSAS patients. HOMA-IR was correlated not only with obesity [body mass index (BMI), V and S areas] but also with apnoea (AHI, min SpO2 and desaturation time). Additionally, HOMA-IR was correlated positively with haemoglobin (Hb)A1c, systolic (SBP) and diastolic blood pressure (DBP), triglycerides and free fatty acids (FFA), and negatively with high density lipoprotein (HDL)-cholesterol, suggesting that insulin resistance is a key component of the metabolic syndrome in OSAS. Plasma adiponectin levels were not different between mild, moderate and severe OSAS groups. Plasma adiponectin levels were correlated with HOMA-IR and V area, but not AHI or min SpO2. Stepwise multiple regression analysis, however, revealed that BMI, AHI and plasma adiponectin were independently associated with HOMA-IR. CONCLUSION: Sleep-disordered breathing was associated with insulin resistance independent of obesity. Although plasma adiponectin was also an independent determinant of HOMA-IR in OSAS patients, plasma adiponectin was more closely related to obesity than to sleep apnoea. Although treatment of sleep-disordered breathing with nasal continuous positive airway pressure reportedly improves insulin sensitivity, our findings suggest that treatment of obesity is also essential in ameliorating insulin resistance at least through increased plasma adiponectin levels in OSAS.

Adiponectin↗

Associations between plasma adiponectin concentrations and liver histology in patients with nonalcoholic fatty liver disease.

OBJECTIVES: To explore associations between plasma adiponectin concentrations and liver histology in patients with nonalcoholic fatty liver disease (NAFLD). DESIGN AND PATIENTS: In a cross-sectional study, we enrolled 60 consecutive NAFLD patients and 60 age-, sex- and body mass index (BMI)-matched healthy controls. MEASUREMENTS: NAFLD (by liver biopsy), plasma adiponectin concentrations, insulin resistance (by homeostasis model assessment, HOMA-IR) and metabolic syndrome (MetS) features. RESULTS: NAFLD patients had a marked decrease in plasma adiponectin concentration (6.1 +/- 2.8 vs. 13.6 +/- 3.8 microg/ml, P < 0.001) compared with matched controls. MetS, as defined by the Adult Treatment Panel III (ATP III) criteria, and its individual components were more frequent among NAFLD patients. The marked differences in adiponectin concentrations that were observed between the groups were little affected by adjustment for age, sex, BMI, HOMA-IR score and MetS components. Notably, decreased adiponectin levels were closely associated with the degree of hepatic steatosis, necroinflammation and fibrosis (P < 0.001 for all) among NAFLD patients. By logistic regression analysis, low adiponectin levels independently predicted hepatic steatosis [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.5-5.8, P < 0.001] and necroinflammation (OR 3.1, 95% CI 1.9-7, P < 0.001), but not fibrosis (P = 0.07), after adjustment for age, sex, BMI, HOMA-IR and MetS components. CONCLUSIONS: NAFLD patients have markedly lower plasma adiponectin concentrations than control subjects. Low adiponectin levels are strongly associated with the severity of liver histology, thus further supporting the hypothesis that adiponectin might be involved in the development of NAFLD.

Adiponectin↗

Raised plasma adiponectin levels in type 1 diabetic pregnancies.

OBJECTIVES: Adiponectin has antidiabetic properties. Our aim was to determine plasma adiponectin levels during pregnancy and postpartum (PP), in women with type 1 diabetic mellitus (T1DM) and nondiabetic (ND) women. PATIENTS AND METHODS: Fasting plasma adiponectin and leptin levels were measured in 20 ND and 19 T1DM women, at 20 and 30 weeks' gestation, and 9 months' PP. Insulin measurements were made in ND women. RESULTS: In both groups, after accounting for body mass index (BMI), leptin levels increased during pregnancy (P < 0.01) and were significantly higher than PP (P < 0.001). However, no significant differences in leptin levels were noted between both groups at any stage (P = 0.46). Conversely, adiponectin levels were higher in T1DM at all stages of the study (P < 0.001). A significant fall in adiponectin levels was seen between 20 and 30 weeks' gestation in both groups (ND: P < 0.001; T1DM: P < 0.05); however, this decrease was attenuated in the T1DM group. Adiponectin levels PP were significantly higher than at 30 weeks (ND: P < 0.001; T1DM: P < 0.001). Furthermore, in T1DM, adiponectin appeared to correlate negatively with leptin, but only reached significance PP (r = -0.46, P < 0.001). In the ND group, adiponectin correlated negatively with both leptin (PP: r = -0.56, P < 0.0001) and insulin (P < 0.005). CONCLUSIONS: Higher adiponectin levels were noted in T1DM throughout gestation compared to ND pregnancies, with no difference in leptin levels. The significance of these findings needs to be determined.

Adiponectin↗

The transition to menopause reinforces adiponectin production and its contribution to improvement of insulin-resistant state.

OBJECTIVE: To evaluate the influence of menopausal status on the serum adiponectin concentration and investigate whether the contribution of adiponectin to insulin resistance is modified by menopausal status. SUBJECTS: We conducted a population-based, cross-sectional study of 207 premenopausal and 206 postmenopausal Japanese women. MEASUREMENTS: Data on anthropometric characteristics, fasting serum adiponectin, glucose and insulin concentrations were used. Insulin resistance (homeostasis model assessment of insulin resistance: HOMA-IR) was calculated. RESULTS: Postmenopausal women had significantly higher HOMA-IRs than premenopausal women [1.50 (1.42, 1.59) vs 1.18 (1.12, 1.24), geometric mean (1 standard error range), P = 0.005]. Paradoxically, adiponectin levels in postmenopausal women were also significantly higher than those in premenopausal women [10.3 (9.95, 10.7) vs 9.04 (8.71, 9.39), P = 0.028]. Multiple regression analysis showed that body mass index (BMI) was the only significantly independent predictor [standardized partial regression coefficients (sbeta) = 0.319, P < 0.001] for HOMA-IR among premenopausal women, whereas both BMI and adiponectin were the significant predictors among postmenopausal (sbeta = 0.334 and -0.141, P < 0.001 and < 0.05, respectively). When the subjects were restricted to those without metabolic disorders including high blood pressure, hypertriglyceridaemia, hypo-HDL cholesterolaemia and high fasting glucose, adiponectin (sbeta = -0.249, P < 0.05) was the only significant predictor for HOMA-IR among postmenopausal women but BMI was not significant (sbeta = 0.223, P = 0.075). CONCLUSIONS: The transition to menopause increases serum adiponectin concentrations. And the significant and negative association between adiponectin and HOMA-IR was observed only after menopause. Therefore, adiponectin may play a role in the improvement of an incipient insulin-resistant state after, rather than before, menopause.

Adiponectin↗

Circulating adiponectin reflects severity of liver disease but not insulin sensitivity in liver cirrhosis.

BACKGROUND: The adipocytokine adiponectin has been proposed to play important roles in the regulation of energy homeostasis, insulin sensitivity and shows anti-inflammatory properties. AIM: In this study we investigated the role of circulating adiponectin in different chronic liver diseases, its regulation by systemic anti-tumour necrosis factor (TNF)-alpha treatment and its hepatic metabolism. PATIENTS AND METHODS: Plasma adiponectin levels were determined in 87 patients with liver cirrhosis of different aetiologies, seven patients with alcoholic steatohepatitis undergoing systemic anti-TNF-alpha treatment, in 11 patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt implantation and in 21 healthy controls. RESULTS: Adiponectin levels were significantly higher in all subjects with liver cirrhosis of different aetiologies when compared with healthy controls and increased dependent on Child-Pugh classification. In subjects with alcoholic steatohepatitis, systemic anti-TNF-alpha treatment caused a significant decrease in circulating adiponectin. Adiponectin concentrations were similar in portal, hepatic and peripheral veins. No correlation between adiponectin levels and insulin resistance was found in any patient group. CONCLUSIONS: Our data suggest that circulating adiponectin is increased in liver cirrhosis independent of the aetiology of liver disease. We suggest that high adiponectin levels in chronic liver disease might reflect one of the body's anti-inflammatory mechanisms in chronic liver diseases.

Adiponectin↗

Adiponectin promotes endothelial cell differentiation from human peripheral CD14+ monocytes in vitro.

Adiponectin was revealed to have anti-atherogenic and anti-inflammatory properties and has been recently found to stimulate angiogenesis in vivo and in vitro. However, the role of adiponectin in endothelial differentiation remains unclear. The objective of this study was to investigate whether adiponectin can promote peripheral CD14(+) monocytes differentiation into endothelial cells (ECs). Human peripheral blood CD14(+) monocytes were cultured with or without adiponectin (10 microg/ml) for 10 days. Adiponectin significantly promoted EC morphology formation from CD14(+) monocytes. By flow cytometery analysis, cells treated with adiponection substantially increased mean fluorescence intensity of vascular endothelial growth factor receptor-2 (VEGFR-2) and endothelial nitric oxide synthase (eNOS), two specific endothelial markers, by 49.2 % and 53.9 %, respectively, as compared to control cells. By real time PCR analysis, the mRNA level of eNOS in adiponectin-treated cells was also increased by 31.9 % of that of the control cells. However, the mRNA levels of calponin and SMMHC, two specific SMC markers, in adiponectin-treated cells were decreased by 81.1 % and 79.7 % of that of the control cells, respectively. These data demonstrated that adiponectin could promote endothelial differentiation from peripheral blood CD14(+) monocytes by morphology change, upregulation of EC markers and downregulation of SMC markers. Adiponectin-promoted EC differentiation may contribute to vascular healing and angiogenesis.

Adiponectin↗

Phosphorylation of C/EBPbeta at a consensus extracellular signal-regulated kinase/glycogen synthase kinase 3 site is required for the induction of adiponectin gene expression during the differentiation of mouse fibroblasts into adipocytes.

Stimulation of adipogenesis in mouse preadipocytes requires C/EBPbeta as well as activation of the MEK/extracellular signal-regulated kinase (ERK) signaling pathway. In this study, we demonstrate that phosphorylation of C/EBPbeta at a consensus ERK/glycogen synthase kinase 3 (GSK3) site regulates adiponectin gene expression during the C/EBPbeta-facilitated differentiation of mouse fibroblasts into adipocytes. First, we show that exposure of 3T3-L1 preadipocytes to insulin, dexamethasone (DEX), and isobutylmethylxanthine (MIX) leads to the phosphorylation of C/EBPbeta at threonine 188. Pretreating the cells with a MEK1-specific inhibitor (U0126) significantly attenuates this activity. Similarly, these effectors activate the phosphorylation of T188 within an ectopic C/EBPbeta overexpressed in Swiss mouse fibroblasts, and this event involves both MEK1 and GSK3 activity. We further show that expression of C/EBPbeta (p34kD LAP isoform) in Swiss mouse fibroblasts exposed to DEX, MIX, and insulin induces expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and some adiponectin but that it does not activate expression of FABP4/aP2. In fact, complete conversion of these fibroblasts into lipid-laden adipocytes, which includes activation of FABP4 and adiponectin expression, requires their exposure to a potent PPARgamma ligand such as troglitazone. Expression of a mutant C/EBPbeta in which threonine 188 has been modified to alanine (C/EBPbeta T188A) can induce PPARgamma production in the mouse fibroblasts, but it is incapable of stimulating adiponectin expression in the absence or presence of troglitazone. Interestingly, replacement of T188 with aspartic acid creates a C/EBPbeta molecule (C/EBPbeta T188D) that possesses adipogenic activity similar to that of the wild-type molecule. The absence of adiponectin expression correlates with a reduced amount of C/EBPalpha in the adipocytes expressing the T188A mutant suggesting that C/EBPalpha is required for expression of adiponectin. In fact, ectopic expression of PPARgamma in C/EBPalpha-deficient fibroblasts (NIH 3T3 cells) produces a modest amount of adiponectin, whereas expression of both PPARgamma and C/EBPalpha in NIH 3T3 cells facilitates production of abundant quantities of adiponectin. These data demonstrate that phosphorylation of C/EBPbeta at a consensus ERK/GSK3 site is required for both C/EBPalpha and adiponectin gene expression during the differentiation of mouse fibroblasts into adipocytes.

Adipocytes↗

Circulating adiponectin concentrations in patients with congestive heart failure.

OBJECTIVES: To determine concentrations of adiponectin and its predictive value on outcome in a cohort of patients with congestive heart failure (CHF). METHODS: Serum and clinical data were obtained for outpatients with clinically controlled CHF (n = 175). Serum concentrations of adiponectin, C reactive protein, N-terminal pro-brain natriuretic peptide (NT-proBNP), interleukin (IL) -1beta, IL-6, IL-8, IL-10, IL-12, tumour necrosis factor alpha and CD-40 ligand were determined. The association of adiponectin with the clinical severity of CHF was sought as well as the predictive value of this adipokine on mortality, CHF hospitalisations or the occurrence of each of these end points. RESULTS: Concentrations of adiponectin were significantly increased in patients with CHF. Patients with higher New York Heart Association class had significantly higher serum concentrations of adiponectin. Adiponectin serum concentrations were lower in patients with diabetes and CHF as well as in patients with ischaemic cardiomyopathy. Serum adiponectin concentration was positively associated with age and NT-proBNP but was negatively correlated with C reactive protein concentrations. Serum adiponectin above the 75th centile was found to be an independent predictor of total mortality, CHF hospitalisations or a composite of these end points over a two-year prospective follow up. CONCLUSION: Adiponectin is increased in CHF patients and predicts mortality and morbidity.

Adiponectin↗

Adiponectin is stimulated by adrenalectomy in ob/ob mice and is highly correlated with resistin mRNA.

Plasma levels of the adipocyte product adiponectin, a putative insulin-sensitizing agent, are reduced in obesity, whereas plasma levels of resistin, an agent that some believe to confer insulin resistance, are thought to increase with obesity. Because adrenalectomy can increase insulin sensitivity, we hypothesized that adrenalectomy would increase expression of adiponectin and decrease expression of resistin. Therefore, we measured adiponectin mRNA, adiponectin peptide, and resistin mRNA in adrenalectomized ob/ob mice. Adrenalectomy restored adiponectin expression in ob/ob mice to wild-type levels and stimulated adiponectin peptide to above wild-type levels. Surprisingly, expression of adiponectin and resistin was highly positively correlated even after statistical removal of effects of insulin, glucose, and adiposity. In addition, adiponectin and resistin expression were also highly correlated in diet-induced obese mice. The data support a role for adiponectin in mediating some effects of adrenalectomy on insulin sensitivity.

Adiponectin↗

Effects of DGAT1 deficiency on energy and glucose metabolism are independent of adiponectin.

Mice lacking acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), an enzyme that catalyzes the terminal step in triacylglycerol synthesis, have enhanced insulin sensitivity and are protected from obesity, a result of increased energy expenditure. In these mice, factors derived from white adipose tissue (WAT) contribute to the systemic changes in metabolism. One such factor, adiponectin, increases fatty acid oxidation and enhances insulin sensitivity. To test the hypothesis that adiponectin is required for the altered energy and glucose metabolism in DGAT1-deficient mice, we generated adiponectin-deficient mice and introduced adiponectin deficiency into DGAT1-deficient mice by genetic crosses. Although adiponectin-deficient mice fed a high-fat diet were heavier, exhibited worse glucose tolerance, and had more hepatic triacylglycerol accumulation than wild-type controls, mice lacking both DGAT1 and adiponectin, like DGAT1-deficient mice, were protected from diet-induced obesity, glucose intolerance, and hepatic steatosis. These findings indicate that adiponectin is required for normal energy, glucose, and lipid metabolism but that the metabolic changes induced by DGAT1-deficient WAT are independent of adiponectin and are likely due to other WAT-derived factors. Our findings also suggest that the pharmacological inhibition of DGAT1 may be useful for treating human obesity and insulin resistance associated with low circulating adiponectin levels.

Adiponectin↗

Transcardiac adiponectin gradient is independently related to endothelial vasomotor function in large and resistance coronary arteries in humans.

Adiponectin, an adipocyte-derived protein, has been shown to have vasculoprotective effects. This study examined the possible relationship between coronary vasomotor function and the transcardiac gradient of adiponectin, reflecting adiponectin utilization and/or accumulation in the coronary vascular bed. The epicardial diameter and blood flow response of the left anterior descending coronary artery to intracoronary infusions of ACh was analyzed in 108 consecutive subjects who had a normal coronary angiogram and left ventriculogram. Adiponectin levels were measured by ELISA in plasma obtained from the aortic root (Ao) and the anterior interventricular vein (AIV). Adiponectin levels in the AIV were lower than levels in the Ao. In multivariate linear regression analysis, the transcardiac gradient of adiponectin (Ao - AIV levels) showed a positive correlation with increases in epicardial coronary diameter and coronary blood flow in response to ACh that was independent of traditional coronary risk factors. The transcardiac gradient of adiponectin was not significantly associated with the coronary dilator response to isosorbide dinitrate and the coronary flow response to sodium nitroprusside. In other groups of patients with coronary spastic angina (n = 41) or microvascular angina (n = 32) who had impaired coronary vasomotor responses, there was no significant gradient of adiponectin between the Ao and AIV. The transcardiac gradient of adiponectin may modulate endothelial vasomotor function in large and resistance coronary arteries and may play a role in the pathogenesis of diseases presenting with coronary vasomotor dysfunction.

Adiponectin↗