Role Of Adipokines Research Articles

Adipokines and Autoimmunity in Inflammatory Arthritis.

Adipokines are adipose tissue-derived factors not only playing an important role in metabolism but also influencing other central processes of the body, such as inflammation. In autoimmune diseases, adipokines are involved in inflammatory pathways affecting different cell types. Many rheumatic diseases belong to the group of autoimmune diseases, for example rheumatoid arthritis (RA) and psoriatic arthritis. Due to the autoimmune responses, a chronic inflammatory milieu develops, which affects the whole body, including adipose tissue. Metabolic alterations such as obesity influence inflammatory responses in autoimmune diseases. Adipokines are bioactive mediators mainly produced by adipose tissue. Due to alterations of systemic adipokine levels, their role as biomarkers with diagnostic potential has been suggested in the context of rheumatic diseases. In the affected joints of RA patients, different synoviocytes but also osteoclasts, osteoblasts, and chondrocytes produce several adipokines, contributing to the unique inflammatory microenvironment. Adipokines have been shown to be potent modulatory effectors on different cell types of the immune system but also local cells in synovial tissue, cartilage, and bone. This review highlights the most recent findings on the role of adipokines in the pathophysiology of inflammatory arthritis with a distinct focus on RA in the quickly developing research field.

Inflammatory bowel disease and obesity: current state of issue

Inflammatory bowel disease (IBD) has been always associated by clinicians with impaired absorption of nutrients, chronic blood loss from mucosal defects, asthenic syndrome and weight deficit. In recent decades the incidence of IBD has significantly increased, especially in developed countries, and this is believed to be partly due to diet and lifestyle global changes. The prevalence of obesity has increased in parallel with the growth of IBD. In the course of epidemiological and clinical studies was found that obesity affects the course of the disease and the response to therapy in patients with IBD. There is an increasing evidence of the active role of adipokines in pro – and anti-inflammatory processes in both obesity and autoimmune disease in the gastrointestinal tract. Despite the fact that the data found on the subject of coherence between IBD and obesity was contradictory, most studies confirm the correlation between obesity and high risks of surgery on the intestine, deterioration of drug absorption, and the development of perianal complications in patients with IBD. The clinical significance of this problem in the context of a steady increase of the incidences of obesity and IBD in Russia and the world as a whole, as well as research data, indicate in favor of the mutual burden of these diseases. The present article demonstrates results of the сore researches conducted on the subject and identifies current, unresolved issues, which demonstrate necessity of further experimental and clinical studies.

Possible Impact of Early-Life Exposure to Perfluoroalkyl Substances on Later Childhood Adipokine Concentrations in Serum

Background: Early-life exposure to perfluoroalkyl substances (PFASs) has been linked to metabolic health changes during later childhood, and a role of adipokines is suspected. Aims: We examined the relative impact of PFAS exposure prenatally and during infancy on childhood adipokine concentrations in serum. Subjects: All children belonged to a prospective birth cohort born in the Faroe Islands in 2007-2009 and followed up through to age 9 years. Study design: Adipokine concentrations in serum were measured at birth and age 9 years. Developmental PFAS exposure was determined from serum concentrations of the five major PFASs at birth and 18 months. Infancy PFAS exposures were estimated by structural equations. Outcome measures: Adipokines measured in serum included adiponectin, leptin, leptin receptor, and resistin. The adjusted regression coefficients for the estimated infancy-age PFAS exposures were compared with those obtained for measured PFAS concentrations at birth and age 18 months, with consideration of potential effect modification by sex. Results: Negative associations were found for resistin at age 9 years in regard to infancy PFAS exposures, and weak, positive associations for infancy exposures were observed for adiponectin. These associations tended to be stronger than prenatal exposures. Sex-dependence of the associations were not observed. Conclusions: Lowered serum-resistin concentrations at age 9 years were most strongly associated with early postnatal PFAS exposures. These findings suggest that infancy may represent a vulnerable time window for PFAS-associated metabolic programming.

The Role of Apelin and Apelin Receptor Expression in Migration and Invasiveness of Colon Cancer Cells.

Colon cancer is the second deadliest malignancy for human. Its correlation with obesity has led to an increasing number of studies focusing on the role of adipokines in colon cancer development. Apelin, which belongs to the family of adipokines, affects several pathological processes, including heart diseases, obesity and carcinogenesis. In this study, we examined the importance of apelin and apelin receptor (APJ) during motility regulation of colon cancer cells. Colon cancer cells with overexpression of apelin receptor, as well as cells with down-regulation of apelin were used in this study. Migration and invasion ability was tested using Transwell® filters. The proteolytic activity was analyzed with fluorescent-substrate degradation assay and gelatin zymography. We also used confocal microscopy to examine migratory protrusion formation and the localization of MT1-MMP. The levels of AKT and ERK kinases were evaluated using Western blotting assay. Overexpression of APJ receptor resulted in increased migration and invasion abilities through stimulation of migratory protrusion formation and proteolytic activity. These processes were mediated by PI3K/AKT and MAPK signaling pathways. Opposite effect was obtained when the level of apelin was down-regulated. The level of apelin and its receptor is strictly connected with regulation of migration and invasion of colon cancer cells. Therefore, apelinergic system seems to be a promising target for anti-cancer therapy.

Roles of Adipokines in Digestive Diseases: Markers of Inflammation, Metabolic Alteration and Disease Progression.

Adipose tissue is a highly dynamic endocrine tissue and constitutes a central node in the interorgan crosstalk network through adipokines, which cause pleiotropic effects, including the modulation of angiogenesis, metabolism, and inflammation. Specifically, digestive cancers grow anatomically near adipose tissue. During their interaction with cancer cells, adipocytes are reprogrammed into cancer-associated adipocytes and secrete adipokines to affect tumor cells. Moreover, the liver is the central metabolic hub. Adipose tissue and the liver cooperatively regulate whole-body energy homeostasis via adipokines. Obesity, the excessive accumulation of adipose tissue due to hyperplasia and hypertrophy, is currently considered a global epidemic and is related to low-grade systemic inflammation characterized by altered adipokine regulation. Obesity-related digestive diseases, including gastroesophageal reflux disease, Barrett’s esophagus, esophageal cancer, colon polyps and cancer, non-alcoholic fatty liver disease, viral hepatitis-related diseases, cholelithiasis, gallbladder cancer, cholangiocarcinoma, pancreatic cancer, and diabetes, might cause specific alterations in adipokine profiles. These patterns and associated bases potentially contribute to the identification of prognostic biomarkers and therapeutic approaches for the associated digestive diseases. This review highlights important findings about altered adipokine profiles relevant to digestive diseases, including hepatic, pancreatic, gastrointestinal, and biliary tract diseases, with a perspective on clinical implications and mechanistic explorations.

Circulating pro fibrotic protein promotes fibrosis in liver

Abstract Background/Introduction Non-alcoholic steatohepatitis (NASH), driven by the obesity epidemic, has become the most common form of liver disease. Inflamed visceral adipose tissue secretes pro-inflammatory adipokines that are causal for systemic metabolic disorders. Role of adipokines in NASH, especially those from brown adipose tissues (BATokine) remain unclear. Purpose To show the pathogenic role of BATokine in NASH. Methods To identify and characterize the pathological roles of pro-fibrotic BATokine, we generated a murine obese NASH model by imposing a high fat diet in C57BL6/NCr mice, and murine systemic or BAT specific knockout (KO) models. We also conducted functional in-vitro studies with differentiated brown adipocytes. Results Analyzing two sets of DNA micro array data with bioinformatics, we identified a secreted form pro-fibrotic protein (sPFP) expressed in dysfunctional brown adipose tissues (BAT) in mice. Testing our biobank samples, we found this protein increased in plasma of NASH patients. We generated a murine obese NASH model by imposing a high fat diet in C57BL6/NCr mice for 9–10 months since 4 weeks of age, and found that sPFP is produced predominantly by BAT. In this model, we also found that sPFP increased in plasma. We generated a murine systemic or BAT specific sPFP knockout (KO) models and found that liver fibrosis ameliorated in these models. We also suppressed circulating sPFP with a peptide vaccine targeting this molecule, and found that sPFP vaccination therapy inhibited liver fibrosis. Next, we generated sPFP gain of function (GOF) model by the administration of plasmid encoding sPFP into skeletal muscle. Liver fibrosis augmented in sPFP-GOF model, and these results suggested that sPFP has causal role for the progression of fibrotic response in liver. In vitro studies with differentiated brown adipocytes showed that metabolic stress increased c-Fos in nuclear, and this was causal for an increase in sPFP level. Conclusions Our results suggest that one of the BATokines, sPFP, contributes for the progression of fibrotic responses in obese-NASH model. Inhibition of sPFP may become a therapy for NASH or obesity related fibrotic disorders. Funding Acknowledgement Type of funding source: None

Gender-dependent regulation of FABP4 and leptin according to atrial fibrillation burden

Abstract Aims Adiposity plays a key role in the pathogenesis of atrial fibrillation (AF). Its associated proteins are differentially released between male and female. FABP4 and leptin are mediators in adipose tissue-inflammatory effects. Our aim was to study their gender differential behavior on mechanisms associated with AF progression. Methods and results Two independent cohorts were analyzed: A) patients referred for AF catheter ablation (n=217) and patients with suspected coronary artery disease referred for a CT scan (without previous history of AF) (n=105). Protein levels were determined by multiplex fluorometric immunoassay. Gene mRNA expression was analyzed by real time polymerase chain reaction. Correlation between biomarkers was explored with heatmaps and Kendall correlation coefficients. Logistic regression and random forest model determined the best predictors of AF recurrence after catheter ablation. Our results showed: 1) a distinctive profile according to gender, with an increment of FABP4 levels in women (20±14, 29±18 and 31±17 ng/mL; p=0.007) and a decrease of leptin levels in men (22±15, 13±16 and 13±11 ng/mL; p=0.001) among control, paroxysmal and persistent AF groups, respectively; 2) sex differences regarding inflammatory profile, oxidative stress and autonomic indirect markers in AF; 3) a prominent role of adipokines to discriminate AF recurrence after ablation. In persistent AF, FABP4 was the best predictor (LR coefficient 1.067, 95% CI 1–1.14, p=0.046). Conclusion The major finding of the present study is the sex differences of FABP4 and leptin according to AF burden. The relationship of these adipokines with oxidative stress, inflammatory and autonomic indirect markers might explain part of the mechanisms underlying the AF perpetuation. Adipokines regarding Gender & AF burden Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Institute of Health Carlos III

Role of adipokines in systemic sclerosis pathogenesis.

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease with manifestations in multiple organs, including the skin, lung, heart, joints, gastrointestinal tract, kidney, and liver. Its pathophysiology is characterized by inflammation, fibrosis, and vascular damage, with an increased expression of numerous cytokines, chemokines, and growth factors. However, besides these growth factors and cytokines, another group of molecules may be involved in the pathogenesis of SSc: the adipokines. Adipokines are proteins with metabolic and cytokine-like properties, which were originally found to be expressed by adipose tissue. However, their expression is not limited to this tissue, and they can also be found in other organs. Therefore, this review will describe the current knowledge regarding adipokines in the context of SSc and try to elucidate their potential role in the pathogenesis of SSc.

Effect of Long-Term Pilates Exercise Trainings on Serum Levels of Visfatin, Chemerin and Resistin in Overweight Inactive Women

Background: The role of adipokines has been recognized in metabolic settings and obesity-related disorders. Therefore, the purpose of this study was to investigate the effect of 12-weeks of Pilates training on serum levels of some adipokines in inactive women with overweight. Methods: Twenty four accessible healthy overweight women with average BMI of 27.2 ± 1.1 kg/m2 participated in this quasi-experimental study. They randomly divided into two groups: exercise group (n=12) and control group (n=12). Pilates exercise training was performed during 12-weeks (3 sessions per week, 60 min per session). During this period, the control group did not have any exercise activities. Blood samples were taken in two steps 48 hours before and 48 hours after the last session and after 12-14 hours of fasting to measure serum levels of visfatin, chemerin and resistin levels. The dependent t-test was used to examine the within-group changes and covariance analysis was used to examine the changes in between-group changes. Results: The results of this study showed that after 12-weeks of Pilates exercise training, visfatin (P= 0.012), chemerin (P=0.002) and resistin changes (P=0.005) in the training group had a significant decrease in post-test compared to the pre-test, as well as there was a significant decrease in serum visfatin levels (P = 0.035), chermerin (P = 0.018) and resistin (P=0.045) in the exercise group compared to the control group. Conclusion: Based on the results of this study, Pilates exercise training is a stimulus factor for adipokines levels changes in inactive women with overweight. It is probably one of the causes of physiological changes is the activity of adipokines levels.

Adipocyte-specific deletion of Tcf7l2 induces dysregulated lipid metabolism and impairs glucose tolerance in mice

Aims/hypothesisTranscription factor 7-like 2 (TCF7L2) is a downstream effector of the Wnt/β-catenin signalling pathway implicated in type 2 diabetes risk through genome-wide association studies. Although its expression is critical for adipocyte development, the potential roles of changes in adipose tissue TCF7L2 levels in diabetes risk are poorly defined. Here, we investigated whether forced changes in Tcf7l2 expression in adipocytes affect whole body glucose or lipid metabolism and crosstalk between disease-relevant tissues.MethodsTcf7l2 was selectively ablated in mature adipocytes in C57BL/6J mice using Cre recombinase under Adipoq promoter control to recombine Tcf7l2 alleles floxed at exon 1 (referred to as aTCF7L2 mice). aTCF7L2 mice were fed normal chow or a high-fat diet for 12 weeks. Glucose and insulin sensitivity, as well as beta cell function, were assessed in vivo and in vitro. Levels of circulating NEFA, selected hormones and adipokines were measured using standard assays.ResultsReduced TCF7L2 expression in adipocytes altered glucose tolerance and insulin secretion in male but not in female mice. Thus, on a normal chow diet, male heterozygote knockout mice (aTCF7L2het) exhibited impaired glucose tolerance at 16 weeks (p = 0.03) and increased fat mass (1.4 ± 0.1-fold, p = 0.007) but no changes in insulin secretion. In contrast, male homozygote knockout (aTCF7L2hom) mice displayed normal body weight but impaired oral glucose tolerance at 16 weeks (p = 0.0001). These changes were mechanistically associated with impaired in vitro glucose-stimulated insulin secretion (decreased 0.5 ± 0.1-fold vs control mice, p = 0.02) and decreased levels of the incretins glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (0.6 ± 0.1-fold and 0.4 ± 0.1-fold vs control mice, p = 0.04 and p < 0.0001, respectively). Circulating levels of plasma NEFA and fatty acid binding protein 4 were increased by 1.3 ± 0.1-fold and 1.8 ± 0.3-fold vs control mice (p = 0.03 and p = 0.05, respectively). Following exposure to a high-fat diet for 12 weeks, male aTCF7L2hom mice exhibited reduced in vivo glucose-stimulated insulin secretion (0.5 ± 0.1-fold vs control mice, p = 0.02).Conclusions/interpretationLoss of Tcf7l2 gene expression selectively in adipocytes leads to a sexually dimorphic phenotype, with impairments not only in adipocytes, but also in pancreatic islet and enteroendocrine cells in male mice only. Our findings suggest novel roles for adipokines and incretins in the effects of diabetes-associated variants in TCF7L2, and further illuminate the roles of TCF7L2 in glucose homeostasis and diabetes risk.Graphical abstract

Role of adipokines in the assessment of severity and predicting the clinical course of acute pancreatitis.

Acute pancreatitis (AP) is one of the most common diseases requiring hospitalization with increasing incidence. This pathology has variable severity and is associated with significant morbidity and mortality. Early diagnosis, including prognosis of clinical course of the disease is key in the initial clinical management. However, currently available prognostic markers have variable efficacy and the limited utility. Adipokines that are released from the peripancreatic adipose tissue during AP may represent the easy to use and practical AP prognostic markers. This review discusses the current state of knowledge concerning the clinical value of the adipokines in AP, such as adiponectin, ghrelin, interleukin 6, interleukin 8, interleukin 18, leptin, neutrophil gelatinase associated lipocalin, obestatin, resistin, visfatin. Among described adipokines, interleukin 6, neutrophil gelatinase associated lipocalin and resistin seem to be the most valuable as the diagnostic and prognostic markers in AP.

CLINICAL AND THERAPEUTIC VALUE OF ADIPOKINES IN PATIENTS WITH CHRONIC KIDNEY DISEASE

This review is devoted to the analysis of the role of adipokines in formation of pathological changes in renal function and structure. The patients with chronic kidney disease have a high risk of cardiovascular disease. Currently, the role of systemic hormonal and metabolic factors in the pathogenesis of the kidneys is growing. A promising area of pathogenetic prevention and treatment of kidney disease is an interdisciplinary approach, whereat the adipokine imbalance is of particular interest. Adipose tissue and its messengers, adipokines, are known to be highly associated with kidney disease. Adipocytes are metabolically active cells, producing the signaling lipids, metabolites and protein factors, i.e. adipokines. The interaction of adipose tissue with the kidney is called the adipose kidney axis, being important for the normal functioning of the body, as well as its response to an injury. It has a strong therapeutic potential in respect of the growing rates of chronic kidney disease. Adipocyte hypertrophy is often accompanied by the development of tissue fibrosis, hypoxia, and secretion of pro−inflammatory cytokines (such as tumor necrosis factor or interleukin, which triggers the cell inflammation). Dysfunction of adipose tissue contributes to the development of cardiovascular disease at the local and systemic levels. Thus, for the early diagnosis of chronic kidney disease into the diagnostic program, in addition to the generally accepted indices, the determination of adipokines: for example, serum leptin, adiponectin, omentin, visfatin, microalbuminuria, blood lipid spectrum, intrarenal and functional status of the kidneys with the assessment of functional renal reserve is recommended to be included. Early detection of the disease, new approaches to its diagnosis and treatment can help in reducing the risk of a high incidence and mortality from renal disease. Key words: chronic kidney disease, nephropathy, adipokines, leptin, resistin, adiponectin, visfatin, omentin.

Visfatin and resistin: role in health and disease

Adipose tissue is an endocrine organ secreting numerous neuroendocrine and peripheral peptides known as adipokines. The analysis of the essential scientific papers published from 2002 to the present has been made. Despite the fact that the role of adipokines remains controversial, their participation in metabolism, inflammation and the functioning of the endocrine system has been convincingly proven. Visfatin is an endocrine, autocrine, and paracrine peptide with many functions, including enhancing cell proliferation, nicotinamide biosynthesis, and a hypoglycemic effect. Resistin is a peptide hormone originally found in mice as a factor that induces insulin resistance. The article provides systematic information about publications concerning the study of the role of visfatin gene polymorphism. The molecular and endocrine mechanisms of visfatin and resistin and their role in the development of diabetes mellitus, insulin resistance, endothelial dysfunction, cardiovascular disease and atherosclerosis are presented. The role of these adipokines in the formation of perinatal complications in cases of impaired carbohydrate metabolism in pregnant women was evaluated according the analysis of published data. The review also demonstrates that hyperglycemia, obesity, excessive weight gain during gestation lead to impaired synthesis and function of the analyzed cytokines in adipose tissue, and to the development of fetal macrosomia. It is shown that visfatin and resistin can be considered as biological markers of pathological processes, and the further study will create the prerequisites for developing new preventive strategies and optimizing the treatment process.

The relationship between serum adipokines and glucose homeostasis in normal-weight and obese patients on hemodialysis: a preliminary study.

Insulin resistance (IR) is a prevalent disorder in advanced renal failure irrespective of diabetes. Adipokines might play a role in IR, which has not been well-documented in uremic conditions. This study investigated the relationship of Zinc-α2-glycoprotein (ZAG), adipose triglyceride lipase (ATGL), and adipolin with glucose-insulin homeostasis in normal weight (NW) and obese (OB) patients with hemodialysis. In this cross-sectional study, 59 patients (29 NW; 18.5 ≤ BMI < 25kg/m2, and 30 OB; BMI ≥ 30kg/m2) were studied. Anthropometries, circulating ZAG, adipolin, ATGL, free fatty acids (FFAs), fasting blood glucose (FBG), insulin, and homeostasis model assessmentof IR (HOMA)-IR were assessed. There were no significant differences in age, gender, hemodialysis duration, dialysis adequacy and diabetes between the two groups. ZAG (100.9 ± 37.1 vs. 107.5 ± 30.5ng/mL, P = 0.03) and adipolin (12.4 ± 1.6 vs. 13.2 ± 2.8ng/mL, P = 0.002) concentrations were significantly lower, and FFAs (228.1 ± 112.6 vs. 185 ± 119ng/mL, P = 0.014) were significantly higher in the OB than NW group. No significant differences were observed in ATGL, FBG, insulin and HOMA-IR between the two groups. Patients with lower IR had higher ZAG (112.9 ± 31.7 vs. 94.9 ± 34.5ng/mL; P = 0.046), lower FFAs (167.8 ± 98.4 vs. 249.9 ± 120.8ng/mL; P = 0.004), and marginally lower ATGL (9.1 ± 5.2 vs. 12.3 ± 9.6 mIU/mL; P = 0.079) concentrations than those with higher IR. ZAG was negatively (r = - 0.323, P = 0.018 and r = - 0.266, P = 0.054) and FFAs were positively (r = 0.321, P = 0.019 and r = 0.353, P = 0.009) correlated with insulin and HOMA-IR, respectively. ATGL was directly correlated with FFAs (r = 0.314, P = 0.018). Novel adipokines, ZAG and ATGL, might contribute to glucose-insulin homeostasis in hemodialysis. Understanding potential causative, diagnostic or therapeutic roles of adipokines in IR require further studies.

The Role of Adipokines and Bone Marrow Adipocytes in Breast Cancer Bone Metastasis.

The morbidity and mortality of breast cancer is mostly due to a distant metastasis, especially to the bone. Many factors may be responsible for bone metastasis in breast cancer, but interactions between tumor cells and other surrounding types of cells, and cytokines secreted by both, are expected to play the most important role. Bone marrow adipocyte (BMA) is one of the cell types comprising the bone, and adipokine is one of the cytokines secreted by both breast cancer cells and BMAs. These BMAs and adipokines are known to be responsible for cancer progression, and this review is focused on how BMAs and adipokines work in the process of breast cancer bone metastasis. Their potential as suppressive targets for bone metastasis is also explored in this review.

The role of adipokines in the modulation of lymphoid lineage cell development and activity: An overview.

Adipokines are predominantly known to play a vital role in the control of food intake, energy homeostasis and regulation of glucose and lipid metabolism. However, evidence supporting the concept of their extensive involvement in immune system defence mechanisms and inflammatory processes continues to grow. Some of the adipokines, that is, leptin and resistin, have been recognized to exhibit mainly pro-inflammatory properties, whereas others such as visfatin, chemerin, apelin and vaspin have been found to exert regulatory effects. In contrast, adiponectin or omentin are known for their anti-inflammatory activities. Hence, adipokines influence the activity of various cells engaged in innate immune response and inflammatory processes mainly by affecting adhesion molecule expression, chemotaxis, apoptosis and phagocytosis, as well as mediators production and release. However, much less is known about the role of adipokines in processes involving lymphoid lineage cells. This review summarizes the current knowledge regarding the importance of different adipokines in the lymphopoiesis, recirculation, differentiation and polarization of lymphoid lineage cells. It also provides insight into the influence of selected adipokines on the activity of those cells in tissues.

Thoracic Visceral Adipose Tissue Area and Pulmonary Hypertension in Lung Transplant Candidates. The Lung Transplant Body Composition Study.

Rationale: Obesity is associated with an increased risk of pulmonary hypertension (PH); however, regional adipose tissue deposition is heterogeneous with distinct cardiovascular phenotypes.Objectives: To determine the association of body mass index (BMI) and thoracic visceral and subcutaneous adipose tissue areas (VAT and SAT, respectively) with PH in patients with advanced lung disease referred for lung transplantation.Methods: We studied patients undergoing evaluation for lung transplantation at three centers from the Lung Transplant Body Composition Study. PH was defined as mean pulmonary artery pressure >20 mm Hg and pulmonary vascular resistance ≥3 Wood units. VAT and SAT were measured on chest computed tomography and normalized to height squared.Results: One hundred thirty-seven (34%) of 399 patients included in our study had PH. Doubling of thoracic VAT was associated with significantly lower pulmonary vascular resistance (β, -0.24; 95% confidence interval [95% CI], -0.46 to -0.02; P = 0.04), higher pulmonary arterial wedge pressure (β, 0.79; 95% CI, 0.32 to 1.26; P = 0.001), and decreased risk of PH (relative risk, 0.86; 95% CI, 0.74 to 0.99; P = 0.04) after multivariate adjustment. Vaspin levels were higher in patients without PH (median, 101.8 vs. 92.0 pg/ml; P < 0.001) but did not mediate the association between VAT and the risk of PH. SAT and BMI were not independently associated with risk of PH.Conclusions: Lower thoracic VAT was associated with a higher risk of PH in patients with advanced lung disease undergoing evaluation for lung transplantation. The role of adipokines in the pulmonary vascular disease remains to be evaluated.

The Role of Adipokines in the Development of Arterial Stiffness and Hypertension.

The study aimed to assess the role and the relationship of adipokines as well as parameters of arterial stiffness in newly diagnosed hypertension. Forty-nine newly diagnosed hypertensive cases (median age 47 ± 6 years) and 48 normotensive patients (median age 47 ± 6 years) were enrolled to this study. Patients underwent echocardiography, noninvasive assessment of hemodynamic parameters using SphygmoCor tonometer (Atcor Med). The levels of the adipokines-leptin, adiponectin, and resistin-were investigated. The augmentation pressure, augmentation index, and pulse wave velocity (PWV) were higher in patients with hypertension compared with controls (Ps < .05). Patients with hypertension had higher E/E' ratio, higher diameter of left atrium, and lower tricuspid annular plane systolic excursion compared with the control group (Ps < .05). Patients with hypertension had significant higher levels of leptin (ng/mL) and lower levels of adiponectin (μg/mL) compared with normotensive patients. The multivariate analysis showed that PWV (odds ratio [OR] 1.95, 95% CI, 1.2-2.9; P = .002) and leptin level (OR 1.01, 95% CI, 1.004-1.031; P = .01) were significantly associated with hypertension. Arterial stiffness as determined by PWV and leptin are associated with newly diagnosed hypertension. Elevated serum leptin level may influence the potential mechanism leading to sympathetic activation.

Research progress on the role of adipokines in intervertebral disc degeneration

To review the research progress of the role and mechanism of adipokines in intervertebral disc degeneration (IVDD) in recent years. The domestic and foreign literature related to adipokines in the process of IVDD was extensively reviewed. The types and functions of adipokines, the role and mechanism in the process of IVDD, and the application prospects of intervertebral disc biotherapy were reviewed. As a kind of bioactive substance secreted by adipose tissue, adipokine plays an important role in bone and joint diseases, metabolic diseases, and breast cancer. During IVDD, most adipokines can activate multiple signaling pathways by binding to autoreceptors, cause the proliferation and apoptosis of cells and proinflammatory and anti-inflammatory factors parasecretions in the intervertebral disc, and lead to imbalance of intradiscal metabolism and establishment of the initial inflammatory environment, and finally cause the IVDD. Adipokines, as a biologically active substance with metabolic and immunomodulatory functions, play important roles in the occurrence, development, and biological treatment of IVDD.

The role of selected adipokines in tumorigenesis and metabolic disorders in patients with adrenal tumors.

Recently, more and more attention has been directed to the role of adipose tissue and adipocytokines in the pathogenesis of metabolic and inflammatory disorders in humans. Excess fat tissue has also been associated with a higher risk of malignancies. Advances in the research on the role of adipokines in adrenal tumors may elucidate the relationship between various types of adipose tissue (visceral, subcutaneous, and periadrenal) and metabolic disorders observed in hormonally active adrenal tumors, as well as associations with adrenal cortex cancer. In patients with active or cured Cushing syndrome, increased leptin and resistin concentrations as well as release of pro-inflammatory cytokines can be associated with cardiovascular risk. Also, the renin-angiotensin-aldosterone system in patients with primary hyperaldosteronism may affect the metabolic activity of the adipose tissue. Elevated resistin concentrations in this group of patients are associated with morphological changes of the myocardium independently of the effects of the metabolic syndrome. Further, it has been suggested that hypoadiponectinemia comprises an additional factor in the pathogenesis of carbohydrate metabolism disorders and the risk of cardiovascular complications in pheochromocytoma patients. Understanding the mechanisms of action of adipokines may be important in developing prophylactic and therapeutic strategies in hormonally active and malignant tumors of the adrenal glands.