Background and Aim
Adipose tissue is the most abundant endocrine tissue in the body, producing leptin, a hormone important in regulating hunger, and adiponectin, a hormone involved in insulin sensitivity and inflammation. The aim of this study was to assess the impact of gastric bypass surgery (GBS) on leptin levels and its relation to adipose tissue expression of adiponectin.
Omental and subcutaneous adipose tissue and serum were obtained from 40 obese patients undergoing GBS, 13 patients one-year or more post-GBS, and 16 non-obese individuals (BMI 20-29). Adiponectin gene expression was measured by quantitative real time PCR and the gene expression was normalized for the GAPDH gene. Serum leptin and adiponectin were measured by a high-sensitivity enzymatic assay.
Leptin levels were significantly lower in the post-GBS patients as compared to pre-GBS patients (19.8±6.7 vs. 59.0±5.1, p=0.0001) and similar to non-obese controls (19.8±6.7 vs. 18.2±4, p=0.8). Univariate analysis showed an inverse correlation between serum leptin levels and omental adiponectin gene expression (r=-0.32, p=0.01).
Gastric bypass surgery results in resolution of the leptin resistance status that characterizes obese subjects. We also demonstrated a significant correlation between leptin and adiponectin. This correlation provides preliminary evidences for studying a potential adiponectin-leptin cross-talking that may represent one of the physiological pathways responsible for the regulation of food intake in humans.
adiponectin; leptin; gastric bypass surgery; bariatric surgery; visceral fat; adipose tissue
We evaluated the association of the sex hormone pattern and the serum level of the main adipokines to metabolic syndrome (MS) and its components in 199 pharmacologically untreated subjects. Men and women included in the age-class subgroups were matched for body mass index, waist circumference, blood pressure, heart rate, fasting plasma glucose, and plasma lipids. Men without MS had significantly lower leptin/adiponectin ratio than men with MS. Women without MS had lower leptin and leptin/adiponectin ratio than women with MS but had significantly higher adiponectin, estrone, and dehydroepiandrosterone levels. In men, the leptin/adiponectin ratio is the main factor associated to MS diagnosis (OR: 3.36, 95% CI 1.40–8.08), while in women adiponectin alone appears to be a protective factor (OR: 0.87, 95% CI 0.79–0.95). In conclusion, in a sample of pharmacologically untreated subjects, leptin/adiponectin ratio seems to be the factor more strongly associated to MS and its components.
Adiponectin and leptin are two adipokines secreted by white adipose tissue that regulate insulin sensitivity. Previously we reported that adiponectin but not leptin release depends on GGA-coated vesicle formation, suggesting that leptin and adiponectin may follow different secretory routes. Here we have examined the intracellular trafficking pathways that lead to the secretion of these two hormones. While adiponectin and leptin displayed distinct localization in the steady-state, treatment of adipocytes with brefeldin A inhibited both adiponectin and leptin secretion to a similar level, indicating a common requirement for class III ADP-ribosylating factors and an intact Golgi apparatus. Adiponectin secretion was significantly reduced by endosomal inactivation in both 3T3L1 and rat isolated adipocytes, whereas this treatment had no effect on leptin secretion. Importantly, endosomal inactivation completely abolished the insulin stimulatory effect on adiponectin release in rat adipocytes. Confocal microscopy studies revealed colocalization of adiponectin with endogenous rab11 a marker for the recycling endosome, and with expressed rab5-GFP mutant (rab5Q75L) a marker for the early endosome compartment. Colocalization of adiponectin and rab5Q75L was increased in endosome inactivated cells. Consistent with these findings adiponectin secretion was reduced in cells expressing mutants of Rab11 and Rab5 proteins. In contrast, expression of an inactive (kinase dead) mutant of Protein Kinase D1 moderately but significantly inhibited leptin secretion without altering adiponectin secretion. Taken together, these results suggest that leptin and adiponectin secretion involve distinct intracellular compartments and that endosomal compartments are required for adiponectin but not for leptin secretion.
adipokine; adiponectin; leptin; secretion; trafficking; adipocyte
The control of growth and nutritional status in the foetus and neonate is a complex mechanism, in which also hormones produced by adipose tissue, such as adiponectin and leptin are involved. The aim of this study was to evaluate levels of adiponectin, leptin and insulin in appropriate (AGA) and small for gestational age (SGA) children during the 1st year of life and to correlate these with auxological parameters.
In 33 AGA and 29 SGA infants, weight, length, head circumference, glucose, insulin, adiponectin and leptin levels were evaluated at the second day of life, and at one, six and twelve months, during which a portion of SGA could show catch-up growth (rapid growth in infants born small for their gestational age).
Both total and isoform adiponectin levels were comparable between AGA and SGA infants at birth and until age one year. These levels significantly increased from birth to the first month of life and then decreased to lower values at 1 year of age in all subjects. Circulating leptin concentrations were higher in AGA (2.1 ± 4.1 ng/ml) than in SGA neonates (0.88 ± 1.03 ng/ml, p < 0.05) at birth, then similar at the 1st and the 6th month of age, but they increased in SGA from six months to one year, when they showed catch-up growth. Circulating insulin levels were not statistically different in AGA and SGA neonates at any study time point. Insulin levels in both AGA and SGA infants increased over the study period, and were significantly lower at birth compared to one, six and 12 months of age.
During the first year of life, in both AGA and SGA infants a progressive decrease in adiponectin levels was observed, while a difference in leptin values was correlated with the nutritional status.
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
Introduction. Experiments on genetically modified animals have discovered a complex cross-regulation between adipokines (leptin, adiponectin) and osteocalcin. The relationships between these molecules in human osteoporosis are still unclear. We evaluated the hypothesis of a bidirectional link between adipokines and osteocalcin. Materials and Methods. In a cross-sectional study of 294 older patients with osteoporotic hip fracture, we estimated serum concentrations of leptin, adiponectin, resistin, osteocalcin, parameters of mineral metabolism, and renal function. Results. After adjustment for multiple potential confounders, serum osteocalcin concentration was inversely associated with resistin and positively with leptin, leptin/resistin ratio, and adiponectin/resistin ratio. In multivariate regression models, osteocalcin was an independent predictor of serum leptin, resistin, leptin/resistin, and adiponectin/resistin ratios. Conclusions. Our data support the bidirectional regulation between osteocalcin and adipokines, but contrary to the genetically modified animal models, in older subjects with osteoporotic hip fracture, serum osteocalcin is positively associated with leptin and inversely with resistin.
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
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
Leptin and adiponectin are adipocyte-secreted hormones that regulate energy homeostasis and metabolism. Because their roles in the neonatal period and in early childhood are poorly understood, we aimed in this prospective cohort study to determine the extent to which umbilical cord blood leptin and adiponectin concentrations predict measures of adiposity and growth at 3 years of age.
PATIENTS AND METHODS
We studied 588 children participating in the prospective prebirth cohort study Project Viva. We examined associations of cord blood leptin and adiponectin levels with weight changes during the first 6 months of life, 3-year circulating leptin and adiponectin concentrations, and the following adiposity-related outcomes at 3 years of age: BMI z score, height-for-age z score, and sums of triceps and subscapular skinfold thicknesses to represent overall adiposity, as well as subscapular/triceps skinfold ratio to represent central adiposity.
Cord blood leptin and adiponectin were each directly associated with the duration of gestation and birth weight for gestational age z scores. Cord blood leptin levels were negatively associated with change in weight-for-length, weight-for-age, and length-for-age z scores between birth and 6 months of age. Similarly, cord blood adiponectin was negatively associated with change in weight-for-length and weight-for-age z scores. After adjusting for several maternal and child factors related to obesity, each 10 ng/mL increment of cord blood leptin was associated with a reduction in BMI z score and higher leptin levels at 3 years but not with skinfold thicknesses. Each 10 µg/mL increment of cord blood adiponectin was positively associated with a higher subscapular skinfold thickness/triceps skinfold thickness ratio at 3 years.
Lower cord blood leptin levels are associated with smaller size at birth but more pronounced weight gain in the first 6 months of life and higher BMI at 3 years of age. Cord blood adiponectin levels are also directly associated with birth weight for gestational age, inversely associated with weight gain in the first 6 months of life, and predict an increase in central adiposity at age 3 years.
leptin; adiponectin; children; obesity
Adiponectin is a protein hormone produced by adipose tissue whose circulating levels are inversely related to adiposity and inflammation. Adiponectin circulates as oligomers, from the low molecular weight trimer to the high molecular weight octodecamer (18mer) Each oligomer has distinct biological activities, which include enhancement of insulin sensitivity and metabolic control, and suppression of inflammation. Adiponectin occurs in human milk at higher concentrations than leptin. The adiponectin in human milk is almost entirely of the high molecular weight form, the form with the highest activity in controlling many types of metabolic processes. Human adiponectin fed to infant mice is transported across the intestinal mucosa into the serum. An inverse relationship between adiponectin levels in milk and adiposity (weight-for-height) of the breastfed infant was observed, and could be due to modulation of infant metabolism by milk adiponectin, and may be related to the observed protection against obesity by breastfeeding. Human milk may be a medium whereby the hormonal milieu (in response to internal factors and the environment) of the mother can be used to communicate with the breastfed infant to modify infant metabolic processes. Transmission of information from mother to infant through milk may allow adaptation to fluctuating environmental conditions.
infant development; body weight; BMI; adiposity
We evaluated the hypothesis that plasma levels of adiponectin and leptin are independently but oppositely associated with coronary calcification (CAC), a measure of subclinical atherosclerosis. In addition, we assessed which biomarkers of adiposity and insulin resistance are the strongest predictors of CAC beyond traditional risk factors, the metabolic syndrome and plasma C-reactive protein (CRP).
Adipokines are fat-secreted biomolecules with pleiotropic actions that converge in diabetes and cardiovascular disease.
We examined the association of plasma adipocytokines with CAC in 860 asymptomatic, non-diabetic participants in the Study of Inherited Risk of Coronary Atherosclerosis (SIRCA).
Plasma adiponectin and leptin levels had opposite and distinct associations with adiposity, insulin resistance and inflammation. Plasma leptin was positively (top vs. bottom quartile) associated with higher CAC after adjusting for age, gender, traditional risk factors and Framingham Risk Scores (FRS) [tobit regression ratio 2.42 (95% CI 1.48–3.95, p=0.002)] and further adjusting for metabolic syndrome and CRP [ratio 2.31 (95% CI 1.36–3.94, p=0.002)]. In contrast, adiponectin levels were not associated with CAC. Comparative analyses suggested that levels of leptin, IL-6 and sol-TNFR2 as well as HOMA-IR predicted CAC scores but only leptin and HOMA-IR provided value beyond risk factors, the metabolic syndrome and CRP.
In SIRCA, while both leptin and adiponectin levels were associated with metabolic and inflammatory markers, only leptin was a significant independent predictor of CAC. Of several metabolic markers, leptin and the HOMA-IR index had the most robust, independent associations with CAC.
Adipokines are fat-secreted biomolecules with pleiotropic actions and represent novel markers for cardiovascular risk. We examined the association of plasma adipocytokines with CAC in 860 asymptomatic, non-diabetic Caucasians. Leptin was positively (top vs. bottom quartile) associated with higher CAC even after adjustment for age, gender, traditional risk factors, Framingham Risk Score, metabolic syndrome, and CRP [ratio 2.31 (95% CI 1.36–3.94, p=0.002)]. Adiponectin levels were not associated with CAC. Comparative analyses suggested that levels of leptin, IL-6 and sol-TNFR2 as well as HOMA-IR predicted CAC scores, but only leptin and HOMA-IR provided value beyond risk factors, the metabolic syndrome and CRP.
Adiponectin; Leptin; Coronary Artery Calcification; Atherosclerosis; Inflammation
Objective. To evaluate leptin and adiponectin as biomarkers of metabolic syndrome (MS) risk factors even in nonobese children/adolescents. Methods. Serum leptin, adiponectin, leptin:adiponectin ratio, lipids, glucose, and insulin concentrations as well as body size parameters and pubertal development were evaluated in a large population of Chinese children/adolescents (n = 3505, 6–18 years, 1722 girls and 1783 boys). Results. Leptin concentration increased while adiponectin decreased with obesity, both were influenced by pubertal development. Central obesity had an additive effect on leptin levels (above obesity alone). Leptin/adiponectin increased 8.4-fold and 3.2-fold in overweight/obesity, and 15.8- and 4.5-fold with obesity plus MS, in early and late puberty, respectively. Even in normal weight children/adolescents, higher leptin and lower adiponectin concentrations associated with increased risk profile. Conversely, overweight/obese with lower leptin or higher adiponectin concentrations had a less compromised metabolic profile. Conclusion. Leptin, adiponectin, and leptin:adiponectin ratio are informative biomarkers for obesity, central obesity, MS, and abnormal metabolic profile even in normal weight children/adolescents.
Several in vitro studies have suggested the effects of adipokines and insulin resistance on breast cancer cell proliferation and survival. However, little is known about the clinical significance of these findings.
We examined associations between breast cancer recurrence and adiponectin, leptin, insulin resistance, and metabolic syndrome (MetS) in a cohort of 747 patients from 2001 to 2004.
Adjusted hazard ratios showed an inverse trend across the quartiles for serum adiponectin concentration in estrogen receptor (ER)/progesterone receptor (PR) -negative patients (P for trend = 0.027) but not in ER/PR-positive patients. Compared to the highest quartile for adiponectin level, the lowest quartile showed a hazard ratio of 2.82 (1.03 to 7.68). Homeostasis model assessment for insulin resistance (HOMA-IR) showed a positive trend for recurrence in the ER/PR-negative group (P for trend = 0.087) and a negative trend in the ER/PR-positive group (P for trend = 0.081). Leptin did not show any associations (P for trend >0.05). A linear trend was observed with the number of components of MetS in ER/PR-negative patients (P for trend = 0.044). This association disappeared when adjusted for adiponectin and HOMA-IR.
Adiponectin and HOMA-IR have prognostic significance in breast cancer recurrence and interventions related to these factors may protect against recurrence in ER/PR-negative patients. These findings were not observed in the case of ER/PR-positive patients. Further evaluation of these insignificant associations is needed because it might be biased by adjuvant chemotherapy or other confounders.
Leptin and adiponectin represent two newly discovered adipose tissue
derived hormones with important roles in energy homeostasis and insulin
resistance. Their interrelations with the manifestations of the HIV associated
metabolic syndrome and specific somatomorphic changes i.e. fat redistribution is
reviewed. A synopsis of published studies is presented and the potential role of
leptin and adiponectin is discussed. We have described an association of the HIV
metabolic syndrome with a state of reduced insulin sensitivity due to
adiponectin deficiency. The metabolic syndrome is also accompanied by leptin
deficiency in lipoatrophic subjects and possibly by a leptin resistance state in
lipohypertrophic patients. Adiponectin and / or leptin therapy in a manner
similar to other leptin deficiency states may assist in the future management of
HIV; adipokine; adipocytokines; adiponectin; metabolic syndrome; insulin resistance
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.
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
Critically ill patients requiring intensive care uniformly develop insulin resistance. This is most pronounced in patients with sepsis. Recently, several hormones secreted by adipose tissue have been identified to be involved in overall insulin sensitivity in metabolic syndrome-related conditions. However, little is known about these adipokines in critical illness.
We studied circulating levels of the adipokines adiponectin, retinol-binding protein 4 (RBP4), and leptin during critical illness, and the impact of intensive insulin therapy, a therapy shown to affect insulin sensitivity, in serum samples from prolonged critically ill patients with a respiratory critical illness (n = 318). For comparison, we studied healthy subjects (n = 22) and acutely stressed patients (n = 22).
During acute critical illness, circulating levels of adiponectin, RBP4, and leptin were low. Patients with sepsis had lower levels of leptin and RBP4 than did nonseptic patients. When critical illness was sustained, adipokine levels returned to normal reference values. Insulin therapy enhanced adiponectin, blunted the rise of RBP4, and did not alter leptin levels.
Acute critical illness is associated with immediate, but transiently low serum adipokine levels. Adiponectin and RBP4 are associated with altered insulin resistance in critical illness.
Ethnic differences in adipose tissue distribution may contribute to different chronic disease risks across ethnic groups, and adipokines may mediate the risk. In a cross-sectional study, we examined ethnic differences in adipokines and inflammatory markers as related to body mass index (BMI) among 183 premenopausal women with Caucasian and Asian ancestry. General linear models were used to estimate adjusted mean levels of leptin, adiponectin, interleukin-6, and C-reactive protein (CRP). Asian women had significantly lower serum levels of leptin, adiponectin, and CRP than Caucasian participants (P ≤ .01) across all levels of BMI. Among overweight and obese women, Asians showed a stronger association of CRP with leptin (β = 1.34 versus β = 0.64) and with adiponectin (β = −0.95 versus β = −0.75) than Caucasians. Compared to Caucasians of similar BMI, Asians may experience a higher chronic disease risk due to lower levels of adiponectin despite their lower levels of leptin.
Background and Objectives
Adiponectin is an adipose tissue-derived hormone that has beneficial effects on cardiac function and has been reported to be associated with lipid metabolism, glucose metabolism, and insulin resistance. Serum levels of adiponectin are reduced in obese individuals compared with non-obese individuals. Obesity is associated with an increased incidence of atrial fibrillation (AF); however, the role of adiponectin in AF is unclear. The aim of this study is to evaluate the relationship between the plasma adiponectin level and AF.
Subjects and Methods
Sixty-one consecutive patients were prospectively enrolled for this study. Subjects were divided into two groups: patients with AF (n=30) and controls (n=31). Laboratory evaluation, including levels of plasma adiponectin, was performed and echocardiographic parameters were measured.
The baseline characteristics were not different between the two groups. The plasma adiponectin level of patients in the AF group was significantly lower than in the control group (14.9±7.2 vs. 19.±8.9 µg/mL, p<0.05). In addition, when we divided the AF patients into paroxysmal and chronic AF, the plasma adiponectin level was significantly lower in patients with paroxysmal AF, compared with the control group. In multiple binary logistic regression analysis to evaluate the independent predictors for AF, adiponectin and left atrial diameter were strong independent predictors of AF.
In this study a lower plasma adiponectin concentration was significantly associated with that of paroxysmal AF. Hypoadiponectinemia can potentially be an important risk factor for AF.
Adiponectin; Atrial fibrillation
Prevalence of Type 2 diabetes mellitus among Sudanese population was found to be 3.4% and associated with high rates of complications and obesity. Different adipocytokines are secreted from adipose tissues, among them adiponectin, which was shown to have insulins ensitizing properties and anti-inflammatory, anti-atherogenic effect. The aim of this study was to characterize type 2 diabetes in Sudanese diabetic subjects and controls in respect to hormones influencing or influenced by glucose metabolism.
104 type 2 diabetic patients (45 men and 59 women), and 75 matched control subjects (34 men and 41 women) were studied. Fasting serum samples were used to measure adiponectin, leptin, insulin, proinsulin, ghrelin and glucose. Body mass index, insulin/proinsulin ratio and (HOMA) insulin resistance and beta cell function were also calculated.
Adiponectin serum concentrations were significantly lower in subjects with type 2 diabetes compared with controls subjects (P = 0.002), comparison between males and females did not reach significant levels in both diabetic (P = 0.06) or controls (P = 0.16) groups. In the diabetic group adiponectin correlated positively with serum glucose, negatively with serum proinsulin and HOMA beta cell function (P = 0.03) respectively and serum ghrelin (P = 0.003), but not with BMI, HOMA insulin resistance, insulin or leptin. In controls serum adiponectin correlated negatively with BMI (P = 0.002) but not with other variables.
The findings of this study suggest that, adiponectin concentrations independent on BMI as a measure of adiposity, were mostly linked to insulin sensitivity and not to insulin resistance in Sudanese type 2 diabetic subjects, where race specific regulation mechanisms or different type 2 diabetes phenotype suggested being a major contributory factor in clarification the findings of this study.
Diabetes mellitus; Sudan; Adiponectin; Ghrelin; Leptin
Leptin and adiponectin are two hormones, which are released from adipocytes in order to control energy expenditure. Both hormones are also involved in glucose homeostasis through control of insulin secretion from pancreatic islets. Since Pdx1, PPARγ, and foxm1 play important roles in islets function, it is essential to understand how these genes are regulated in the islets of Langerhans.
We have designed an experiment to identify the effect of leptin and adiponectin treatment on Pdx1, PPARγ, and foxm1 transcription.
Materials and Methods
Islets were isolated from adult male rats by collagenase and incubated with different concentrations of leptin and adiponectin for 24 hours. Next, by means of real time PCR, we evaluated the gene transcription related to a housekeeping gene. The effect of leptin and adiponectin on insulin secretion was evaluated by ELISA.
Leptin decreased PPARγ transcription and insulin secretion, while adiponectin significantly increased Pdx1 and PPARγ transcription and insulin secretion in rat islets. The transcription of foxm1 did not change in the islet cells treated with leptin or adiponectin.
These findings indicate the possibility that Pdx1 and PPARγ transcription is a mediator of leptin and adiponectin function in control of insulin secretion and glucose homeostasis in pancreatic islets.
Leptin, Adiponectin; PPAR gamma; Islets of Langerhans; Insulin
Body weight is positively associated with bone mineral density but the relationship between obesity and bone mineral density is unclear. Leptin and adiponectin are potential independent contributors to bone mineral density. We assessed the correlations of body composition, leptin and adiponectin with bone mineral density, and whether leptin, adiponectin and body composition determine bone mineral density independently in prepubertal girls. Forty-eight prepubertal girls were classified into obese and control groups by body mass index. Serum leptin and adiponectin levels were determined by enzyme immunoassay. Bone mineral density was measured using dual energy radiography absorptiometry and body composition was measured using bioelectrical impedance analysis. Lean and fat mass, and leptin were positively correlated with bone mineral density. Lean mass was a positive independent predictor of femoral and L-spine bone mineral density. Serum leptin was a postivie independent predictor of femoral bone mineral density. Fat mass was a negative independent predictor of femoral bone mineral density. In prepubertal girls, lean mass has a favorable effect on bone mineral density. Fat mass seems not to protect the bone structure against osteoporosis, despite increased mechanical loading. Serum leptin may play a biological role in regulating bone metabolism.
Bone Density; Body Composition; Leptin; Adiponectin; Obesity
The aim of this study was to investigate the relationship among plasma leptin, ghrelin, adiponectin, resistin levels, and obstructive sleep apnea syndrome (OSAS).
Fifty-five consecutive newly diagnosed OSAS patients and 15 age-matched nonapneic controls were enrolled in this study. After sleep study between 8:00 AM and 9:00 AM on the morning, venous blood was obtained in the fasting state to measure ghrelin and adipokines.
Serum ghrelin levels of OSAS group were significantly (P < 0.05) higher than those of the control group. No significant difference was noted in the levels of leptin, adiponectin, and resistin in OSAS group when compared to controls. There was a significant positive correlation between ghrelin and apnea–hypopnea index (AHI) (r = 0.237, P < 0.05) or the Epworth sleepiness scale (ESS) (r = 0.28, P < 0.05). There was also a significant positive correlation between leptin and body mass index (r = 0.592, P < 0.0001). No significant correlation was observed between leptin, adiponectin, resistin, and any polysomnographic parameters.
Our findings demonstrated that serum ghrelin levels were higher in OSAS patients than those of control group and correlated with AHI and ESS. Further studies are needed to clarify the complex relation among OSAS, obesity, adipokines, and ghrelin.
Adipokines; obesity; sleep apnea
Elevated concentrations of adiponectin are associated with a favorable metabolic profile but also with adverse cardiovascular outcomes. This apparent discrepancy has raised questions about whether adiponectin is associated with an increased or decreased risk of coronary heart disease (CHD). We sought to determine whether higher adiponectin levels are associated with exercise-induced ischemia in patients with stable CHD.
Methods and results
We measured total serum adiponectin concentrations and evaluated exercise-induced ischemia by stress echocardiography in a cross-sectional study of 899 outpatients with documented stable CHD. Of these, 217 (24%) had inducible ischemia. Although adiponectin levels correlated negatively with diabetes prevalence, body mass index, serum insulin, fasting glucose, low-density lipoprotein cholesterol, and triglycerides and positively with high-density lipoprotein cholesterol (all P< 0.005), elevated adiponectin concentrations were also associated with a greater risk of inducible ischemia. Each standard deviation (0.08 μg/mL) increase in log adiponectin was associated with a 35% greater odds of inducible ischemia (unadjusted odds ratio 1.35; 95% confidence interval 1.15–1.57; P=0.0002). Although attenuated, this association remained present after multivariable adjustment for traditional cardiovascular risk factors and other measures of cardiac function (adjusted odds ratio 1.21; 95% confidence interval 1.02–1.43; P=0.03).
Elevated concentrations of adiponectin are independently associated with inducible ischemia in patients with stable CHD. These findings raise the possibility that the presence of chronic inducible ischemia may alter the cardio-protective effects afforded by adiponectin secretion in the healthy population.
Adiponectin; Coronary heart disease (CHD); Ischemia; Adipokine; Reverse epidemiology
Polycystic ovarian syndrome (PCOS) is frequently characterized by obesity and metabolic diseases including hypertension, insulin resistance, and diabetes in adulthood, all leading to an increased risk of atherosclerosis. The present study aimed to evaluate serum and production of inflammatory markers in adolescent Sardinian PCOS. On the basis of HOMA findings, patients were divided into noninsulin resistant (NIR) and insulin resistant (IR), and were weight- and age-matched with healthy girls. Inflammatory cytokines (TNF-α, IL-6, Il-10, TGF-β) and lipokines (leptin, adiponectin), the reactant hs-CRP, and in vitro inflammatory lympho-monocyte response to microbial stimulus were evaluated. In healthy and PCOS subjects, leptin and hs-CRP were correlated with BMI, whereas adiponectin was significantly reduced in all PCOS groups. Although cytokines were similar in all groups, Interleukin-6 (IL-6) was significantly higher in IR PCOS. Moreover, in the latter group lipopolysaccharide-activated monocytes secreted significantly higher levels of IL-6 compared to NIR and control subjects. To conclude, IR PCOS displayed increased IL-6 serum levels and higher secretion in LPS-activated monocytes, whilst revealing no differences for other inflammatory cytokines. These results suggest that in PCOS patients an altered immune response to inflammatory stimuli is present in IR, likely contributing towards determining onset of a low grade inflammation.