Role Of Adipokines Research Articles

The role of adipokines in the regulation of cardiovascular function

Adipose tissue is an endocrine organ secreting signal peptides adipokines. Adipokines play a significant role in the regulation of the immune, endocrine, nervous, excretory systems. Adipokine imbalance leads to chronic inflammation, metabolic and cardiovascular diseases. Obesity as the primary reason of the adipokine imbalance is the leading risk factor of hypertension, atherosclerosis and coronary artery disease. Thus, experimental and clinical studies of adipokine biology are essential for the development of the novel therapeutic approaches for the management of cardiometabolic diseases. This review focuses on the role of adiponectin, leptin, chemerin, omentin and visfatin in physiological and pathophysiological processes in the cardiovascular system.

Variants in ADIPOQ gene are linked to adiponectin levels and lung function in young males independent of obesity

BackgroundObesity is a major risk factor for many chronic diseases, including reduced lung function. The role of polymorphisms of the adiponectin gene, though linked with cardiometabolic consequences of obesity, has not been studied in relation to lung function.ObjectivesThe aim of this study is to examine polymorphisms in the ADIPOQ, ADIPOR1, and ADIPOR2 genes in relation to adiponectin serum levels, BMI, and adiposity in 18-year old Cypriot males, as well as determine whether BMI, adipokines levels and polymorphisms in adipokine related genes are associated with lung function levels.ResultsFrom the participants, 8% were classified as obese, 22% as overweight, and the remaining 71% as normal. We found that rs266729 and rs1501299 in ADIPOQ and rs10920531 in ADIPOR1 were significantly associated with serum adiponectin levels, after adjusting for ever smoking. In addition, there was an overall significant increase in FEV1% predicted with increasing BMI (β = 0.53, 95% CI: 0.27, 0.78) and in FVC % predicted (β = 1.02, 95% CI: 0.73, 1.30). There was also a decrease in FEV1/FVC with increasing BMI (β = -0.53, 95% CI: -0.71, -0.35). Finally, rs1501299 was associated with lung function measures.DiscussionFunctional variants in the ADIPOQ gene were linked with lung function in young males. Further studies should concentrate on the role of adipokines on lung function which may direct novel therapeutic approaches.

Does adiponectin play a role in the pathogenesis of chronic spontaneous urticaria?

IntroductionChronic spontaneous urticaria constitutes an interdisciplinary problem and its pathogenesis is still a subject of debate. Overweight and hyperlipidemia are supposed to be related to chronic spontaneous urticaria. Fatty tissue can be the source of adipokines.Aim of the studyTo assess the potential role of adiponectin in chronic spontaneous urticaria pathogenesis.Material and methodsThe study included 52 chronic spontaneous urticaria patients and 43 healthy controls. The patients were divided into two subgroups: patients with wheals only, and patients with urticaria and an accompanying angioedema. The adiponectin concentration was measured in all studied subjects.ResultsNo statistically significant difference in adiponectin level was determined between the studied groups and subgroups.ConclusionsWe are among the first to present the results of study to determine a possible role of adipokines in chronic spontaneous urticaria pathogenesis. We did not observe any difference in adiponectin level. In our opinion, it is necessary to conduct further analyses in this field.

Значение адипокинов и миокина при артериальной гипертензии у подростков с ожирением

Значение адипокинов и миокина при артериальной гипертензии у подростков с ожирением

Serum concentrations of selected adipokines in virus-related liver cirrhosis and hepatocellular carcinoma.

Aim of the studyHepatotropic viruses cause metabolic disturbances such as insulin resistance and hepatosteatosis. Moreover, metabolic factors, such as insulin resistance, obesity, and type 2 diabetes mellitus, increase the risk for hepatocellular carcinoma (HCC) in patients with virus-related liver cirrhosis. Cytokines secreted by the adipose tissue (adipokines) may be implicated in these metabolic disturbances, but there is little evidence regarding the role of adipokines in virus-related cirrhosis and HCC. Thus, we studied whether serum concentrations of selected adipokines were altered in patients with virus-related liver cirrhosis, including patients with HCC.Material and methodsWe included 43 patients with liver cirrhosis due to chronic hepatitis B or chronic hepatitis C. Of these patients, 36 had HCC and 7 did not have any malignant lesions. In addition to routine clinical and laboratory variables, we analyzed serum concentrations of betatrophin, insulin, vaspin, visfatin, and irisin.ResultsCompared with healthy controls, patients with HCC had significantly increased vaspin concentrations and significantly reduced irisin concentrations. Compared with controls, patients with virus-related cirrhosis, with or without HCC, had significantly increased concentrations of insulin and betatrophin. The serum visfatin concentration was non-significantly higher in patients with virus-related cirrhosis than in controls. None of the studied adipokines was a significant predictor of HCC. Serum concentrations of the studied adipokines were not related to cirrhosis severity or HCC stage.ConclusionsMetabolic parameters, including serum adipokine concentrations, are altered in patients with virus-related liver cirrhosis. Adipokines might be related to the HCC risk in these patients.

Роль адипокинов в формировании метаболических нарушений у больных шизофренией

Роль адипокинов в формировании метаболических нарушений у больных шизофренией

Role of TNFα and leptin signaling in colon cancer incidence and tumor growth under obese phenotype

Epidemiological studies over the last few decades have shown a strong influence of obesity on colon cancer risk and its progression. These studies have primarily focussed on the role of adipokines in driving cancer progression. We investigated the incidence of cancerous polyp formation and tumor progression in presence and absence of functional leptin along with exploring the role of tumor necrosis factor α (TNFα), under obese condition. By utilizing diet induced obese and genetically obese mice, carcinogen induced colon polyp formation was investigated. Experiments were performed using tumor tissues and cell lines to delineate the inter-relationship between leptin and TNFα. Data shown in this report indicates that in leptin knockdown obese mice, AOM/DSS induced polyps are smaller and lesser in numbers as compared to AOM/DSS induced polyps in diet induced obese mice. Further in vitro experiments suggest that abrogation of leptin associated pathways promote TNFα induced apoptosis. Mechanistically, we report that TNFα induces p53 independent cell death through up regulation of p53 upregulated modulator of apoptosis (PUMA). TNFα induced PUMA was inhibited upon pre- exposure of cells to leptin, prior to TNFα treatment. Collectively these results indicate that obesity due to leptin non-functionality facilitates TNFα induced colon cancer cell death.

The role of adipokines in the pathogenesis and course of selected respiratory diseases.

Adipose tissue is also a secretory organ producing active substances called adipokines. Some of them (apelin, resistin, adiponectin, leptin, chemerin, or visfatin) may play a role in the pathogenesis and course of respiratory diseases, e.g. COPD, asthma, pulmonary hypertension, or lung cancer. There are limited and conflicting data on the role of adipokines in asthma. It has been confirmed, however, that visfatin and leptin can be markers of inflammation in COPD. Elevated concentrations of leptin and resistin play a pro-inflammatory role in the development of cancer cachexia. The role of adipokines has also been demonstrated in pulmonary hypertension, and the apelinadiponectin axis disruption may exacerbate pulmonary hypertension.

Pediatric Obesity and the Immune System.

Obesity has reached pandemic proportion and represents a major risk for several comorbidities. In addition to metabolic and cardiovascular obesity-related diseases, recent evidence suggested that obesity might affect immune system function. Adipose tissue is considered an endocrine organ that actively secretes cytokines also referred to as “adipokines.” Adipokines play an important role in the control of human metabolism. The dysfunctional adipose tissue in obese individuals is characterized by an altered cytokine secretion pattern that promotes chronic low-grade inflammation. Epidemiological evidence highlights the association between obesity and allergic and immune-mediated diseases, such as asthma, allergic rhinitis, rheumatic arthritis, and psoriasis. Less is known about underlying pathogenic mechanisms. However, several recent in vivo and in vitro studies have reported that adipokines are involved in inflammatory and autoimmune disorders by influencing both innate and acquired immune responses. In addition, obesity has been associated with reduced immune surveillance and increased risk of cancer. This paper reviews the evidence regarding the role of adipokines in immune system regulation, with particular emphasis on autoimmune, allergic, and inflammatory disorders. Understanding how obesity affects immune system functions may enable researchers to find new potential therapeutic targets in the management of allergic and autoimmune diseases.

Adipokines, cortisol and cytokine alterations in recent onset anorexia nervosa. A case–control study

IntroductionPsychological and neuroendocrine alterations are typical characteristics in anorexia nervosa patients. The role of adipokines and cytokines as mediators of body systems’ adaptations to the patients’ abnormal eating behavior is not well understood. The duration of disease seems to be a determinant of nutritional status and associated hormone changes. We aimed to assess whether alterations in adipokines, cytokines and cortisol do already exist in patients with a recent disease onset by means of a case–control study. MethodsForty-one adolescent female patients on their first-episode and diagnosed with anorexia nervosa, were matched by age and socioeconomic status (SES) (1:1) with healthy girls. Leptin, soluble leptin receptor (sOB-R), adiponectin, cortisol, and the cytokines IL-1β, IL-2, IL-6 and TNF-α were examined. ResultsThe results showed reduced leptin and increased sOB-R and cortisol levels in AN patients. Adiponectin was also increased but opposite to the previous biomarkers did not correlate with BMI Z-score. Serum TNF-α and IL-2 showed significantly lower and higher values, respectively, in the AN patients than in the controls. Cortisol showed the strongest correlation with sOB-R (r=0.436; P=0.005). ConclusionsOur study confirms previous findings on adipokine and cortisol alterations in AN patients, while overall cytokine results did not show a clear disruption in AN patients with short disease duration. The results highlight the need to disentangle the role of the sOB-R in the interactions between leptin and cortisol secretion.

The Role of Adipokines in the Establishment and Progression of Head and Neck Neoplasms.

Adipokines constitute a family of protein factors secreted by white adipose tissue (WAT), that regulate the functions of WAT and other sites. Leptin, adiponectin and resistin, are the main adipokines present in serum and saliva, targeting several tissues and organs, including vessels, muscles, liver and pancreas. Besides body mass regulation, adipokines affect glucose homeostasis, inflammation, angiogenesis, cell proliferation and apoptosis, and other crucial cell procedures. Their involvement in tumor formation and growth is well established and deregulation of adipokine and adipokine receptors' expression is observed in several malignancies including those located in the head and neck region. Intracellular effects of adipokines are mediated by a plethora of receptors that activate several signaling cascades including Janus kinase/ Signal transducer and activator of transcription (JAK/ STAT pathway), Phospatidylinositol kinase (PI3/ Akt/ mTOR) and Peroxisome proliferator-activated receptor (PPAR). The present review summarizes the current knowledge on the role of adipokines family members in carcinogenesis of the head and neck region. The diagnostic and prognostic significance of adipokines and their potential role as serum and saliva biomarkers are also discussed.

Adiponectin, blood pressure and hypertension - a narrative review

Adipokines, cytokines derived from adipose tissue, not only herald and confirm fat tissue as the largest endocrine organ but are also associated with a number of pathological states including obesity, insulin resistance and diabetes. There is a growing body of research on the role of adipokines in blood pressure regulation and development of hypertension. One of these adipokines, adiponectin, is especially interesting, given that it has numerous beneficial effects which include increasing insulin sensitivity and antiatherogenic and anti-inflammatory effects. In recent years, there has been a number of studies examining its possibly protective role in hypertension. In this narrative review we summarize the evidence on the association of adiponectin and polymorphism of the gene which encodes it with blood pressure levels and risk of hypertension, which might provide ideas for future research of adiponectin as a biomarker and potential therapeutic target in this condition.

Role of adipokines in obstructive airway disease and diabetes mellitus

This review summarizes the state of the current literature relating to the associations of lung disease and adipokines (proteins produced by adipose tissue) in humans. The mechanistic basis for these associations in humans is not established, although a possible role for adipokines has been invoked. Leptin, a pro-inflammatory adipokine, and adiponectin, an anti-inflammatory adipokine, are causally associated with asthma in mice. Although human studies are currently inconclusive, high-serum leptin and low-serum adiponectin concentrations predict asthma, independent of obesity, in select population groups, such as premenopausal women in the United States. In contradistinction, low-serum leptin and high-serum adiponectin concentrations are associated with stable COPD, although these associations are likely confounded by fat mass. Interestingly, leptin may promote systemic and airway inflammation in stable COPD patients. On the other hand, COPD may upregulate systemic and lung adiponectin expression. The precise mechanism and significance of the associations between these adipokines and lung disease at the current stage are confusing and frankly paradoxical in places. It is now known that adipose tissue is not an inert organ simply for energy storage, but regulates systemic inflammation via a variety of secreted proteins (called adipokines). While the associations of obesity and adipokines with cardiovascular, endocrine, and rheumatological diseases are well described, the respiratory effects of obesity and adipokines are less well known. This review will focus on the effect of obesity and adipokines on asthma and chronic obstructive pulmonary disease (COPD) in humans. This area of research needs additional study that may open up novel therapeutic strategies for these lung diseases.

P4416Influence of rosuvastatin on the secretion of leptin and its receptor by adipocytes isolated from different adipose depots in patients with ischemic heart disease

Abstract Obesity is still a major health, social and economic problem throughout the world. Recently, it is important to study the role of adipokines of adipose tissue of various localization in the development of cardiovascular diseases, as well as methods for their pharmacological correction. Purpose The study was to evaluate the effect of rosuvastatin on the secretion of leptin and its receptor by adipocytes of different localization, as well as on the expression of their genes in patients with ischemic heart disease. Methods 29 patients with coronary heart disease which will be held coronary bypass surgery. Adipocytes were isolated from the samples of SAT, EAT and PVAT obtained during coronary artery bypass grafting, which were cultured for 24 hours with rosuvastatin 1 μmol/l and 5 μmol/l. A day later, the concentration of leptin and the leptin receptor in cell culture was determined. All study was carried out in compliance with the Helsinki Declaration, and its protocol was approved by the Ethical Committee of Research Institute. Statistical analysis was performed using Statistica 10.0. All patients gave written informed consent to participate in the study. Results 1 μmol/l of rosuvastatin increased the level of leptin 1.6 and 2.9 times higher in adipocytes SAT compared with EAT and PVAT, respectively, and 1.8 times higher in EAT than in PVAT, which is consistent with the results of expression leptin gene. The concentration of rosuvastatin 5 μmol/l had an effect only on adipocytes SAT, increasing the level of leptin 1.6 and 2.2 times in comparison with adipocytes EAT and PVAT. Rosuvastatin had no significant effect on leptin receptor soluble levels. The free leptin index was higher in adipocytes SAT in the presence of 1 μmol/l of rosuvastatin 1.6 and 2.8 times in comparison with adipocytes of EAT and PVAT. Conclusion The concentration of rosuvastatin 1 μmol/l had a more pronounced effect on adipocytes compared to a concentration of 5 μmol/l and increased the level of leptin and its expression in cell culture. At the same time, a high content of leptin under conditions of low expression of a soluble receptor to leptin in the presence of rosuvastatin 1 μmol/l can lead to leptin resistance, more pronounced in SAT adipocytes.

The Role of Adipokines as Circulating Biomarkers in Critical Illness and Sepsis.

Sepsis represents a major global health burden. Early diagnosis of sepsis as well as guiding early therapeutic decisions in septic patients still represent major clinical challenges. In this context, a whole plethora of different clinical and serum-based markers have been tested regarding their potential for early detection of sepsis and their ability to stratify patients according to their probability to survive critical illness and sepsis. Adipokines represent a fast-growing class of proteins that have gained an increasing interest with respect to their potential to modulate immune responses in inflammatory and infectious diseases. We review current knowledge on the role of different adipokines in diagnostic work-up and risk stratification of sepsis as well as critical illness. We discuss recent data from animal models as well as from clinical studies and finally highlight the limitations of these analyses that currently prevent the use of adipokines as biomarkers in daily practice.

Role of adipokine zinc-α2-glycoprotein in coronary heart disease.

Zinc-α2-glycoprotein (AZGP1) is a newly identified adipokine that is associated with lipid metabolism and vascular fibrosis. Although adipokines contribute to lipid dysfunction and its related diseases, including stroke and coronary heart disease (CHD), the role of AZGP1 remains unclear. In this study, the role of AZGP1 in atherosclerosis and CHD was investigated. Serum AZGP1 levels from control (n = 84) and CHD (n = 91) patients were examined by ELISA and its relationship with various clinical parameters was analyzed. Immunohistochemistry and immunofluorescence were used to detect the expression of AZGP1 and its receptor in coronary atherosclerotic arteries. THP-1 and human embryonic kidney 293 cells were used to verify its anti-inflammatory role in atherosclerosis. Serum AZGP1 levels in CHD patients were lower than controls (P < 0.01) and independently associated with CHD prevalence (P = 0.021). AZGP1 levels also inversely correlated with the Gensini score. Immunohistochemistry and immunofluorescence showed that AZGP1 and its receptor β3-adrenoceptor (β3-AR) colocalized in lipid-rich areas of atherosclerotic plaques, particularly around macrophages. In vitro, AZGP1 had no effect on foam cell formation but showed anti-inflammatory effects through its regulation of JNK/AP-1 signaling. In summary, AZGP1 is an anti-inflammatory agent that can be targeted for CHD treatment.

The role of adipokines in the improvement of diabetic and cardiovascular risk factors within a 52-week weight-loss programme for obesity

BackgroundObesity is an independent risk factor for cardiovascular disease and diabetes weight reduction not only reduces the risk for these diseases but leads to an alteration of the circulating adipokine levels. The aim of our study was to evaluate the effect of weight loss and lifestyle changes implemented in the form of the interdisciplinary weight management programme Optifast52® on cardiovascular and diabetic risk factors and on key adipokines. Methods72 morbidly obese patients were included in the programme, which consisted of a very low-calorie diet followed by incremental food introduction and dietary stabilisation, accompanied by medical surveillance, physical activity, dietary counselling and psychological support. At baseline, and after 14, 26 and 49 weeks, risk factor profiles and adipokine levels were evaluated. Results43 patients completed the programme with an average weight reduction of about 20%. Significant improvement was observed in the lipid and diabetic laboratory panels of all patients. In addition, adiponectin levels increased significantly (7.79 vs. 12.38μg/ml, p<0.001), while leptin levels decreased (7.29 vs 3.09ng/ml, p<0.001) during the course of the programme. ConclusionIn this study, Optifast52®, a multidisciplinary programme focusing on diet and lifestyle changes, was found not only to affect a decrease in parameters associated with diabetes and cardiovascular disease, but also to ameliorate in part the obesity-related imbalance of pro- and anti-inflammatory adipokines.

The role of adipokines in developmental programming: evidence from animal models

Alterations in the environment during critical periods of development, including altered maternal nutrition, can increase the risk for the development of a range of metabolic, cardiovascular and reproductive disorders in offspring in adult life. Following the original epidemiological observations of David Barker that linked perturbed fetal growth to adult disease, a wide range of experimental animal models have provided empirical support for the developmental programming hypothesis. Although the mechanisms remain poorly defined, adipose tissue has been highlighted as playing a key role in the development of many disorders that manifest in later life. In particular, adipokines, including leptin and adiponectin, primarily secreted by adipose tissue, have now been shown to be important mediators of processes underpinning several phenotypic features associated with developmental programming including obesity, insulin sensitivity and reproductive disorders. Moreover, manipulation of adipokines in early life has provided for potential strategies to ameliorate or reverse the adverse sequalae that are associated with aberrant programming and provided insight into some of the mechanisms involved in the development of chronic disease across the lifecourse.

Association of Adipokines and Insulin, Which Have a Role in Obesity, with Colorectal Cancer.

Obesity-related diseases are an important part of public health; and obesity is related with colorectal cancer. Adipocyte hypertrophy and visceral adipose tissue accumulation can cause adipocitis-related diseases and pathogenic adipocyte formation. Adipose tissue has a very important and active role in immune response formation. Cytokines/adipokines, which are secreted from adipose tissue, have an active role in communication between adipocytes and macrophages. Thus, visceral adipocyte is related with low-grade chronic systemic inflammation. Adipocytes have an important role in colorectal cancer pathogenesis because of proinflammatory cytokines, growth factors, and hormones secretion. Most highlighted cytokines are adiponectin, resistin, and ghrelin. Also, insulin resistance, glucose intolerance, increased plasma insulin levels, body mass index, insulin-like growth factor (IGF-1), glucose, and serum free fatty acids levels are considered to be related with colorectal cancer pathogenesis. Thus, in this review, we focus on the role of adipokines and insulin in colorectal cancer.

Role of Adipokines in the Association between Thyroid Hormone and Components of the Metabolic Syndrome.

Metabolic syndrome (MS) increases cardiovascular risk. The role of thyroid hormone on components of MS is unclear. We analyzed a sample of 4733 euthyroid subjects from SardiNIA study. In female thyrotropin (TSH) was significantly and positively associated with triglycerides (Standardized regression coefficients (β) = 0.081, p < 0.001). Free thyroxine (FT4) was positively associated with HDL (β = 0.056, p < 0.01), systolic blood pressure (SBP) (β = 0.059, p < 0.001), diastolic blood pressure (DBP) (β = 0.044, p < 0.01), and fasting glucose (β = 0.046, p < 0.01). Conversely, FT4 showed a negative association with waist circumference (β = −0.052, p < 0.001). In TSH was positively associated with triglycerides (β = 0.111, p < 0.001) and FT4 showed a positive association with DBP (β = 0.51, p < 0.01). The addition of leptin and adiponectin to the regression models did not substantially change the impact of thyroid hormones on components of MS. Our data suggest that, even within the euthyroid range, excess of truncal adipose tissue is associated with variations in FT4. Leptin and adiponectin exert an additive effect rather than a causal effect. Additional studies should be performed to determine the clinical significance of this finding.