Influence Of Adiponectin Research Articles

The Influence of Adiponectin on Transport of Low-Density Lipoproteins through Human Endothelial Cell Monolayer In Vitro.

The influence of adiponectin, a protein secreted by adipocytes, on the activation of transendothelial LDL transport, the initial event of atherogenesis, was studied. The addition of adiponectin to the cultured endothelial hybridoma EA.hy926 cells did not affect both basal and TNF-stimulated transendothelial transport of LDL. In addition, adiponectin affects neither expression levels of CAV1, SCARB1, and ACVRL1 genes encoding proteins involved in transendothelial LDL transport, nor the MMP secretion by the EA.hy926cells. At the same time, adiponectin suppressed the TNF-stimulated IL-8 production and expression of the adhesion molecule gene ICAM1 in these cells. Thus, adiponectin reduces proinflammatory activation of EA.hy926 cells, which is not accompanied by changes in the transendothelial LDL transport. We speculate that anti-inflammatory action of adiponectin is the base for the influence of this adipokine on atherogenesis.

Role of adipokines in ovarian cancer epidemiology and prognosis.

Ovarian cancer is one of the most serious problems in modern oncological gynecology. The link between obesity (expressed in BMI, WHR, waist circumference, body weight) and ovarian cancer has been poorly studied. Obesity is defined as an excessive accumulation of bodily fat, exceeding its physiological needs and adaptability. Study results suggest a link between specific histological types of ovarian cancer with increased patients' BMI. Adipose tissue is hormonally active and secretes biologically active proteins called adipokines. Resistin and leptin may show proliferative and anti-apoptotic effects. There is currently increasing attention to adipokine levels in ovarian cancer research. The influence of adiponectin on the secretion of angiogenic factors by ovarian cancer cells has been shown. It has been proven that leptin is associated with a worse prognosis for patients treated with platinum compounds combined with paclitaxel/docetaxel. The relation has been observed between the level of resistin and the growth of neoplastic cells, their spread and the resistance to chemotherapy. The level of AdipoR1 may be independent prognostic factor in the case of epithelial ovarian cancer. The role of adipokine in the neoplasm development requires further investigation, in the view of fact that results of current research are still inconclusive. Considering increasing number of people suffering from obesity as well as the current analysis results, it is necessary to extend experimentation on the influence of obesity on the development and prognosis of ovarian cancer.

Influence of adiponectin and inflammatory cytokines in fatty degenerative atrophic muscle

Tendon rupture and nerve injury cause fatty infiltration of the skeletal muscle, and the adipokines secreted from the infiltrated adipocytes are known to contribute to chronic inflammation. Therefore, in this study, we evaluated the effects of the adipokines on chronic inflammation using a rat sciatic nerve-crushed injury model. In vitro and in vivo experiments showed that the expression of adiponectin was decreased (0.3-fold) and the expression of Il6 (~ 3.8-fold) and Tnf (~ 6.2-fold) was increased in the nerve-crushed group compared to that in the control group. It was also observed that the administration of an adiponectin receptor agonist decreased the levels of Il6 (0.38-fold) and Tnf (0.28-fold) and improved cellular viability (~ 1.9-fold) in vitro. Additionally, in the fatty infiltrated skeletal muscle, low adiponectin levels were found to be associated with chronic inflammation. Therefore, the local administration of adiponectin receptor agonists would prevent chronic inflammation.

The influence of adiponectin on carbohydrates, lipids, and lipoproteins metabolism: analysis of signaling mechanisms

Dysregulation of adipose tissue functions makes a significant contribution to the pathogenesis of metabolic syndrome, one of the most common diseases in recent years. Adipose tissue is an organ that secretes at least several dozen signaling molecules, adipokines. One of the most studied and at the same time mysterious adipokines is adiponectin. The latter is due to the lack of clear ideas about the biological role of this adipokine, the presence of its several molecular forms with different activity and several types of receptors to this adipokine localized in almost all cells of the body. The purpose of this review is to summarize and analyze the available information about the molecular mechanisms of the effect of adiponectin on metabolism of carbohydrates, lipids and lipoproteins. The literature search was conducted by the keywords "adiponectin" and "metabolic syndrome" in the Pubmed and Elibrary.ru databases for the period from 1995 to 2021.According to the results of the literature analysis, it is assumed that adiponectin is involved in energy metabolism as a «satiety» hormone that promotes the utilization and storage of energy-rich substrates, fatty acids and glucose, which prevents the development or mitigates the already developed insulin resistance. This reduces the amount of plasma triglycerides and increases the level of high-density lipoproteins in the plasma. Adiponectin affects metabolic processes by activating the AdipoR1-APPL1-LKB1-AMPK, AdipoR1-APPL1-p38, AdipoR2-PPARa cascades, and possibly by activating the ceramidase and phosphoinositide pathways and insulin signaling. In addition to the AdipoR1/2 receptors, the adhesion molecule T-cadherin may be involved in the transduction of the adiponectin signal in endothelial and muscle cells. The mechanisms of signal transduction from T-cadherin, as well as from AdipoR2, remain unclear. Studies on the mechanisms of the action of individual molecular forms of adiponectin are extremely rare. The analysis shows the complex nature of adiponectin signaling, many of the mechanisms of which remain undiscovered, and it is possible that the near future will bring us significant progress in this area.

The Influence of Adiponectin on Production of Apolipoproteins A-1 and E by Human Macrophages

The Influence of Adiponectin on Production of Apolipoproteins A-1 and E by Human Macrophages

Influence of Adiponectin and Leptin on the Kinetics of Human Pulp Cells

Adipocytokines, such as adiponectin and leptin, are expressed by adipocytes and are known as anti-metabolic syndrome factors. They are also thought to mediate calcification in mineralized tissue. We investigated the effects of adiponectin and leptin on the kinetics of human pulp cells using ELISA and western blot. After gaining informed consent, we obtained human pulp cells from three patients. After cultivation in Dulbecco’s Modified Eagle Medium (DMEM) without serum, cells from the 4th to 6th passages were incubated with various concentrations of adiponectin (1, 10, or 100 ng/mL) in DMEM or leptin (0.1, 1, or 10 ng/mL) in DMEM for 24 h. We confirmed that human pulp cells expressed adiponectin receptor 1 and leptin receptor. Although the proliferation index of these cells as measured by 5-bromo-2'-deoxyuridine (BrdU) incorporation increased in the presence of adiponectin in a dose-dependent manner, pulp cells stimulated with leptin showed no significant changes in BrdU incorporation. Alkaline phosphatase activity showed no significant changes after stimulation with either adipocytokine. Adiponectin induced expression of BMP-2 and osteopontin more strongly than did leptin. In particular, expression of BMP-2 increased in the presence of adiponectin in a dose-dependent manner. In contrast, the expression of dentin sialoprotein increased after stimulation with leptin. The expression of Runx2 was not observed from the cultured pulp cells stimulated with both molecules. These results indicate that adiponectin and leptin contribute to growth and differentiation of human pulp cells and may consequently affect the formation of secondary dentin or reparative dentin in the dentin-pulp complex.

Adiponectin links maternal metabolism to uterine contractility.

Adiponectin is secreted by adipose tissue and promotes insulin sensitivity. Low circulating adiponectin is associated with increased risk for preterm labor, but the influence of adiponectin on uterine myometrial physiology is unknown. We hypothesized that adiponectin receptors (AdipoRs) decrease myometrial contractility via AMPK to promote uterine quiescence in pregnancy. Using quantitative RT-PCR, we found that nonpregnant or pregnant human and mouse myometrium express AdipoR1 and AdipoR2 mRNAs. We confirmed AdipoR2 protein expression in human and mouse myometrium, with increased abundance in late mouse pregnancy. Both recombinant adiponectin and a pharmacologic AdipoR agonist, AdipoRon, potently inhibited uterine myometrial strip contractions in physiologic organ bath. The relaxation was independent of contractile stimulus (oxytocin, KCl, U46619). AdipoR agonists increased AMPK phosphorylation in pregnant mouse myometrium, and the direct AMPK activator A769662 also relaxed myometrial strips. However, the AMPK inhibitor dorsomorphin (compound C) blocked AMPK phosphorylation but did not abolish relaxation with either AdipoRon or A769662. In summary, adiponectin inhibits myometrial contractility consistent with the possibility that it is a previously unrecognized link between maternal metabolism and pregnancy maintenance. We also identify a separate role for AMPK regulating myometrial contractions that may influence labor onset.-Vyas, V., Guerra, D. D., Bok, R., Powell, T., Jansson, T., Hurt, K. J. Adiponectin links maternal metabolism to uterine contractility.

Suppressive Activity of Adiponectin on the Development of Allergic Rhinitis in Mice.

Adiponectin is accepted as playing pivotal roles in the development of allergic rhinitis (AR) through modulation of production of inflammatory mediators. Although it is also well known that neuropeptides, especially substance P (SP), function in the development and persistence of clinical conditions of AR, the influence of adiponectin on neuropeptide production is not well understood. The present study was designed to examine the influence of adiponectin on the production of SP both in vivo and in vitro. PC-12 cells (1×104 cells) were stimulated with 10.0 ng/ml nerve growth factor (NGF) for 2 h and then with 10.0 ng/ml capsaicin in the presence of different concentrations of adiponectin. After 72 h, culture supernatants were obtained, and SP levels were measured with enzyme-linked immunosorbent assay (ELISA). The influence of adiponectin on the total number of neurites developed per PC-12 cell and on the percentage of PC-12 cells with outgrowing neurites was also examined 24 and 72 h after the start of culture, respectively. In the second part of the study, BALB/c mice were sensitized intraperitoneally with 1.0 μg of ovalbumin and then challenged with intranasal ovalbumin. At 7 days following sensitization, these mice were treated with different doses of adiponectin intranasally in a volume of 5.0 μl. Nasal allergy-like symptoms, which were induced by bilateral application of 0.1 % OVA (5.0 μl), were assessed by counting sneezing and nasal rubbing behavior for 10 min immediately after nasal ovalbumin challenge. SP levels in nasal lavage fluid obtained 6 h after nasal ovalbumin challenge were examined by ELISA. Treatment of NGF-stimulated PC-12 cells with adiponectin suppressed SP production, which was induced by capsaicin stimulation. The minimum concentration of adiponectin that caused significant suppression was 7.5 ng/ml. On the other hand, adiponectin did not affect the total number of neurites and the percentage of PC-12 cells with outgrowing neurites, even at 1,000 ng/ml. Intranasal instillation of adiponectin into ovalbumin-sensitized mice at more than 10.0 ng/ml, but not 5.0 ng/ml, significantly inhibited the appearance of SP in nasal secretions, which was increased by intranasal challenge with ovalbumin. Adiponectin also suppressed the development of nasal allergic-like symptoms, sneezing and rubbing behavior, when ovalbumin-sensitized mice were treated intranasally with adiponectin at more than 10.0 ng/ml. The present results strongly suggested that adiponectin suppresses the production of SP and results in improvement of the clinical conditions of AR.

T allele at ADIPOQ rs1501299 G/T polymorphism is more susceptible to the influence of circulating adiponectin on arterial stiffness in nondiabetic men

BackgroundLow adiponectin levels are associated with increased insulin resistance (IR) and arterial stiffness in hypertensive patients, but higher adiponectin levels are also found in heart failure patients. This discrepancy has not been fully resolved, but it may be related to the adiponectin gene (ADIPOQ) which regulates adiponectin production. We aimed to investigate whether the relationship between adiponectin and arterial stiffness is associated with ADIPOQ rs1501299 G/T polymorphism in nondiabetic Korean men.MethodsIn nondiabetic men without disease (n = 301), anthropometric parameters, lipid profiles, IR, circulating adiponectin, and brachial-ankle pulse wave velocity (baPWV) were measured. rs1501299 G/T polymorphism was also analyzed.ResultsCirculating adiponectin levels were negatively correlated with baPWV and homeostatic model assessment-IR in the T allele carriers (n = 167), but this correlation was not observed in the GG subjects (n = 134). However, a positive correlation between baPWV and IR was observed in the GG subjects, but not in the T carriers. These patterns were maintained after the adjustment for confounding factors. A stepwise linear regression analysis revealed that circulating adiponectin and systolic blood pressure (BP) were the main influencing factors on baPWV levels in T carriers, but systolic BP, IR and age were the main contributors to increased baPWV levels in the GG subjects.ConclusionsThis study demonstrates that the relationship between circulating adiponectin and arterial stiffness is different according to ADIPOQ rs1501299 G/T polymorphism, and suggests that T allele is more susceptible to the influence of adiponectin on arterial stiffness than GG homozygotes. This information may prove to be useful for personal-based early prevention and management of atherosclerotic risk.

Combination treatment of adipose-derived stem cells and adiponectin attenuates pulmonary arterial hypertension in rats by inhibiting pulmonary arterial smooth muscle cell proliferation and regulating the AMPK/BMP/Smad pathway.

The present study aimed to assess the effects of therapy with adiponectin (APN) gene-modified adipose-derived stem cells (ADSCs) on pulmonary arterial hypertension (PAH) in rats and the underlying cellular and molecular mechanisms. ADSCs were successfully isolated from the rats and characterized. ADSCs were effectively infected with the green fluorescent protein (GFP)-empty (ADSCs-V) or the APN-GFP (ADSCs-APN) lentivirus and the APN expression was evaluated by ELISA. Sprague-Dawley rats were administered monocrotaline (MCT) to develop PAH. The rats were treated with MCT, ADSCs, ADSCs-V and ADSCs-APN. Then ADSCs-APN in the lung were investigated by confocal laser scanning microscopy and western blot analysis. Engrafted ADSCs in the lung were located around the vessels. Mean pulmonary arterial pressure (mPAP) and the right ventricular hypertrophy index (RVHI) in the ADSCs-APN-treated mice were significantly decreased as compared with the ADSCs and ADSCs-V treatments. Pulmonary vascular remodeling was assessed. Right ventricular (RV) function was evaluated by echocardiography. We found that pulmonary vascular remodeling and the parameters of RV function were extensively improved after ADSCs-APN treatment when compared with ADSCs and ADSCs-V treatment. Pulmonary artery smooth muscle cells (PASMCs) were isolated from the PAH rats. The antiproliferative effect of APN on PASMCs was assayed by Cell Counting Kit-8. The influence of APN and specific inhibitors on the levels of bone morphogenetic protein (BMP), adenosine monophosphate activated protein kinase (AMPK), and small mothers against decapentaplegia (Smad) pathways was detected by western blot analysis. We found that APN suppressed the proliferation of PASMCs isolated from the PAH rats by regulating the AMPK/BMP/Smad pathway. This effect was weakened by addition of the AMPK inhibitor (compound C) and BMP2 inhibitor (noggin). Therefore, combination treatment with ADSCs and APN effectively attenuated PAH in rats by inhibiting PASMC proliferation and regulating the AMPK/BMP/Smad pathway.

The influence of adiponectin and leptin levels on myocardial remodeling in patients with type 2 diabetes mellitus and gout

There is a growing number of patients with type 2 diabetes mellitus. As a component of the metabolic syndrome, type 2 diabetes is often associated with hyperuricemia and gout. These diseases worsen prognosis of concomitant cardiovascular disorders. To assess the relationship between adiponectin and leptin levels and echocardiographic parameters in patients with type 2 diabetes mellitus, gout, and a combination thereof. The study involved 30 men aged 41 to 70 years divided into 3 groups. The first group included 10 patients with type 2 diabetes, the second one 10 patients with gout, and the third group consisted of 10 men with a combination of type 2 diabetes and gout. In all patients the levels of glucose, immunoreactive insulin, HOMA-IR, adiponectin, and leptin were measured. All patients underwent echocardiography. The study revealed hyperglycemia in patients with type 2 diabetes and its combination with gout. Patients of all three groups had increased insulin resistance, insulin and leptin levels, decreased concentration of adiponectin. The thickness of interventricular sepum in systole and diastole, posterior wall of the left ventricle in diastole, myocarduial mass of the left ventricle, the size of the left atrium and the right ventricle increased in patients of all three groups. The study demonstrated compensatory hyperinsulinemia and insulin resistance, hypoadiponectinemia, hyperleptinemia, left ventricular hypertrophy, diastolic dysfunction, and intact ventricular contractility in patients with type 2 diabetes, gout, and their combination. Hypoadiponectinemia and hyperleptinemia play a role in remodeling of myocardium in these patients.

The influence of adiponectin on the transcriptomic profile of porcine luteal cells.

Reproductive functions are closely related to nutritional status. Recent studies suggest that adiponectin may be a hormonal link between them. Adiponectin is an adipocytokine, abundantly expressed in adipose tissues. It plays a dominant role in lipid and carbohydrate metabolism by stimulating fatty acid oxidation, decreasing plasma triglycerides, and increasing cells' sensitivity to insulin and has direct antiatherosclerotic effects. The hormone is also postulated to play a modulatory role in the regulation of the reproductive system. The aim of this study was to identify differentially expressed genes (DE-genes) in response to adiponectin treatment of porcine luteal ovarian cells. The global expression of genes in the porcine ovary was investigated using the Porcine (V2) Two-color gene expression microarray, 4 × 44 (Agilent, USA). Analysis of the microarray data showed that 701 genes were differentially expressed and 389 genes showed a fold change greater than 1.2 (p < 0.05). Among this number, 186 genes were up-regulated and 203 were down-regulated. The list of DE-genes was used for gene ontology analyses. The biological process list was generated from up-regulated and down-regulated DE-genes. We found that up-regulated products of DE-genes take part in 30 biological processes and down-regulated products in 9. Analysis of the interaction network among DE-genes showed that adiponectin interacts with genes involved in important processes in luteal cells. These results provide a basis for future work describing the detailed interactions and relationships explaining local regulation of adiponectin actions in the ovary of pigs.

Lower levels of plasma adiponectin and endothelial progenitor cells are associated with large artery atherosclerotic stroke

Background: Both adiponectin and endothelial progenitor cells (EPCs) have been proposed recently with anti-atherosclerosis effects. However, their impacts on vascular outcomes in patients with large artery atherosclerosis (LAA) are unclear. This study aimed to investigate the relationship between adiponectin, EPCs and stroke with a case-control design. Methods: The study cohort included 127 patients (61.3 ± 11.0 years; 73.2% men) with LAA stroke and 58 control subjects (60.9 ± 9.2 years; 70.7% men) referred for adiponectin and EPCs levels testing. We collected demographic, clinical, angiographical features, and laboratory data. Influence of adiponectin and EPCs levels on cerebral atherosclerosis and LAA stroke was analyzed with regression models. Results: The levels of adiponectin and EPCs in atherosclerotic stroke patients were significantly lower compared with matched controls (p < 0.05). Logistic regression analysis identified that reduced levels of adiponectin and EPCs were closely correlated with cerebral atherosclerosis and LAA stroke. The associations remained significant after adjustment for age, sex and other confounders. Additionally, partial correlation analysis revealed a significant positive association between adiponectin and three subpopulations of EPCs levels (CD34+CD133+CD309+cells: r = 0.510, p = 0.001; CD34+ CD133−CD309+cells: r = 0.262, p = 0.004; CD34−CD133+CD309+cells: r = 0.348, p < 0.001). Conclusions: Adiponectin is positively correlated with EPCs levels, and both of them are independently associated with LAA stroke.

Effects of the Serum Adiponectin to Tumor Necrosis Factor-α (TNF-α) Ratio on Carotid Intima-Media Thickness in Newly Diagnosed Type 2 Diabetic Patients

Objectives: Type 2 diabetes, a leading cause of cardiovascular disease, is well known for its association with accelerated atherosclerosis. Adiponectin and tumor necrosis factor alpha (TNF-α), which are produced and secreted in adipose tissue, have been suggested as predictors for cardiovascular disease. However, little is known about the influence of adiponectin and TNF-α ratio on the progression of carotid atherosclerosis in newly diagnosed type 2 diabetic patients. This study was conducted to evaluate the influence of serum adiponectin/TNF-α levels on the progression of carotid atherosclerosis. Methods: One hundred eleven newly diagnosed type 2 diabetes patients were enrolled. Anthropometric and biochemical data including serum adiponectin, TNF-α were measured for each participant. Also we measured carotid intima-media thickness (CIMT) at baseline and at 1 year follow-up (n=81). We finally examined the relationship among serum adiponectin over TNF-α levels (ADPN/TNF-α), baseline CIMT, and progression of CIMT at 1 year. Results: ADPN/TNF-α negatively correlated with baseline CIMT (r=-0.231, p=0.025). Moreover, progression of CIMT was significant at 1 year (0.011±0.138 mm). There was a negative correlation between ADPN/TNF-α and progression of CIMT at 1 year (r=-0.172, p=0.038). In multiple regression analysis, age and HbA1c were found to be independent risk factors for baseline CIMT. However, only HbA1c was an independent risk factor for the progression of CIMT. Conclusion: ADPN/TNF-α was negatively associated with baseline CIMT and the progression of CIMT at 1 year. Overall glycemic control is the most important factor in the progression of CIMT in patients with type 2 diabetes.

A1.42 Adiponectin: modulation of bone remodelling in rheumatoid arthritis

IntroductionAdiponectin is a strong effector molecule in the pathophysiology of RA, for example by contributing to the production of proinflammatory chemokines and matrix degrading enzymes synthesised by RA synovial fibroblasts....

The role of adiponectin in renal physiology and development of albuminuria

Adiponectin is secreted by the adipose tissue and is downregulated in states of obesity and insulin resistance. There is a growing body of evidence indicating that adiponectin has renoprotective effects and protects against the development of albuminuria in rodent experiments. Adiponectin crossing the glomerular filtration barrier possibly inhibits inflammation, fibrosis and oxidative stress in kidneys through activation of AMP-activated protein kinase. Moreover, microalbuminuria is a well established early sign of progressive cardiovascular and renal disease, even in subjects with preserved glomerular filtration rate. Studies investigating the relationship between serum adiponectin levels and urinary albumin excretion rate (UAE) have yielded conflicting data and the mechanisms underlying the interplay between adiponectin and albuminuria remain to be elucidated. This article constitutes a critical review attempting to clarify any remaining confusion about this matter. Furthermore, this article examines the clinical significance of adiponectin-albuminuria interplay, suggesting that adiponectin is possibly involved in the development of albuminuria that is associated with obesity, diabetes and cardiovascular disease and may mediate, at least in part, the actions of medical treatments that influence UAE, such as angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, thiazolidinediones, fenofibrate and diet. Further studies to investigate more thoroughly the renoprotective role of adiponectin in the human setting should be carefully planned, focusing on causality and the possible influence of adiponectin on the development of albuminuria in specific clinical settings.

Adiponectin: a manifold therapeutic target for metabolic syndrome, diabetes, and coronary disease?

Adiponectin is the most abundant peptide secreted by adipocytes, being a key component in the interrelationship between adiposity, insulin resistance and inflammation. Central obesity accompanied by insulin resistance is a key factor in the development of metabolic syndrome (MS) and future macrovascular complications. Moreover, the remarkable correlation between coronary artery disease (CAD) and alterations in glucose metabolism has raised the likelihood that atherosclerosis and type 2 diabetes mellitus (T2DM) may share a common biological background. We summarize here the current knowledge about the influence of adiponectin on insulin sensitivity and endothelial function, discussing its forthcoming prospects and potential role as a therapeutic target for MS, T2DM, and cardiovascular disease. Adiponectin is present in the circulation as a dimer, trimer or protein complex of high molecular weight hexamers, >400 kDa. AdipoR1 and AdipoR2 are its major receptors in vivo mediating the metabolic actions. Adiponectin stimulates phosphorylation and AMP (adenosin mono phosphate) kinase activation, exerting direct effects on vascular endothelium, diminishing the inflammatory response to mechanical injury and enhancing endothelium protection in cases of apolipoprotein E deficiency. Hypoadiponectinemia is consistently associated with obesity, MS, atherosclerosis, CAD, T2DM. Lifestyle correction helps to favorably modify plasma adiponectin levels. Low adiponectinemia in obese patients is raised via continued weight loss programs in both diabetic and nondiabetic individuals and is also accompanied by reductions in pro-inflammatory factors. Diet modifications, like intake of fish, omega-3 supplementation, adherence to a Mediterranean dietary pattern and coffee consumption also increase adiponectin levels. Antidiabetic and cardiovascular pharmacological agents, like glitazones, glimepiride, angiotensin converting enzyme inhibitors and angiotensin receptor blockers are also able to improve adiponectin concentration. Fibric acid derivatives, like bezafibrate and fenofibrate, have been reported to enhance adiponectin levels as well. T-cadherin, a membrane-associated adiponectin-binding protein lacking intracellular domain seems to be a main mediator of the antiatherogenic adiponectin actions. The finding of novel pharmacologic agents proficient to improve adiponectin plasma levels should be target of exhaustive research. Interesting future approaches could be the development of adiponectin-targeted drugs chemically designed to induce the activaton of its receptors and/or postreceptor signaling pathways, or the development of specific adiponectin agonists.

Influence of Adiponectin and Resistin Gene Polymorphisms on Quantitative Traits Related to Metabolic Syndrome Among Malay, Chinese, and Indian Men in Malaysia

Influence of Adiponectin and Resistin Gene Polymorphisms on Quantitative Traits Related to Metabolic Syndrome Among Malay, Chinese, and Indian Men in Malaysia

Oxidized low‐density lipoprotein and lipoprotein(a) levels in chronic kidney disease patients under hemodialysis: Influence of adiponectin and of a polymorphism in the apolipoprotein(a) gene

Chronic kidney disease (CKD) has been associated with an abnormal lipid profile. Our aim was to study the interplay between oxidized low-density lipoprotein (ox-LDL), adiponectin, and blood lipids and lipoproteins in Portuguese patients with CKD under hemodialysis (HD); the influence of the pentanucleotide repeat polymorphism in the apolipoprotein(a) (apo [a]) gene upon lipoprotein(a) (Lp[a]) levels in these patients. We studied 187 HD patients and 25 healthy individuals. ox-LDL and adiponectin were measured using enzyme-linked immunoassays. Apo(a) genotyping was performed by polymerase chain reaction, followed by electrophoresis in polyacrylamide gel. Compared with controls, patients presented with significantly higher levels of adiponectin, Lp(a), and ox-LDL/low-density lipoprotein cholesterol (LDLc) ratio; significantly lower levels of total cholesterol (TC), LDLc, apo A-I, apo B, ox-LDL, and TC/high-density lipoprotein cholesterol (HDLc) ratio were also observed. Similar changes were observed for patients with or without statin therapy, as compared with controls, except for Lp(a). Multiple linear regression analysis showed that body mass index, HDLc, time on HD, and triglycerides (TG) were independent determinants of adiponectin levels, and that apo B, TG and LDLc were independent determinants of ox-LDL concentration. Concerning the apo(a) genotype, the homozygous (TTTTA)8/8 repeats was the most prevalent (50.8%). A raised proportion of LDL particles that are oxidized was observed. Adiponectin almost doubled its values in patients and seems to be an important determinant in HDLc and TG levels, improving the lipid profile in these patients. Apo(a) alleles with a lower number of repetitions are more frequent in patients with higher Lp(a).

Adiponectin is a negative regulator of antigen‐activated T cells

Adiponectin (APN), a cytokine constitutively produced in fat tissue, has been shown to exert anti-inflammatory effects in various disease models. While the influence of APN on monocytic cells has been extensively studied in vitro, little is known about its role in T cells. In this study, we show that while <10% of human peripheral blood T cells express adiponectin receptors (AdipoRs) on their surface, most T cells store AdipoRs in intracellular compartments. AdipoRs colocalized with immune regulatory molecules CTLA-4 and TIRC7 within clathrin-coated vesicles. After stimulation, the expression of adiponectin receptor 1 (AdipoR1) and AdipoR2 was upregulated on the surface of antigen-specific T cells, as determined by tetramer or CD137 staining, and AdipoR1 and AdipoR2 coexpressed with CTLA-4. Addition of APN resulted in a significant diminution of antigen-specific T-cell expansion. Mechanistically, APN enhanced apoptosis and inhibited proliferation of antigen-specific T-cell lines. Further, APN directly inhibited cytokine production in response to antigen stimulation. In line with the in vitro data, APN-deficient (knockout, KO) mice had higher frequencies of CD137(+) T cells upon Coxsackie B virus infection. Altogether, our data suggest that APN is a novel negative T-cell regulator. In contrast to the CTLA-4 ligand B7 only expressed on APCs, APN is abundant in human plasma.