Adiponectin is a circulating hormone that is produced exclusively by adipocytes and has anti-inflammatory and anti-atherogenic properties. The hypothesis that there are differences in adiponectin levels between stable and unstable coronary-artery disease patients remains controversial. Furthermore, the potential relationships between the plasma adiponectin level and the inflammatory and non-inflammatory markers (oxidized low density lipoprotein and nitric oxide) in patients with stable and unstable coronary-artery disease relative to normal subjects have not been assessed.
To assess whether plasma adiponectin levels differ among patients with stable and unstable coronary-artery disease and among control subjects, and to correlate plasma adiponectin level with inflammatory and clinical risk factors (such as oxidized-LDL and nitric oxide) in these patients.
This study included 50 control subjects, 50 stable angina patients and 50 unstable angina patients with angiographically documented coronary-artery disease. Plasma adiponectin and oxidized-LDL levels were determined using an enzyme immunoassay. Plasma nitric oxide, high sensitivity C-reactive protein and lipid profile levels were also measured.
Plasma adiponectin levels were lower in the unstable angina patients (4.9±1.30 µg/mL) than in the stable angina patients (6.34±1.0 µg/mL) or in the controls (9.25±1.8 µg/mL); these levels were also significantly lower in stable angina patients versus controls (p<0.001). Plasma adiponectin levels were negatively correlated with oxidized-LDL, high sensitivity C-reactive protein, lipid profile and other clinical risk factors but positively correlated with nitric oxide.
Plasma adiponectin levels were found to be lower in both stable and unstable angina patients relative to control subjects, and the correlation between plasma adiponectin and cardiovascular markers is weakened in these patients.
Adiponectin; Nitric oxide; Ox-LDL; Stable; Unstable
Cardiac autonomic neuropathy (CAN) is a common complication of diabetes associated with poor prognosis. In addition, the autonomic imbalance is associated with cardiovascular disease (CVD) in diabetes. It is thought that adipocytokines contribute to the increased risk of vascular complications in patients with type 2 diabetes mellitus (T2DM). However, literature data on the association between CAN with adipocytokines such as leptin, tumor necrosis factor-alpha (TNF-alpha), adiponectin in subjects with T2DM is limited.
Therefore, in the present study, we examined the relationship between fasting serum leptin, TNF- alpha and adiponectin and CAN in Korean T2DM patients.
A total of 142 T2DM patients (94 males, 48 females) were recruited. CAN was assessed by the five tests according to the Ewing's protocol and the time and frequency domain of the heart rate variability (HRV) was evaluated. Serum TNF-alpha and adiponectin levels were measured using enzyme-linked immunosorbent assay and serum leptin levels were measured using radioimmunoassay.
Although, the mean levels of leptin, TNF-alpha and adiponectin were not significantly different between the groups with and without CAN, the levels of leptin and adiponectin had a tendency to increase as the score of CAN increased (p = 0.05, p = 0.036). Serum leptin levels demonstrated a negative correlation with low frequency (LF) in the upright position (p = 0.037). Regarding TNF-alpha, a significant negative correlation was observed with SDNN and RMSSD in the upright position (p = 0.023, p = 0.019). Adiponectin levels were not related to any HRV parameters. Multivariate logistic regression analysis demonstrated that the odds of CAN increased with a longer duration of diabetes (1.25, [1.07-1.47]) and higher homeostatic model of assessment-insulin resistance (HOMA-IR) (5.47, [1.8-16.5]). The relative risks for the presence of CAN were 14.1 and 51.6 for the adiponectin 2nd, 3rd tertiles when compared with first tertile (p-value for trend = 0.022).
In the present study, the higher serum adiponectin levels and HOMA-IR were associated with an increased risk for the presence of CAN. Also, the CAN score correlated with the serum adiponectin. Serum adipocytokines such as leptin and TNF-alpha were significantly correlated with parameters of HRV, representative markers of CAN. Future prospective studies with larger number of patients are required to establish a direct relationship between plasma adipocytokine concentrations and the development or severity of CAN.
Cardiac autonomic neuropathy; heart rate variability; leptin; TNF- alpha; adiponectin; type 2 diabetes mellitus
Recent evidence demonstrated that the circulating adipokines were associated with the onset of acute coronary syndrome (ACS) including unstable angina pectoris (UAP) and acute myocardial infarction (AMI). As a novel adipokine, chemerin has been related to atherosclerosis and the presence of coronary artery disease. However, the plasma levels of chemerin in patients with ACS have yet to be investigated.
Plasma levels of chemerin and adiponectin were measured by an enzyme-linked immunosorbent assay (ELISA) in 60 patients with stable angina pectoris (SAP), 60 patients with UAP, 60 patients with AMI and 40 control patients. Left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) were measured using a GE ViVid E7 ultrasonography machine, and the severity of coronary stenosis in patients was estimated with a Gensini coronary score following coronary angiography.
Plasma chemerin levels were significantly higher in ACS patients than in the control and SAP groups, while plasma adiponectin levels were significantly lower in ACS patients than the control group. A correlation analysis revealed that plasma chemerin levels were positively correlated with the levels of C-reactive protein (CRP) (r = 0.29, P < 0.01) and LVEDD (r = 0.27, P < 0.01) but negatively correlated with LVEF (r = -0.45, P < 0.01) and that plasma adiponectin levels were positively correlated with LVEF (r = 0.53, P < 0.01) but negatively correlated with CRP (r = -0.33, P < 0.01) and LVEDD (r = -0.30, P < 0.01). Although significant correlations between chemerin, adiponectin and BMI or the Gensini coronary score were found in patients with SAP, neither chemerin nor adiponectin was correlated with BMI and the Gensini coronary score in patients with ACS. Furthermore, both chemerin (OR 1.103, 95% CI 1.065 to 1.142; P = 0.001) and adiponectin (OR 0.871, 95% CI 0.776 to 0.970; P = 0.018) were independently associated with the presence of ACS.
Chemerin is a novel biomarker of acute coronary syndrome but not of stable angina pectoris.
Chemerin; Adiponectin; Acute coronary syndrome; Inflammation; Left ventricular function
To assess the relationship between serial serum leptin levels in patients with acute myocardial infarction (AMI) who received thrombolysis and the degree of coronary atherosclerosis, coronary reperfusion, echocardiographic findings, and clinical outcome. 51 consecutive patients presenting with AMI were studied. Clinical characteristics including age, sex, body mass index (BMI) and cardiovascular risk factors were recorded. Serial serum leptin levels at the time of admission and subsequently at 0, 6, 12, 24, 36, 60 hours afterwards were obtained. Coronary angiography was performed in 34 patients; the relation between serum leptin levels and evidence of coronary reperfusion as well as the extent of coronary atherosclerosis according to the coronary artery surgery study classification (CASS) were evaluated. Echocardiographic evaluation was performed in all patients. 36 matched patients were enrolled as control group who had serum leptin level 9.4 ± 6.5 ng/ml.
The patients mean age was 50.5 ± 10.6 years. There were 47 males and 3 females. 37.1% were diabetics, 23.5% were hypertensive, 21.6% were dyslipidemic and 22.7% were obese (BMI ≥ 30). Leptin concentrations (ng/ml) increased and peaked at the 4th sample (36 hrs) after admission (mean ± SD) sample (1) =9.55 ± 7.4, sample (2) =12.9 ± 8.4, sample (3) =13.8 ± 10.4, sample (4) =18.9 ± 18.1, sample (5) =11.4 ± 6.5, sample (6) =10.8 ± 8.9 ng/ml. There was a significant correlation between serum leptin and BMI (r = 0.342; p = 0.03). Leptin levels correlated significantly to creatine kinase level on the second day (r = 0.43, p ≤ 0.01). Significant correlation of mean serum leptin with the ejection fraction (P < 0.05) was found. No difference in timing of peak serum leptin between patients who achieved coronary reperfusion vs. those who did not (p = 0.8). There was a trend for an increase in the mean serum leptin levels with increasing number of diseased vessels. There was no correlation between serum leptin levels and outcome neither during the hospitalization nor at 9 months follow up.
Serum leptin levels increase after myocardial infarction. Serum leptin level may be a predictor of the left ventricular ejection fraction and the degree of atherosclerosis but not of coronary reperfusion.
Serum leptin; Acute myocardial infarction; Angiographic findings; Echocardiography
Objective: To investigate whether concentrations of plasma adiponectin constitute a significant coronary risk factor, with particular focus on the relation between plasma concentrations of adiponectin and the development of acute coronary syndrome (ACS).
Subjects and methods: Plasma concentrations of adiponectin were measured in 123 patients with coronary artery disease (CAD) and in 17 control participants. Patients were divided into three groups according to condition type: acute myocardial infarction (AMI) group (n = 59), unstable angina pectoris (UAP) group (n = 28), and stable angina pectoris (SAP) group (n = 36).
Results: Plasma concentrations of adiponectin correlated negatively with body mass index (r = −0.18, p < 0.05), serum triglyceride (r = −0.25, p < 0.01), and fasting glucose concentrations (r = −0.21, p < 0.05), but correlated positively with age (r = 0.26, p < 0.01), high density lipoprotein cholesterol concentrations (r = 0.35, p < 0.01), and low density lipoprotein particle size (r = 0.37, p < 0.01). Plasma concentrations of adiponectin in patients with ACS, in both the AMI and UAP groups, were significantly lower than those in patients with SAP and in the control group (ACS, 6.5 (3.0) μg/ml; SAP, 11.3 (5.9) μg/ml; control 12.8 (4.3) μg/ml; p < 0.01). Additionally, plasma concentrations of adiponectin in patients with CAD (7.9 (4.6) μg/ml, p < 0.01) were significantly lower than in the control group. There were, however, no significant differences between patients with SAP and the control group (p = 0.36). Multiple logistic regression analysis showed that smoking, fasting glucose concentration, and low log adiponectin concentration correlated independently with the development of an ACS.
Conclusions: The findings suggest that measurement of plasma concentrations of adiponectin may be of use for assessing the risk of CAD and may be related to the development of ACS.
adiponectin; LDL particle size; acute coronary syndrome; coronary artery disease; coronary risk factor
Atherosclerosis is the primary cause of coronary artery disease (CAD). There is increasing recognition that lesion composition rather than size determines the acute complications of atherosclerotic disease. Low serum adiponectin levels were reported to be associated with coronary artery disease and future incidence of acute coronary syndrome (ACS). The impact of adiponectin on lesion composition still remains to be determined.
We measured serum adiponectin levels in 303 patients with stable typical or atypical chest pain, who underwent dual-source multi-slice CT-angiography to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed or non-calcified. In bivariate analysis adiponectin levels were inversely correlated with total coronary plaque burden (r = −0.21, p = 0.0004), mixed (r = −0.20, p = 0.0007) and non-calcified plaques (r = −0.18, p = 0.003). No correlation was seen with calcified plaques (r = −0.05, p = 0.39). In a fully adjusted multivariate model adiponectin levels remained predictive of total plaque burden (estimate: −0.036, 95%CI: −0.052 to −0.020, p<0.0001), mixed (estimate: −0.087, 95%CI: −0.132 to −0.042, p = 0.0001) and non-calcified plaques (estimate: −0.076, 95%CI: −0.115 to −0.038, p = 0.0001). Adiponectin levels were not associated with calcified plaques (estimate: −0.021, 95% CI: −0.043 to −0.001, p = 0.06). Since the majority of coronary plaques was calcified, adiponectin levels account for only 3% of the variability in total plaque number. In contrast, adiponectin accounts for approximately 20% of the variability in mixed and non-calcified plaque burden.
Adiponectin levels predict mixed and non-calcified coronary atherosclerotic plaque burden. Low adiponectin levels may contribute to coronary plaque vulnerability and may thus play a role in the pathophysiology of ACS.
Adiponectin, an adipocyte-derived hormone, is implicated in diabetes mellitus type 2 and atherosclerosis. The study was designed to investigate whether serum adiponectin levels in patients with both coronary artery disease (CAD) and diabetes mellitus type 2 (T2DM) are lower than in patients with CAD alone and control subjects.
In this present study, we measured serum adiponectin levels in consecutive CAD patients with and without T2DM and investigated whether decreased adiponectin is associated with risk factors of CAD.
Materials and Methods:
The study included 198 subjects, 138 patients with CAD (72 of whom had both CAD and T2DM), and 60 control subjects. We measured serum adiponectin, interleukin-6 (IL-6) and insulin by ELISA. In addition, Lipid profile, glucose and anthropometrical measurements were performed in all subjects.
The results revealed significant difference in serum adiponectin levels between patients with CAD+T2DM and patients with CAD alone (3.80 ± 1.52 vs. 5.25 ± 2.35, P = 0.007), between patients with CAD and control (5.25 ± 2.35 vs. 7.04 ± 3.32, P = 0.001), and between patients with CAD + T2DM and control (3.80 ± 1.52 vs. 7.04 ± 3.32, P < 0.001). Serum adiponectin level was significantly higher in women in contrast to men (5.97 ± 3.15 vs. 4.62 ± 2.81 µg/ml, P = 0.002). Serum adiponectin levels were correlated significantly with insulin (r = -0.178, P = 0.013), total cholesterol (r = -0.313, P < 0.001), low density lipoprotein (r = -0.154, P = 0.016), body mass index (r = -0.171, P = 0.016), glucose (r = -0.202, P = 0.006), HOMA-IR (r= -0.251, P = 0.001), and IL-6 levels (r = -0.321, P = 0.001). Adiponectin was correlated positively only with high density lipoprotein (r = 0.389, P < 0.001).
It is speculated that increased insulin resistance and increase in other adipokines such as IL-6 may contribute to the decreased serum levels of adiponectin in patients with both CAD and T2DM.
Coronary Artery Disease; Diabetes Mellitus, Type 2; Interleukin-6
Calorie restriction prevents mammary tumor (MT) development in rodents. Usually, chronic calorie restriction (CCR) has been implemented. In contrast, intermittent calorie restriction (ICR) has been less frequently used. Recent studies indicate that when a direct comparison of the same degree of CCR vs. ICR was made using MMTV-TGF-α mice which develop MTs in the second year of life, ICR provided greater protection than CCR in delaying MT detection and reducing tumor incidence. Adiponectin and leptin are two adipocytokines secreted from adipose tissue which have opposite effects on many physiological functions, including proliferation of human breast cancer cells. A recent study indicated that a low adiponectin/leptin ratio was associated with breast cancer. We evaluated the relationship of adiponectin and leptin to MT development in MMTV-TGF-α calorie-restricted mice at several ages. Mice were enrolled at 10 weeks of age and subjected to 25% caloric reduction implemented either chronically or intermittently. Mice were euthanized at designated time points up to 74 weeks of age. Serum samples were collected to measure adiponectin and leptin concentrations. Both CCR and ICR mice had significantly reduced MT incidence. For the groups studied, serum leptin increased over time, while there was a trend for an increase in serum adiponectin levels in ad libitum and ICR mice, with no change in CCR mice between 10 and 74 weeks of age. The adiponectin/leptin ratio was significantly reduced as mice aged, but this ratio in ICR mice was significantly higher than that for ad libitum and CCR mice. No correlation was noted between serum adiponectin and leptin. These findings demonstrate that intermittent calorie restriction delays the early development of MTs. This delay was associated with reduced serum leptin levels following the restriction phases of the protocol. Additionally, serum leptin levels correlated with body weight and body fat in the groups studied.
adiponectin; leptin; adiponectin/leptin ratio; mammary tumor; breast cancer; mouse; calorie restriction; energy restriction
Aim. This study was designed to clarify the role of leptin and adiponectin in preeclampsia (PE) pathogenesis and different subtypes of preeclampsia. Method. This case control study was performed in 45 PE patients and 45 healthy controls matched for age, BMI, and ethnicity. Serum leptin and adiponectin levels were determined by enzyme linked immunosorbent assay (ELISA). Results. Maternal serum leptin and adiponectin were significantly higher in PE women than controls. Serum leptin was elevated in early onset preeclampsia (EOPE) and late onset preeclampsia (LOPE) compared to controls. Among PE patients, serum leptin was higher in EOPE than LOPE women. However, serum adiponectin was not different between EOPE and LOPE women. The serum leptin was significantly higher in severe PE than mild PE. The serum adiponectin was significantly elevated in severe PE compared to controls. Significant positive correlation was observed between leptin and adiponectin and also between leptin and BMI in controls. Moreover significant positive correlation was observed between adiponectin and BMI in PE patients and controls. Conclusion. The present study showed that serum leptin level may play a significant role as a biomarker to differentiate early and late onset PE and also its relation to BMI and severity of disease.
Recognition of adipose-related signaling in surgery is increasing, though direct interrogation of human adipose has been sparse. Few scenarios rival uremia for health impact. We hypothesized that adipose from uremic patients holds a relatively higher adipose derived hormone and pro-inflammatory adipokine signature; we simultaneously evaluated the impact of clinical parameters on adipose phenotype.
Materials and Methods
Adipose was harvested from surgical patients. Histology and protein analyses were completed for select mediators.
In the 71 patient cohort, mean age=63.4y; 63.3% had diabetes, 49.2% had hyperlipidemia and 53.5% had coronary disease. Compared to non-uremic patients, uremic patients had 1/10th the levels of leptin (p<0.001), 1/3rd the levels of adiponectin (p<0.001), and 3-fold higher resistin (p<0.001). Females had 6-fold higher leptin, 1.5-fold higher adiponectin and 2-fold higher TNF-α but equivalent resistin. There were differences in mediators when stratified by age. In both the obese/non-obese strata, we observed a concordant pattern of association (magnitude/significance) of uremia and leptin/adiponectin/resistin. No differentials in other mediators emerged upon BMI stratification. Multiple regression analysis for leptin/adiponectin/resistin (with age/gender/uremia as independent variables) showed uremia as the highest independent predictor of all three mediators.
Advanced chronic kidney disease is associated with perturbations in adipose derived hormones (leptin/adiponectin/resistin). Adipose adiponectin and leptin (in contrast to reported plasma levels) was lower in uremic patients; there is an inverse correlation between adipose resistin and renal function. Compared with other clinical parameters including BMI, uremia dominates overall in determining adipose phenotype, highlighting the complex biologic interplay between uremia and adipose biology.
Uremia; chronic kidney disease; adipose tissue; leptin; adiponectin; resistin
Background & objectives:
Hyperthyroidism is associated with increased food intake, energy expenditure and altered body composition. This study was aimed to evaluate the role of adipocytokines in weight homeostasis in patients with hyperthyroidism.
Patients (n=27, 11men) with hyperthyroidism (20 Graves’ disease, 7 toxic multinodular goiter) with mean age of 31.3±4.2 yr and 28 healthy age and body mass index (BMI) matched controls were studied. They underwent assessment of lean body mass (LBM) and total body fat (TBF) by dual energy X-ray absorptiometer (DXA) and blood sample was taken in the fasting state for measurement of leptin, adiponectin, ghrelin, insulin, glucose and lipids. Patients were re-evaluated after 3 months of treatment as by that time all of them achieved euthyroid state with carbimazole therapy.
The LBM was higher (P<0.001) in healthy controls as compared to hyperthyroid patients even after adjustment for body weight (BW), whereas total body fat was comparable between the two groups. Serum leptin levels were higher in patients with hyperthyroidism than controls (22.3±3.7 and 4.1±0.34 ng/ml, P<0.001), whereas adiponectin levels were comparable. Plasma acylated ghrelin was higher in patients than in controls (209.8±13.3 vs 106.2±8.2 pg/ml, P<0.05). Achievement of euthyroidism was associated with significant weight gain (P<0.001) and significant increase in lean body mass (P<0.001). The total body fat also increased but insignificantly from 18.4±1.8 to 19.9±1.8 kg. There was significant decrease (P<0.05) in serum leptin and acylated ghrelin but adiponectin levels remained unaltered after treatment. Serum leptin positively correlated with TBF and this correlation persisted even after adjustment for BW, BMI, gender and age (r=0.62, P=0.001). However, serum leptin and acylated ghrelin did not correlate with the presence or absence of hyperphagia.
Interpretation & conclusion:
Patients with hyperthyroidism predominantly had decreased lean body mass which increased after achievement of euthyroidism with carbimazole. The hyperphagia and the alterations in weight homeostasis associated with hyperthyroidism were independent of circulating leptin and ghrelin levels.
Adipocytokines; body composition; ghrelin; hyperphagia; hyperthyroidism
Alzheimer's disease (AD) and atherosclerosis share common vascular risk
factors such as arterial hypertension and hypercholesterolemia.
Adipocytokines and CD34+ progenitor cells are associated
with the progression and prognosis of atherosclerotic diseases. Their role
in AD is not adequately elucidated.
Methods and Findings
In the present study, we measured in 41 patients with early AD and 37 age-
and weight-matched healthy controls blood concentrations of adiponectin and
leptin by enzyme linked immunoabsorbent assay and of CD34+
progenitor cells using flow cytometry. We found significantly lower plasma
levels of leptin in AD patients compared with the controls, whereas plasma
levels of adiponectin did not show any significant differences (AD vs.
control (mean±SD): leptin:8.9±5.6 ng/mL vs.16.3±15.5
ng/mL;P = 0.038; adiponectin:18.5±18.1
µg/mL vs.16.7±8.9 µg/mL;P = 0.641).
In contrast, circulating CD34+ cells were significantly
upregulated in AD patients (mean absolute cell count±SD:253±51
vs. 203±37; P = 0.02) and showed an inverse
correlation with plasma levels of leptin
(r = −0.248; P = 0.037).
In logistic regression analysis, decreased leptin concentration
(P = 0.021) and increased number of
CD34+ cells (P = 0.036) were both
significantly associated with the presence of AD. According to
multifactorial analysis of covariance, leptin serum levels were a
significant independent predictor for the number of CD34+
cells (P = 0.002).
Our findings suggest that low plasma levels of leptin and increased numbers
of CD34+ progenitor cells are both associated with AD. In
addition, the results of our study provide first evidence that increased
leptin plasma levels are associated with a reduced number of
CD34+ progenitor cells in AD patients. These findings
point towards a combined involvement of leptin and CD34+
progenitor cells in the pathogenesis of AD. Thus, plasma levels of leptin
and circulating CD34+ progenitor cells could represent an
important molecular link between atherosclerotic diseases and AD. Further
studies should clarify the pathophysiological role of both adipocytokines
and progenitor cells in AD and possible diagnostic and therapeutic
Adiponectin is an adipocyte specific cytokine which, in contrast to other adipokines, has been described to have antiinflammatory, antithrombotic, and anti-atherogenic properties. This study evaluates the association between plasma adiponectin levels with acute coronary syndrome (ACS) and angiographic coronary lesion severity in Indian population. Ninety patients included in the study were divided in two groups in 1 : 1 ratio—patients admitted with a diagnosis of ACS and those without ACS. Adiponectin and other risk markers are measured in forty-five consecutive patients in each group undergoing coronary angiography. Patients without ACS were found to have higher adiponectin (16.47 ± 7.88 μg/mL) levels than patients with ACS (9.03 ± 3.13 μg/mL) (P < 0.001). In multiple regression analysis adjusted for all other risk markers, higher adiponectin levels remain positively associated with a lower risk of ACS (P value > 0.002). The greatest increase in risk for ACS was seen at adiponectin levels ≤12.20 μg/mL in study subjects. The adiponectin levels were inversely related to the angiographic severity of coronary artery stenosis increases (P value > 0.02). The study concluded that higher adiponectin levels are independently associated with lower risk of ACS, and patients with severe angiographic coronary artery disease have lower levels of adiponectin.
Adiponectin plays a role as a positive contributor to the stabilization of atherosclerotic plaques. Circulating total adiponectin (Total-APN) levels associates with the number of coronary vessels in men with coronary artery disease (CAD). We recently reported that adiponectin binds to C1q in human blood, and serum C1q-binding adiponectin (C1q-APN) /Total-APN levels are associated with CAD in type 2 diabetic subjects. The present study investigated the relationship between circulating C1q-APN levels and the number of angiographic coronary artery vessel in male subjects.
The study subjects were 53 male Japanese patients who underwent diagnostic coronary angiography. Blood total adiponectin (Total-APN), high-molecular weight adiponectin (HMW-APN), C1q-APN and C1q were measured by enzyme-linked immunosorbent assays.
Serum C1q-APN/Total-APN ratio significantly increased in subjects with single and multi-vessel coronary diseases (p = 0.029 for trend, the Kruskal-Wallis test). However, serum Total-APN, HMW-APN, C1q-APN and C1q levels did not correlate with number of diseased coronary vessels.
Serum C1q-APN/Total-APN ratio progressively increases in men with single and multi-vessel coronary disease.
Adiponectin; C1q; C1q-binding adiponectin; Coronary artery disease; Angiographic coronary vessel
To our knowledge, this is the first study exploring the association of childhood non-Hodgkin's lymphoma (NHL) with serum adiponectin and leptin levels in a nationwide case-control series. In addition, expression of adiponectin receptors in NHL specimens was assessed, and the association between adipokines and childhood NHL survival and prognosis was examined.
Patients and Methods
We studied 121 incident childhood (0 to 14 years) NHL cases registered in the Nationwide Registry for Childhood Hematological Malignancies (1996 to 2006) and an equal number of matched controls, for whom sociodemographic, lifestyle, prenatal characteristics, and fasting blood serums were collected. Serum adiponectin and leptin levels were determined. Immunohistochemisty for adiponectin receptors expression was performed on commercially available adult NHL specimens (n = 30) and in a subset of childhood NHL cases (n = 6) that were available. Summary statistics, multiple conditional logistic regression analyses, and survival analysis were performed.
Higher serum adiponectin, but not leptin, levels were independently associated with childhood NHL (odds ratio, 1.82; 95% CI, 1.30 to 2.56), after adjusting for obesity and established risk factors. Higher adiponectin levels at diagnosis were positively associated with relapse and poor survival, but hormone levels did not differ among NHL subtypes. Adiponectin receptors 1 and 2 were present in 90% and 57% of adult samples and in 83% and 100% of childhood NHL samples, respectively.
Elevated serum adiponectin, but not leptin, levels are independently associated with childhood NHL and poor prognosis. Adiponectin receptors are expressed in NHL, suggesting that adiponectin may represent not only a potential clinically significant diagnostic and prognostic marker but also a molecule that may be implicated in NHL pathogenesis.
There is growing evidence of a positive correlation between asthma and obesity in children and adults. Leptin and adiponectin regulate several metabolic and inflammatory functions. This study aims to evaluate serum leptin and adiponectin concentrations in asthmatic school children to investigate their association with obesity and the degree of asthma control. Obese asthmatic (OA) and nonobese asthmatic (NOA) children, aged 7 to 14, were randomly enrolled in this prospective study. Data on demographic, anthropometric, serum lipids, and spirometric measures and allergy status were collected and analyzed. Serum leptin was significantly higher (25.8 ± 11.1 versus 8.7 ± 11.1; P < 0.0001) and adiponectin levels were lower (2.5 ± 1.2 versus 5.4 ± 2.9; P < 0.0001) in OA compared to NOA children. The uncontrolled group had higher leptin and lower adiponectin levels compared to well and partially controlled asthma. BMI was positively correlated with leptin (r = 0.79; P < 0.001) and negatively with adiponectin (r = −0.73; P < 0.001). Mean BMI and leptin levels were observed to be higher in girls compared to boys. Stepwise multiple linear regression analysis showed that higher BMI and female gender had significant effect on serum leptin levels. Among asthmatic children higher serum leptin and lower adiponectin levels were significantly associated with obesity and showed no significant association with degree of asthma controls.
Obesity is rapidly becoming a pandemic and is associated with increased carcinogenesis. Obese populations have higher circulating levels of leptin in contrast to low concentrations of adiponectin. Hence, it is important to evaluate the dynamic role between adiponectin and leptin in obesity-related carcinogenesis. Recently, we reported the oncogenic role of leptin including its potential to increase tumor invasiveness and migration of hepatocellular carcinoma (HCC) cells. In the present study, we investigated whether adiponectin could antagonize the oncogenic actions of leptin in HCC. We employed HCC cell-lines HepG2 and Huh7, nude mice-xenograft model of HCC and immunohistochemistry-data from tissue-microarray to demonstrate the antagonistic role of adiponectin on the oncogenic actions of leptin. Adiponectin treatment inhibited leptin-induced cell proliferation of HCC cells. Using scratch-migration and electric cell-substrate impedance-sensing based migration assays, we found that adiponectin inhibited leptin-induced migration of HCC cells. Adiponectin treatment effectively blocked leptin-induced invasion of HCC cells in matrigel invasion assays. While leptin inhibited apoptosis in HCC cells, we found that adiponectin treatment induced apoptosis even in the presence of leptin. Analysis of the underlying molecular mechanisms revealed that adiponectin treatment reduced leptin-induced Stat3 and Akt phosphorylation. Adiponectin also increased suppressor of cytokine signaling (SOCS3), a physiologic negative regulator of leptin signal transduction. Importantly, adiponectin significantly reduced leptin-induced tumor burden in nude mice. In HCC samples, leptin expression significantly correlated with HCC proliferation as evaluated by Ki-67 while adiponectin expression correlated significantly with increased disease-free-survival and inversely with tumor size and local recurrence.
Collectively, these data demonstrate that adiponectin has the molecular potential to inhibit the oncogenic actions of leptin by blocking downstream effector molecules.
Adipocytokines; Obesity; HCC; Invasion; Migration
Adiponectin, an adipocyte-derived protein, modulates a number of metabolic processes. Methadone maintenance treatment (MMT) changes the level of hormones produced by adipose tissue in addicts. However, current data remains contradictory.
The aim of this study was to evaluate the effect of MMT on serum adiponectin levels in drug addicts.
Materials and Methods:
Twenty-five drug abusers with a mean age of 37.4 ± 8.7 years were referred to the Baharan Hospital, Zahedan, and 22 healthy age-matched control subjects with a mean age of 35 ± 9.5 years were enrolled in the study. Addicts were treated with methadone at (40 to 120 mg/d) for six months. Measurement of anthropometric parameters, serum adiponectin, and biochemical parameter levels, were assessed in the addicts, before and after six months of MMT, but only once in the healthy controls.
The mean basal serum adiponectin level was not significantly lower in the drug abuser group compared to the healthy subjects (P > 0.05). After six months of MMT, the mean serum adiponectin level of the drug addicts was not significantly different from their mean baseline level or that of the healthy subjects (P > 0.05). However, the mean baseline serum adiponectin level was significantly lower in overweight/obese addicts when compared to underweight patients and healthy individuals (P < 0.001). After six months of MMT, the mean level of serum adiponectin increased significantly in the underweight subjects compared to the normal weight and overweight/obese subjects (P < 0.0001) and the control group (P < 0.001). Adiponectin concentration was correlated inversely with body mass index and positively correlated with waist circumference and serum high-density lipoprotein levels.
This study showed that MMT did not markedly alter the concentration of serum adiponectin in drug abusers. However, in regard to the variations in the serum lipid profiles and anthropometric parameters, the findings indicated that low concentrations of serum adiponectin might play a role in the pathogenesis of obesity and other metabolic abnormalities. Thus, more long-term studies with larger sample sizes are recommended.
Adiponectin; Drug Users; Methadone
The aim of the study was to estimate the association between anthropometric obesity parameters, serum concentrations of ghrelin, resistin, leptin, adiponectin and homeostasis model assessment (HOMA-IR) in obese non-diabetic insulin-sensitive and insulin-resistant patients.
Study subjects included 37 obese (body mass index [BMI] ≥30 kg/m2) out-clinic patients aged 25 to 66 years. Insulin resistance was evaluated by HOMA-IR. Serum fasting concentrations of glucose, insulin, ghrelin, adiponectin, resistin and leptin were measured by using the ELISA method. Body weight, waist and hip circumferences were measured to calculate BMI and waist-to-hip ratio (WHR) values for all the patients. According to HOMA-IR, patients were divided into two groups: A, insulin sensitive (n=19); and B, insulin resistant (n=18).
Patients with insulin resistance have greater mean waist circumference (WC) higher mean serum insulin level and leptin concentration, but lower concentrations of adiponectin and ghrelin. In the insulin-sensitive patient group we observed positive correlations between BMI and HOMA-IR, WC and HOMA-IR, and adiponectin and leptin, and negative correlations between ghrelin and HOMA-IR, WC and adiponectin, and WHR and adiponectin. In the insulin-resistant group, there was a positive correlation between resistin and ghrelin and a negative correlation between WHR and leptin.
Waist circumference, adiponectin, leptin and ghrelin are associated with insulin resistance and may be predictors of this pathology.
adipokines; ghrelin; insulin resistance; obese patients; waist circumference
Hypertension often coexists with obesity. Adipokines, ghrelin and insulin play important roles in the pathogenesis of both diseases. The aim of this study was to compare adiponectin, leptin, resistin, insulin and ghrelin mean serum concentrations and insulin resistance (HOMA-IR) in normo- and hypertensive patients with obesity.
Material and methods
All included patients were divided on the following groups: non-diabetic hypertensive patients with class I obesity (group A, n = 21) and class II/III obesity (group B, n = 10), and normotensive obese (class I)patients (group C, n = 7). Correlations between obesity indices (body mass index [BMI], waist-to-hip ratio [WHR], waist circumference [WC]), HOMA-IR, and hormone and adipokine serum levels were also analyzed.
Leptin level and HOMA-IR were significantly higher in group B compared to group C (9.74 ±3.88 ng/ml vs. 4.53 ±3.00 ng/ml; p < 0.02 and 3.30 ±1.59 vs. 1.65 ±0.41; p < 0.02, respectively). A negative correlation between WC and adiponectin level (R = –0.6275; p < 0.01) and a positive correlation between WC and insulin concentration (R = 0.5122; p< 0.05) as well as with HOMA-IR (R = 0.5228; p < 0.02) were found in group A. Negative correlations between BMI and ghrelin level (R = –0.7052; p < 0.05), WHR and adiponectin level (R = –0.6912; p < 0.05) and WHR and leptin level (R = –0.6728; p < 0.05) were observed in group B.
Insulin resistance and leptin may be important pathogenic factors in hypertensive patients with severe obesity. Indices of abdominal obesity (WC, WHR) correlate better than BMI with HOMA-IR, insulin, adiponectin and leptin serum levels in hypertensive obese patients.
insulin resistance; obesity; adipokines; ghrelin; hypertension
The aim of this study was to investigate serum leptin, adiponectin and paraoxonase1 levels in adult females receiving pharmacotherapy for various psychiatric disorders.
The study group consisted of 32 obese females (mean age 40.53 ± 11.00 years, mean body mass index 35.44 ± 5.33 kg/m2) who were receiving treatment for psychiatric disorders, and the control group included 22 obese females (mean age 35.95 ± 9.16 years, mean body mass index 30.78 ± 3.33 kg/m2) who were free of psychiatric disorders. Analyses were performed using a bioelectrical impedance device. Fasting blood samples were obtained for complete blood count and various biochemical tests, including determination of leptin, adiponectin and paraoxonase1 activity.
Body mass index, waist and hip circumference, body fat percentage, fasting blood glucose, insulin, glycosylated hemoglobin, homeostasis model assesment of insulin resistance, alanine transaminase, aspartate tarnsaminase, and leptin levels were significantly higher in the study group than in controls. Although body weight was positively correlated with leptin levels in both groups, body weight was negatively correlated with adiponectin levels in the control group and positively correlated with adiponectin levels in the study group. In the study group, body mass index and hip circumference correlated positively with leptin levels, hip circumference correlated positively with adiponectin levels, and waist to hip ratio correlated positively with paraoxonase levels. In the control group, body mass index as well as waist and hip circumferences were positively correlated with leptin levels. Weight, body mass index, and hip circumference were also negatively correlated with the adiponectin/leptin ratio in the control group.
This study indicates a higher risk for obesity-related disorders, particularly metabolic syndrome, diabetes and cardiovascular disease, in patients treated with psychiatric drugs.
Adiponectin; Paraoxonase; Psychiatric drugs; Obesity
The relationship of saliva with plasma protein levels makes saliva an attractive diagnostic tool. Plasma levels of adiponectin and leptin in healthy individuals or diabetes mellitus patients have been previously reported. Nevertheless, salivary levels of these adipocytokines in patients with metabolic syndrome (MS) have never been investigated. This study was aimed to determine adiponectin and leptin levels in saliva and plasma from patients with metabolic syndrome, and evaluate any correlation of these levels with MS.
Forty-six healthy and 82 MS patients were enrolled. Demographic data and blood biochemistries were recorded. Saliva and plasma adiponectin and leptin levels were analyzed by enzyme-linked immunosorbent assay (ELISA).
Adiponectin and leptin were higher in plasma than in saliva (p < .001). Plasma adiponectin was decreased and plasma leptin increased in patients with MS (p < .001). Salivary adiponectin and salivary leptin were not different between healthy subjects and MS patients (p = .619 and p = .523). Correlation between salivary and plasma adiponectin showed significant association (r = .211, p = .018) while salivary and plasma leptin had no correlation (r = -.161, p = .069). Significant correlation was observed between the salivary adiponectin/salivary leptin ratio and plasma adiponectin (r = .371, p < .001), but not with any component of MS. Increased triglyceride and waist circumference were associated with risk of having a low level of plasma adiponectin (OR = 1.009; 95% CI 1.002–1.015 and OR = 1.125; 95% CI 1.029–1.230). For leptin, body mass index and high-density lipoprotein cholesterol (HDL-C) were associated with a high level of plasma leptin (OR = 1.621; 95% CI 1.212–2.168 and OR = .966; 95% CI .938–.996). The OR for MS as predicted by plasma adiponectin was .928 (95% CI .881-.977).
This study showed that salivary adiponectin and leptin do not correlate with MS. Although correlation between salivary and plasma adiponectin was observed, no association with MS was observed. Only plasma adiponectin may be useful for the prediction of MS.
Saliva; Plasma; Adiponectin; Leptin; Metabolic syndrome
Although high-molecular-weight (HMW) adiponectin is believed to protect against atherosclerosis, the association between HMW adiponectin and the composition of coronary plaques is unknown. We evaluated whether the HMW to total adiponectin ratio was associated with the presence of coronary plaque and its composition using multi-slice computed tomography coronary angiography (MSCTCA).
Serum total and HMW adiponectin levels were measured in 53 consecutive patients (age, 71) with >50% coronary artery stenosis detected by MSCTCA. A low-attenuation coronary plaque was defined as a plaque with a mean CT density <50 Hounsfield units. Multivariate logistic regression analyses were performed to evaluate the predictors of the presence of low-attenuation coronary plaques, which is thought to be high risk, on CT.
Decreased serum levels of total as well as HMW adiponectin were significantly associated with the presence of at least one calcified or non-calcified coronary artery plaque (total adiponectin level: odds ratio 0.76, 95% CI 0.58–0.99, P = 0.048; HMW adiponectin level: odds ratio 0.65, 95% CI 0.42–0.99, P = 0.047). A low ratio of HMW to total adiponectin was significantly associated with the presence of low-attenuation coronary plaques (4.55, 1.94–21.90, P = 0.049). However, neither the total adiponectin nor the HMW adiponectin level was associated with the presence of low-attenuation coronary plaques.
Lower total or HMW adiponectin levels are associated with the presence of calcified and non-calcified coronary plaques, whereas a lower ratio of HMW to total adiponectin associated with the presence of low-attenuation coronary plaques (thought to be high risk). Measurement of total and HMW adiponectin levels and the HMW to total adiponectin ratio may be useful for risk stratification of coronary artery plaques.
Adiponectin; High-molecular-weight adiponectin; Coronary artery plaque; Coronary low-attenuation plaque
The increasing incidence of obesity, leading to metabolic complications is now recognized as a major public-health problem. Insulin resistance is a central abnormality of the metabolic syndrome, or syndrome X, originally hypothesized by Reaven Insulin resistance is more strongly linked to intra abdominal fat than to fat in other depots. Adipose tissue secretes numerous factors (adipokines) known to markedly influence lipid and glucose/insulin metabolism, oxidative stress, and cardiovascular integrity. Some of these adipokines have been shown to directly or indirectly affect insulin sensitivity through modulation of insulin signaling and the molecules involved in glucose and lipid metabolism. A pilot study was conducted with 80 healthy subjects who were non diabetic, non hypertensive and having no family history of hypertension, the aim was to evaluate the correlation of adiponectin and leptin levels with obesity and insulin resistance markers in healthy north Indian adult population. Serum leptin, adiponectin and insulin was estimated by sandwich ELISA method. In our study, Leptin correlated significantly with BMI (P value of 0.0000), WC (P value = 0.007), and HC (P value = 0.000). leptin showed significant positive correlation with fasting insulin (P value 0.002), post prandial insulin (P value = 0.000) and HOMA-IR (P value = 0.002). Adiponectin showed significant positive correlation with triglycerides (P value = 0.038), strong negative correlation with HDL-cholesterol (P value = 0.017). Serum concentrations of leptin are associated with central body fat distribution. Insulin resistance and adiponectin is associated with dyslipidemia and these all disorders may ultimately lead to metabolic syndrome.
Adiponectin; Leptin; Insulin resistance; Cytokines
We examined the associations between adiponectin or leptin and serum ICAM-1 levels in seventy-six hypercholesterolemic patients (mean age 59 yrs, 25 males and 51 females, LDL-cholesterol>=130mg/dL at screening). Blood lipid profiles and HOMA-IR derived from fasting glucose and insulin concentrations were determined. Serum levels of adiponectin, leptin and ICAM-1 were analyzed using ELISA. The results showed that serum levels of leptin were positively associated with serum levels of ICAM-1 independent of age, sex and BMI (r =0.392, p<0.001). Serum levels of adiponectin were negatively associated with serum levels of ICAM-1 independent of age, sex and BMI (r =-0.343, p<0.005). Stepwise multiple linear regression analysis showed that serum leptin was an independent factor to be associated with serum ICAM-1 levels after adjusting for age, sex, BMI, alcohol intake, smoking status, blood lipids such as total cholesterol, triglyceride, HDL cholesterol and LDL cholesterol and HOMA-IR (p<0.001). With respect to adiponectin, its association with serum ICAM-1 was attenuated but still significant when further adjustments were made for age, sex, BMI, alcohol intake, smoking status, blood lipids such as total cholesterol, triglyceride, HDL cholesterol and LDL cholesterol and HOMA-IR (p<0.005). In conclusion, this study suggests that adiponectin and leptin are associated with endothelial derived inflammation.
Leptin; adiponectin; ICAM-1; adipokine; hypercholesterolemia