Adipocytokine Concentrations Research Articles

Association of Polymorphisms Modulating Low-density Lipoprotein Cholesterol with Susceptibility, Severity, and Progression of Rheumatoid Arthritis

Dyslipidemia, a risk factor for cardiovascular diseases, is more prevalent in patients with rheumatoid arthritis (RA) than in the general population. We investigated whether single-nucleotide polymorphisms (SNP) modulating low-density lipoprotein (LDL) cholesterol affect susceptibility, severity, and progression of RA. We enrolled 302 patients with RA and 1636 healthy controls, and investigated the SNP modulating LDL cholesterol. Clinical characteristics of RA, serum adipocytokine concentrations, and radiographic severity were analyzed according to genotype score based on the number of unfavorable alleles. The influence of genotype score on radiographic progression was also investigated using multivariable logistic models. We identified 3 SNP (rs688, rs693, and rs4420638) modulating LDL cholesterol in Koreans, which correlated well with LDL cholesterol levels in both patients with RA and controls. Among them, 2 SNP, rs688 and rs4420638, were more prevalent in patients with RA than in controls. In patients with RA carrying more unfavorable alleles (genotype score ≥ 3), disease activity measures, serum adipocytokine levels, and radiographic severity were all increased. The genotype score was an independent risk factor for radiographic progression of RA over 2 years, and its effect was greater than the influence of conventional risk factors. SNP modulating LDL cholesterol influence the risk, activity, and severity of RA. These results provide the first evidence that genetic mechanisms linked to dyslipidemia may directly contribute to the susceptibility and prognosis of RA, a representative of chronic inflammatory diseases, explaining the high incidence of dyslipidemia in RA.

Relationships between maternal novel adipocytokines and bone biomarkers in complicated by gestational hypertensive disorders and normal pregnancies

Objective: To investigate possible associations of the novel adipocytokines resistin, apelin and visfatin (implicated in the complex control of bone biology) with several biochemical determinants of bone turnover in maternal blood from normal pregnancies and pregnancies complicated by gestational hypertensive disorders (preeclampsia or pregnancy-induced hypertension).Methods: Circulating maternal concentrations of resistin, apelin and visfatin were correlated with circulating markers of bone formation [osteocalcin (OC), bone-specific alkaline phosphatase (BALP)] and resorption [osteoprotegerin (OPG), soluble receptor activator of nuclear factor-κB ligand (sRANKL) and cross-linked N-telopeptide of type I collagen (NTx)] in full-term pregnancies (20 normal and 20 complicated by gestational hypertensive disorders).Results: In normal pregnancies, no correlation was recorded between maternal concentrations of adipocytokines and the above bone biomarkers. In pregnancies with gestational hypertensive disorders, maternal apelin concentrations negatively correlated with NTx ones (r = −0.489, p = 0.034), while maternal visfatin concentrations positively correlated with OPG ones (r = 0.464, p = 0.039).Conclusions: No associations were found between maternal concentrations of all three studied adipocytokines and respective concentrations of bone biomarkers in normal pregnancies. By contrast, in pregnancies with gestational hypertensive disorders, maternal concentrations of apelin and visfatin correlated with respective concentrations of indices of bone turnover. Further prospective studies are needed to clarify these relationships.

Correlation of Resistin with Inflammatory and Cardiometabolic Markers in Obese Adolescents with and without Metabolic Syndrome

Objective: The link between plasma resistin and obesity-related cardiometabolic disorders in children remains debatable. This study assessed the relationships of plasma resistin with cardiovascular risk factors, pro-inflammatory markers and insulin resistance index (HOMA-IR) in obese (Ob) adolescents and obese adolescents with metabolic syndrome (Ob-MS) compared to healthy controls (CO). Methods: 114 obese adolescents (60 Ob, age 13.6 ± 0.9 years, BMI 28.0 ± 2.2 kg/m², and 54 Ob-MS, age 13.8 ± 1.0 years, BMI 32.5 ± 4.8 kg/m²) and 37 CO (age 13.7 ± 0.8 years, BMI 22.8 ± 0.8 kg/m²) were studied. Anthropometrics, cardiac variables as well as fasting plasma concentrations of lipids, glucose, insulin, and adipocytokines (resistin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP)) were measured. HOMA-IR was calculated, and the presence of MS was assessed. Results: Plasma resistin was significantly higher in Ob-MS than in both Ob and CO and was correlated with anthropometric, cardiovascular, pro-inflammatory markers and several components of MS as was HOMA-IR in Ob and Ob-MS. With increasing the number of MS components, plasma resistin, pro-inflammatory markers, and HOMA-IR were also increased. Multiple regression models highlighted significant correlation between resistin and both HOMA-IR (r = 0.40, p < 0.05) and systolic blood pressure (r = 0.63, p < 0.01) in Ob-MS. Conclusion: These results support the hypothesis that there is an association between circulating resistin and childhood obesity-related inflammatory and cardiometabolic events.

Adipocytokine Associations with Insulin Resistance in British South Asians

Aims. Adipocytokines are implicated in the pathogenesis of type 2 diabetes and may represent identifiable precursors of metabolic disease within high-risk groups. We investigated adiponectin, leptin, and TNF-α and assessed the contribution of these molecules to insulin resistance in south Asians. Hypothesis. South Asians have adverse adipocytokine profiles which associate with an HOMA-derived insulin resistance phenotype. Methods. We measured adipocytokine concentrations in south Asians with newly diagnosed impaired glucose tolerance or Type 2 Diabetes Mellitus in a case-control study. 158 (48.5% males) volunteers aged 25–75 years with risk factors for diabetes but no known vascular or metabolic disease provided serum samples for ELISA and bioplex assays. Results. Total adiponectin concentration progressively decreased across the glucose spectrum in both sexes. A reciprocal trend in leptin concentration was observed only in south Asian men. Adiponectin but not leptin independently associated with HOMA-derived insulin resistance after logistic multivariate regression. Conclusion. Diasporic south Asian populations have an adverse adipocytokine profile which deteriorates further with glucose dysregulation. Insulin resistance is inversely associated with adiponectin independent of BMI and waist circumference in south Asians, implying that adipocytokine interplay contributes to the pathogenesis of metabolic disease in this group.

Serum adiponectin concentration in patients with type 1 diabetes

Adiponectin (AdipoQ) is known as one of the major mediators of adipose tissue metabolism with beneficial effects on carbohydrates and lipids. The effect of low concentrations of adiponectin on the development of obesity, insulin resistance, type 2 diabetes and cardiovascular disease is quite well understood. However, there is still little research available defining the role of adiponectin in the pathogenesis of type 1 diabetes (DM1) and its’ complications. Therefore, it seems appropriate to undertake research aiming to evaluate serum levels of adiponectin in the blood of patients with DM1 and to evaluate the correlations between this adipocytokine concentration and selected clinical data as well as biochemical parameters evaluated in routine diagnosis and monitoring of diabetes. The study included 40 patients aged 41.9±12.7 years, diagnosed with type 1 diabetes and group of healthy controls (n=26) with mean age of 41.2±15.3 years. In serum samples of all patients single-time determination of adiponectin, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, urea, creatinine, glycated hemoglobin levels and alanine aminotransferase and aspartate aminotransferase activity were performed. The mean AdipoQ concentration was significantly higher in the study group than in healthy subjects (16.2±11.7 ug/ml vs. 7.3±2.0 ug/ml; p&lt;0.001). Significantly higher levels of AdipoQ in women than in men with DM1 (23.1±14.0 ug/ml vs. 11.0±5.8 ug/ml; p&lt;0.001) were found. AdipoQ was directly correlated with disease duration (r=0.539, p=0.003) as well as inversely with patients’ body mass (r=-0.423, p=0.025). Observed increased levels of AdipoQ in patients with DM1 with concomitant vascular complications as compared to patients without the complications, however not statistically significant, suggests that this protein may play important role in the pathogenesis of diabetic angiopathy.

Changed adipocytokine concentrations in colorectal tumor patients and morbidly obese patients compared to healthy controls

BackgroundObesity has been associated with increased incidence of colorectal cancer. Adipose tissue dysfunction accompanied with alterations in the release of adipocytokines has been proposed to contribute to cancer pathogenesis and progression. The aim of this study was to analyze plasma concentrations of several adipose tissue expressed hormones in colorectal cancer patients (CRC) and morbidly obese (MO) patients and to compare these concentrations to clinicopathological parameters.MethodsPlasma concentrations of adiponectin, resistin, leptin, active plasminogen activator inhibitor (PAI)-1, monocyte chemotactic protein (MCP)-1, interleukin (IL)-1 alpha, and tumor necrosis factor (TNF)-alpha were determined in 67 patients operated on for CRC (31 rectal cancers, 36 colon cancers), 37 patients operated on for morbid obesity and 60 healthy blood donors (BD).ResultsCompared to BD, leptin concentrations were lowered in CRC patients whereas those of MO patients were elevated. Adiponectin concentrations were only lowered in MO patients. Concentrations of MCP-1, PAI-1, and IL-1 alpha were elevated in both CRC and MO patients, while resistin and TNF-alpha were similarly expressed in MO and CRC patients compared to BD. Resistin concentrations positively correlated with tumor staging (p<0.002) and grading (p=0.015) of rectal tumor patients.ConclusionsThe results suggest that both MO and CRC have low-grade inflammation as part of their etiology.

The influence of sodium- and calcium-regulatory hormone interventions on adipocytokines in obesity and diabetes

ObjectiveThe renin–angiotensin–aldosterone system (RAAS), vitamin D, and parathyroid hormone have all been implicated as regulators of adipocytokines and inflammation. We evaluated human interventional study protocols to investigate whether controlled modulations of these calcium- and sodium-regulatory hormones could influence adipocytokines and inflammation in obesity and diabetes. MethodsPost-hoc analyses of two separate human protocols (Protocol 1, n=14; Protocol 2, n=24) conducted in a clinical research setting after rigorous control of diet, posture, medications, and diurnal rhythm, were performed. Protocol 1 evaluated obese hypertensives with vitamin D deficiency who received an infusion of angiotensin II (AngII) before and after 1month of vitamin D3 therapy. Protocol 2 evaluated obese subjects with type 2 diabetes who also received AngII. Adipocytokines and inflammatory markers were measured before and after vitamin D3 therapy, and also before and after infusions of AngII. ResultsVitamin D3 therapy significantly raised 25(OH)D and 1,25(OH)2D concentrations, and lowered parathyroid hormone, but had no effect on concentrations of adiponectin, resistin, leptin, IL-6, PAI-1, urinary TGFβ1, or HOMA-IR. AngII infusions, despite significant elevations in blood pressure and serum aldosterone, did not influence adipocytokine concentrations in either protocol. ConclusionIn contrast to prior studies conducted in healthy populations, or those that could not control major regulators of the RAAS or adipocytokines, we observed that robust modulations in calcium- and sodium-regulatory hormones did not influence adipocytokines or inflammation in obesity or diabetes. Adipose-tissue physiology in these conditions may alter the hormonal regulation of inflammatory parameters.

Association of body mass index, sagittal abdominal diameter and waist-hip ratio with cardiometabolic risk factors and adipocytokines in Arab children and adolescents

BackgroundSagittal abdominal diameter (SAD) is a novel anthropometric measure hypothesized to be a surrogate measure of visceral abdominal obesity in adults. This study aims to determine whether SAD is superior to other anthropometric measures such as body mass index (BMI) and waist to hip ratio (WHR) in terms of association to cardiometabolic risk and circulating adipocytokine concentrations in a cohort of Saudi children and adolescents.MethodsA total of 948 (495 boys and 453 girls) apparently healthy children with varying BMI, aged 10–17 years, were included in this cross sectional study. Fasting glucose, lipid profile, leptin, adiponectin, resistin, insulin, TNF-α and aPAI-1 were measured in serum and HOMA-IR was calculated. MetS components were defined according to the International Diabetes Federation (IDF) criteria.ResultsBMI was superior to SAD as well as WHR, and had the highest number of significant associations to MetS components and adipocytokines even after adjustment for age and gender, including blood pressure, lipids, glucose and leptin.ConclusionIn conclusion, while SAD is significantly associated with components of MetS among children and adolescents, it is not superior to BMI. The use of SAD therefore may not be practical for use in the pediatric clinical setting. Follow-up studies are needed to determine whether SAD has clinical significance in terms of harder outcomes such as predicting diabetes mellitus or cardiovascular diseases.

Adipocytokines and Insulin Resistance across Various Degrees of Glucose Tolerance in Pregnancy

Gestational diabetes mellitus is characterized by progressive insulin resistance. Adipocytokines are thought to be associated with insulin resistance. This cross-sectional study evaluated the associations between serum concentrations of several adipocytokines and insulin resistance at different stages of glucose tolerance in pregnancy, using the homeostasis model assessment of insulin resistance (HOMA-IR) as a reference. According to oral glucose tolerance test results, 74 pregnant women were divided into three groups: normal glucose tolerance (n = 25); intermediate glucose tolerance (n = 19); gestational diabetes mellitus (n = 30). Adiponectin, leptin, resistin, visfatin and retinol-binding protein 4 (RBP4) concentrations were measured using enzyme-linked immuno sorbent assays. Groups were comparable regarding age, week of gestation and body mass index before gestation. There were statistically significant between-group differences in HOMA-IR, but no significant differences regarding serum adipocytokine concentrations. Adipo nectin, leptin, resistin, visfatin and RBP4 were not associated with the degree of glucose tolerance in pregnancy. Concentrations of these adipocytokines are not sufficiently sensitive to replace HOMA- IR in pregnancy.

Serum Concentrations of Resistin and Adiponectin and Their Relationship to Insulin Resistance in Subjects with Impaired Glucose Tolerance

This study measured the serum concentrations of resistin and adiponectin in Chinese subjects with impaired glucose tolerance (IGT) and investigated their association with insulin resistance, metabolic parameters and circulating inflammatory markers. A total of 124 subjects participated in the study (44 with IGT and 80 with normal glucose tolerance [NGT]). Fasting serum concentrations of lipids, glucose, insulin and adipocytokines (resistin, adiponectin, leptin, tumour necrosis factor-α [TNF-α], interleukin-6 and C-reactive protein) were measured. Serum resistin concentrations were similar in the IGT and NGT groups but were significantly higher in overweight/ obese IGT subjects than in those of normal weight. Serum adiponectin concentrations were significantly lower in the IGT group than in the NGT group. In the IGT group, resistin was positively correlated with age, body mass index and TNF-α, and adiponectin was correlated positively with high-density lipoprotein cholesterol and negatively with TNF-α and waist/hip ratio. Circulating resistin is unlikely to be a major mediator of glucose tolerance in humans but it may have an inflammatory role in IGT. The data support the theory that circulating adiponectin has an anti-inflammatory and anti-insulin resistance function.

MRNA expression of adipocytokines and glucocorticoid-related genes are associated with downregulation of E-cadherin mRNA in colorectal adenocarcinomas

There is a consistently reported relationship between the incidence of colon cancer and obesity. It is thought that adipose tissue, particularly visceral fat, which secretes systemic factors that alter immunological, metabolic and endocrine milieu and promotes insulin resistance by producing adipocytokines, is important in cancer progression. Systemic high concentrations of adipocytokines, such as tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and glucocorticoid metabolism-related genes have been associated with gastrointestinal cancer. However, limited information exists about the expression of these cytokines within tumour tissue. mRNA expression of TNF-α, IL-6,IL-8, IL-10, IL-1RN, glucocorticoid receptor alpha (GR-α), 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), plasminogen activator inhibitor-1 (PAI-1), Slug, vimentin, Snail and E-cadherin was analysed in paired samples of tumour tissue and normal mucosa in 60 surgical patients for Dukes B and C colorectal adenocarcinomas using quantitative reverse transcription PCR and microarray technology. The mRNA expression level of analysed genes was compared between tumour tissue and normal mucosa from the same patients, and a correlation to mRNA expression of E-cadherin in the same tissue samples was also performed. A highly significant difference in mRNA expression level of several of the analysed genes was observed between tumour tissue and the normal intestinal mucosa. Inverse correlation between mRNA expression of 11βHSD1, IL-6, GR-α and PAI-1 on one hand and mRNA expression of E-cadherin on the other hand was observed. Results show that the adipocytokines and glucocorticoid metabolism-related genes are overexpressed in colorectal adenocarcinomas, and expression of these genes is associated with the downregulation of E-cadherin mRNA, connecting these genes to carcinogenesis and progression of colorectal cancer.

Association of serum adipocytokine levels with cardiac autonomic neuropathy in type 2 diabetic patients

BackgroundCardiac 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.MethodsA 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.ResultsAlthough, 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).ConclusionsIn 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.

Effect of vitamin A deficiency on the immune response in obesity

Obesity has been associated with low-grade systemic inflammation and with micronutrient deficiencies. Obese individuals have been found to have lower vitamin A levels and lower vitamin A intake compared with normal-weight individuals. Vitamin A plays a major role in the immune function, including innate immunity, cell-mediated immunity and humoral antibody immunity. It has also been recognised recently that vitamin A has important regulatory functions. Vitamin A status has an important effect on the chronic inflammatory response. Vitamin A deficiency increases a T-helper type 1 (Th1) response, elevates levels of pro-inflammatory cytokines, increases the expression of leptin, resistin and uncoupling proteins (UCP) and promotes adipogenesis. The effect of vitamin A deficiency on obesity might be increasing the risk of fat deposition and also the risk of chronic inflammation associated with obesity. Supplementation with vitamin A in vitro and in animal models has been found to reduce concentrations of adipocytokines, such as leptin and resistin. In conclusion, vitamin A deficiency increases a Th1 response in the presence of obesity and thus, increases the inflammatory process involved in chronic inflammation and fat deposition. The metabolism of leptin and other adipocytokines may play a critical role in the effect of vitamin A deficiency in the inflammatory response observed in obesity.

Serum sphingolipids and inflammatory mediators in adolescents at risk for metabolic syndrome

The purpose of this study was to determine low-grade inflammation associated with obesity that is mediated partially by TNF-α, an adipocytokine which stimulates sphingomyelinase activity in adipocytes. Circulating ceramide (Cer) and sphingosine 1-phosphate (S1P) are elevated in genetically obese (ob/ob) mice. We aimed to determine whether serum sphingolipid concentrations correlate with measures of obesity, insulin resistance, and lipid profiles in overweight versus lean adolescents. This cross-sectional study recruited 30 healthy overweight (body mass index, BMI≥85%) and 15 lean (BMI 10-84%) adolescents. Anthropometric measurements and fasting blood samples were collected at one clinic visit. Serum glucose, insulin, and fasting lipid profiles were measured. Serum adipocytokine concentrations were measured by ELISA or colorimetric assay and sphingolipids were measured by HPLC-mass spectrometry. Between group differences in serum sphingolipid concentrations were assessed. Correlations between sphingolipid concentrations and (i) body mass index, (ii) calculated homeostasis model assessment of insulin resistance (HOMA-IR), (iii) adipocytokines, and (iv) lipoproteins were determined. The results showed that significant differences in HOMA-IR (4.5±3.2 vs. 1.2±0.7), free fatty acids (0.8±0.3mmol/l vs. 0.4±0.3mmol/l), and adiponectin (6.4±3.8 vs. 12.6±9.9 μg/ml) were seen between groups (overweight vs. lean). There were significant correlations between Cer and TNF-α (r=0.429), S1P and TNF-α (r=0.288), Cer and adiponectin (r=0.321), Cer:S1P and adiponectin (r=0.324), Cer and HOMA-IR (r=0.307), and Cer:S1P and LDL cholesterol (r=0.453); these associations persisted after adjustment for BMI Z-score, sex, and Tanner stage. We concluded that elevated sphingolipid concentrations correlate with TNF-α, adiponectin, lipoprotein profiles, and HOMA-IR. Ceramide is associated with atherogenic lipid profiles and the development of insulin resistance in obese adolescents, similar to adults.

Evaluation of the relationship between leptin, resistin, adiponectin and natural regulatory T cells in relapsing-remitting multiple sclerosis

Background and purposeData suggest that adipocytokines and natural regulatory T (nTreg) cells play a pivotal role in the immunopathogenesis of multiple sclerosis and the associated inflammation. The purpose of this study was to evaluate selected adipocytokines and nTreg cells and to assess their relationship with relapsing-remitting multiple sclerosis (RRMS). Material and methodsThe study was conducted among 25 patients with RRMS and 25 healthy individuals. Blood samples were collected within two weeks after the beginning of acute relapse of RRMS. The body mass index (BMI) of each patient was calculated. Serum adipocytokine concentrations were determined by ELISA and nTreg cells were evaluated using multicolour flow cytometry. ResultsPatients and controls had similar BMI, regardless of gender. Significantly higher leptin and resistin levels and significantly lower adiponectin levels were found in patients with RRMS in comparison to the control group (p < 0.0001). The percentage of nTreg cells (p < 0.01) and the mean fluorescence channel (MFC) of FoxP3 were significantly reduced in patients with RRMS (p < 0.001). There was an inverse correlation between leptin concentration and MFC of the transcription factor Foxp3 nTreg in patients with RRMS (r = −0.7, p < 0.05). ConclusionsProinflammatory adipocytokine profile and decreased percentage of nTreg cells suggest their implication in the inflammatory response in RRMS regardless of corticosteroid therapy. The correlation between leptin and the MFC of the transcription factor Foxp3 in nTreg cells in patients with RRMS suggests its inhibitory effect on FoxP3 expression.

Comparison of rheumatoid articular adipose and synovial tissue reactivity to proinflammatory stimuli: contribution to adipocytokine network

Objectives(1) To compare spontaneous and stimuli-induced adipocytokine secretion by articular adipose tissue (AAT) and synovial membrane (SM) explants obtained from patients with rheumatoid arthritis (RA). (2) To investigate the biological...

Plasma adipocytokine and ghrelin levels in relation to bone mineral density in prepubertal rhythmic gymnasts

The aim of the present study was to investigate possible differences in plasma adipocytokine and ghrelin levels and body composition parameters in prepubertal rhythmic gymnasts (RG) and untrained controls (UC), and to examine the relationships of bone mineral density (BMD) with hormonal status in prepubertal children with different physical activity patterns. Eighty-nine 7- to 9-year-old girls participated in the study (RG, n = 46; UC, n = 43). Body composition and BMD were measured by dual-energy X-ray absorptiometry. Bone maturity was estimated by using a radiograph of the nondominant hand. The measured whole-body, lumbar spine (LS), and femoral neck (FN) BMD values were significantly higher (P < 0.05) in gymnasts than in controls. In addition, RG presented significantly lower and higher values (P < 0.05) for leptin and ghrelin concentrations, respectively, in comparison with UC. No differences were observed for adiponectin levels between the studied groups. No relationships between measured BMD values with leptin and ghrelin were observed even after adjustment for age and fat mass (FM) in RG. Whole-body and LS BMD values were significantly correlated with leptin after controlling for age and FM (r = 0.32, P < 0.05) in UC. Femoral neck BMD remained significantly correlated with ghrelin after adjusting for age and FM (r = -0.4, P < 0.05) in UC. No relationships were found between measured BMD values and adiponectin even after controlling for age and FM values in both groups. In conclusion, although all measured BMD values were significantly higher in RG, plasma adipocytokine and ghrelin concentrations were not directly related to bone mineralization in prepubertal RG in contrast to UC.

Postprandial activation of protein kinase C� regulates the expression of adipocytokines via the transcription factor AP-2β

Abnormal secretion of adipocytokines promotes atherosclerosis, diabetes and insulin resistance, and is mainly induced by adipocyte hypertrophy. Recently, the circulating adipocytokine concentrations were reported to change in the postprandial period, as the levels of TNFα, IL-6 IL-8 and MCP-1 increased after a meal, whereas that of adiponectin decreased. These data suggest that prandial modulation of cytokines may be involved in the pathogenesis of atherosclerosis in type 2 diabetes. However, the regulatory mechanism of such change is still unclear. In the present study, we identified this mechanism with a special focus on the functions of protein kinase C (PKC) and of the transcription factor AP-2β, both of which are associated with the pathophysiology of adipocytokine regulation. PKCµ was highly phosphorylated in the re-feeding condition compared to the fasting condition in mouse adipose tissue, while other PKC isoforms remained unchanged. Furthermore, overexpression of PKCµ in 3T3-L1 adipocytes, but not other PKC isoforms, positively regulated the mRNA expression and promoter activity of MCP-1 and IL-6, and negatively regulated those of adiponectin. AP-2β had similar effects on the expression and promoter activity of these adipocytokines. Interestingly, overexpression of PKCµ enhanced the stimulatory and inhibitory effects of AP-2β on the expression of these adipocytokines. Finally, PKCµ could not activate a mutant MCP-1 promoter lacking the AP-2β binding domain. Our results suggest that postprandial activation of PKCµ plays a role in disordered postprandial adipocytokine expression through AP-2β.

Circulating adipocytokines in morbid obese patients, relation with cardiovascular risk factors and anthropometric parameters.

Obesity and insulin resistance are associated with cardiovascular risk factors, including adipocytokines. The aim of the present study was to explore the relation of circulating adipocytokines with cardiovascular risk and anthropometric parameters in morbid obese patients. A population of 65 morbid obese patients was analyzed in a prospective way. A biochemical, anthropometric and dietary evaluation was realized. In the multivariate analysis with resistin as dependent variable, the BMI remained in the model (F = 16.6; p < 0.05), with an increase of 0.23 (CI 95%: 0.06-0.41) ng/ml with each point of BMI. In a second model with adiponectin as dependent variable, the age remained in the model (F = 4.46; p < 0.05), with an increase of 3.62 (CI 95%: 0.05-7.21) ng/ml with each year. In the third model with interleukin 6 as dependent variable, the HOMA, CRP and weight remained in the model (F = 8.8; p < 0.01), with an increase of 0.26 (CI 95%: 0.05-0.47) pg/ml with each point of HOMA, an increase of 0.43 (CI 95%: 0.10-0.76) pg/ml with each 1 mg/dl of CRP and an increase of 0.13 (CI 95%: 0.05-0.21) pg/ml with each kg of weight. In the fourth model with TNF-alpha as dependent variable, resistin, IL-6 and weight remained in the model (F = 5.2; p < 0.01), with an increase of 1.49 (CI 95%: 0.46-2.53) pg/ml with each point of resistin, an increase of 1.20 (CI 95%: 0.38-2.10) pg/ml with each 1 pg/dl of IL-6 and an increase of 0.27 (CI 95%: 0.04-0.51) pg/ml with each kg of weight. In the fifth model with leptin as dependent variable, BMI and TNF-alpha remained in the model (F = 4.1; p < 0.01), with an increase of 10.35 (CI 95%: 4.10-21.12) ng/ml with each point of BMI and a decrease of 10.16 (CI 95%: -20.37-0.76) pg/ml with each 1 pg/dl of TNF-alpha. Circulating adipocytokine concentrations are associated with different cardiovascular risk factors and anthropometric variables in morbid obese patients.

Disruption of TBP-2 ameliorates insulin sensitivity and secretion without affecting obesity

Type 2 diabetes mellitus (T2DM) is characterized by defects in both insulin sensitivity and glucose-stimulated insulin secretion (GSIS) and is often accompanied by obesity. In this study, we show that disruption of thioredoxin binding protein-2 (TBP-2, also called Txnip) in obese mice (ob/ob) dramatically improves hyperglycaemia and glucose intolerance, without affecting obesity or adipocytokine concentrations. TBP-2-deficient ob/ob mice exhibited enhanced insulin sensitivity with activated insulin receptor substrate-1/Akt signalling in skeletal muscle and GSIS in islets compared with ob/ob mice. The elevation of uncoupling protein-2 (UCP-2) expression in ob/ob islets was downregulated by TBP-2 deficiency. TBP-2 overexpression suppressed glucose-induced adenosine triphosphate production, Ca2+ influx and GSIS. In β-cells, TBP-2 enhanced the expression level and transcriptional activity of UCP-2 by recruitment of peroxisome proliferator-activated receptor-γ co-activator-1α to the UCP-2 promoter. Thus, TBP-2 is a key regulatory molecule of both insulin sensitivity and GSIS in diabetes, raising the possibility that inhibition of TBP-2 may be a novel therapeutic approach for T2DM.