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Purpose: Hypertension is one of the major risk factors for renal failure and cardiovascular diseases, and is caused by various abnormalities including the contractility of blood vessels. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which mimic human type 2 diabetes, are frequently used to study obesity-induced insulin resistance (IR) and hypertension. Human omentin-1 is one of the recently identified adipocytokines. We previously demonstrated that human omentin-1 not only caused vasodilation in rat isolated blood vessels, but also prevented inflammatory responses, a possible mechanism relating IR, in human vascular endothelial cells. Taken together, we hypothesized that human omentin-1 may reduce obesity-induced IR and hypertension in OLETF rats. Methods: OLETF rats were intraperitoneally administered with human omentin-1 for 7 days. Results: Human omentin-1 had no influence on overweight, hyperglycemia, urinary glucose extraction, hyperinsulinemia, and systemic IR in OLETF rats. Human omentin-1 decreased systolic blood pressure in OLETF rats. The measurement of isometric contraction revealed that human omentin-1 had no influence on the agonist-induced contractile and relaxant responses in isolated thoracic aorta from OLETF rats. However, the relaxant response mediated by human insulin was converted into the contractile response in thoracic aorta from OLETF rats, which was prevented by human omentin-1. The Western blotting revealed that human omentin-1 improved the decrease in endothelial nitric oxide synthase activation in isolated thoracic aorta from OLETF rats. Conclusion: In summary, we for the first time revealed that human omentin-1 partly reduces vascular IR and thereby inhibits hypertension in OLETF rats. [ABSTRACT FROM AUTHOR]

Background: Periodontitis is a chronic inflammatory disease caused by bacterial infection in the periodontal support tissue. Visfatin, a hormone secreted mainly by adipocytes and macrophages, plays an important role in immune regulation and defense. Although studies have indicated that patients with periodontitis have significantly high serum and gingival crevicular fluid levels of visfatin, the relationship between this adipocytokine and periodontal disease remains unclear. Aim: The aim of this study was to systematically evaluate the association between visfatin levels and periodontitis. Methods: The PubMed, Web of Science, ScienceDirect, EBSCO, and Wiley Online Library databases were searched for potential studies, using "periodontitis" and "visfatin" as the keywords in the title and abstract search fields. Standardized mean difference (SMD) values with corresponding 95% confidence intervals (CIs) were determined from the results of this meta-analysis. Results: In total, 22 articles involving 456 patients with periodontitis and 394 healthy individuals (controls) were included in the meta-analysis. Visfatin levels were significantly higher in the patients with periodontitis than in the healthy individuals (SMD: 3.82, 95% CI [3.01-4.63]). Moreover, the visfatin levels were significantly lowered after periodontitis treatment (SMD: -2.29, 95% CI [-3.33 to -1.26]). Conclusion: This first-ever meta-analysis comparing visfatin levels between patients with periodontitis and healthy individuals suggests that this adipocytokine can be a diagnostic and therapeutic biomarker for periodontal disease. [ABSTRACT FROM AUTHOR]

Obesity is one of the major factors threatening human health. Excessive fat accumulation not only has detrimental effects on human metabolism and cardiovascular system, but also is highly correlated to the incidence and mortality of various tumors. Fatty acid binding protein-4 (FABP4) is a small molecule protein mainly expressed in adipocytes and macrophages, and is responsible for participating in fatty acid transport and lipid response. It has been found that FABP4 levels are not only associated with body fat content, but also aberrantly expressed in various obesity-associated tumor cells and tumor microenvironment, which is closely related to obesity-associated carcinogenesis, metastasis, recurrence and patient prognosis. Since FABP4 expression varies in different types of obesity-associated tumors, suggesting a complex role of FABP4 in tumorigenesis. Based on this, this article reviews different roles of FABP4 in multiple obesity-associated tumors.

Context: Breast cancer is the most common diagnosis established in women with malignant tumors. Aims: The purpose is to investigate the blood contents of adiponectin and leptin in women with breast cancer and obesity. Settings and Design: A total of 140 women aged 40–50 were examined. Materials and Methods: Group 1 included 70 women from classes 1 or 2 obesity. Group 2 included 70 women with stage 1 or 2 breast cancer and classes 1 or 2 obesity. The control group included 30 apparently healthy women, with mean age of 42.5 ± 2.5 years. Statistical Analysis Used: Statistical processing of the results obtained was performed using Statistica. Results: Groups 1 and 2 were statistically significantly different from each other across all parameters, except for leptin resistance. In group 2, the course of breast cancer with concomitant obesity is characterized by disrupted adipocytokine homeostasis, which manifests as a 1.94-fold decrease in the blood content of adiponectin (P < 0.05), a 4.14-fold increase in the blood content of leptin (P < 0.05), and an 8.00-fold increase in the leptin/adiponectin ratio (P < 0.05). Poorly differentiated breast tumors exhibit a more pronounced imbalance in the blood levels of adipocytokines. Thus, the serum content of leptin in women with poorly differentiated tumors (G3) was 1.79 times (P < 0.05) higher than in women with moderately differentiated tumors (G2). Conclusions: The course of breast cancer with concomitant obesity is characterized by disrupted adipocytokine homeostasis and decreased adiponectin concentration in the blood. [ABSTRACT FROM AUTHOR]

Obesity-associated perturbations in the normal secretion of adipocytokines from white adipocytes can drive the metastatic progression of cancer. However, the association between obesity-induced changes in secretory factors of white adipocytes and subsequent transactivation of the downstream effector proteins impacting metastasis in breast cancer cells remains unclear. Focal adhesion kinase, a cytoplasmic signal transducer, regulates the biological phenomenon of metastasis by activating downstream targets such as beta-catenin and MMP9. Thus, the possible role of phosphorylated FAK in potentiating cancer cell migration was investigated. To elucidate this potential relationship, MCF7 (ER+), MDA-MB-231 (Triple Negative) breast cancer cells, and MCF-10A non-tumorigenic breast cells were exposed to in vitro murine adipocyte-conditioned medium derived from 3T3-L1 MBX cells differentiated to obesity with fatty acid supplementation. Our results show that the conditioned medium derived from these obese adipocytes enhanced motility and invasiveness of breast cancer cells. Importantly, no such changes were observed in the non-tumorigenic breast cells. Our results also show that increased FAK autophosphorylation was followed by increased expression of beta-catenin and MMP9 in the breast cancer cells when exposed to obese adipocyte-conditioned medium, but not in the MCF10A cells. These results indicate that adipocyte-derived secretory factors induced FAK activation through phosphorylation. This in turn increased breast cancer cell migration and invasion by activating its downstream effector proteins beta-catenin and MMP9. [ABSTRACT FROM AUTHOR]

Nicotinamide phosphoribosyltransferase (NAMPT) plays a central role in mammalian cell metabolism by contributing to nicotinamide adenine dinucleotide biosynthesis. However, NAMPT activity is not limited to the intracellular compartment, as once secreted, the protein accomplishes diverse functions in the extracellular space. Extracellular NAMPT (eNAMPT, also called visfatin or pre-B-cell colony enhancing factor) has been shown to possess adipocytokine, pro-inflammatory, and pro-angiogenic activities. Numerous studies have reported the association between elevated levels of circulating eNAMPT and various inflammatory and metabolic disorders such as obesity, diabetes, atherosclerosis, arthritis, inflammatory bowel disease, lung injury and cancer. In this review, we summarize the current state of knowledge on eNAMPT biology, proposed roles in disease pathogenesis, and its potential as a disease biomarker. We also briefly discuss the emerging therapeutic approaches for eNAMPT inhibition. [ABSTRACT FROM AUTHOR]

Nicotinamide phosphoribosyltransferase (NAMPT) plays a central role in mammalian cell metabolism by contributing to nicotinamide adenine dinucleotide biosynthesis. However, NAMPT activity is not limited to the intracellular compartment, as once secreted, the protein accomplishes diverse functions in the extracellular space. Extracellular NAMPT (eNAMPT, also called visfatin or pre-B-cell colony enhancing factor) has been shown to possess adipocytokine, pro-inflammatory, and pro-angiogenic activities. Numerous studies have reported the association between elevated levels of circulating eNAMPT and various inflammatory and metabolic disorders such as obesity, diabetes, atherosclerosis, arthritis, inflammatory bowel disease, lung injury and cancer. In this review, we summarize the current state of knowledge on eNAMPT biology, proposed roles in disease pathogenesis, and its potential as a disease biomarker. We also briefly discuss the emerging therapeutic approaches for eNAMPT inhibition.

The increasing prevalence of obesity has prompted intensive research into understanding its role in pathogenesis and designing appropriate treatments. To determine the signals generated from the interaction of fat cells with a target organ, a reliable white adipocyte model in vitro is needed. Differentiated fibroblasts are the most extensively studied using in vitro cell models of white adipocytes. However, it can be argued that differentiated fibroblasts minimally recapitulate the consequences of obesity. Here, we describe 3T3-L1 MBX cells as a culture model for studying obese adipocytes and their effects. Differentiation of 3T3-L1 MBX cells was at first optimized and then maintained in the presence of fatty acids cocktail combination to induce the obese condition. Lipid accumulation and adipokine secretion profiles were analyzed. Results showed that fatty acid-maintained, differentiated 3T3-L1 MBX cells had significantly greater accumulation of lipids and significant changes in the adipokine secretions in comparison to differentiated 3T3-L1 MBX cells maintained in medium without fatty acids. To elucidate the molecular changes associated with adipogenesis and lipid accumulation profile of 3T3-L1 MBX cells, we have also explored the expression of some of the regulatory proteins related to the development and maintenance of adipocytes from the preadipocyte lineage. [ABSTRACT FROM AUTHOR]

Diabetes Mellitus (DM), a metabolic disease characterized by the increased blood glucose level, insulin deficiency or ineffectiveness, may cause structural and functional disorders in the brain. l -Theanine (LTN) has the relaxing, psychoactive, antidepressant, anti-inflammatory and antinecrotic properties, and regulates the functions of hippocampus (HP) in brain. In the present study, the aim was to identify the effects LTN on the levels of BDNF, insulin and adipocytokines (TNF-α, leptin, adiponectin and resistin) in both HP and serum of diabetic rats. 32 male Wistar rats were divided into four groups (n = 8/group): Control, LTN, DM and DM + LTN. Diabetes was induced by by nicotinamide/streptozotocin. 200 mg/kg/day LTN treatment was applied for 28 days. The serum and hippocampal levels of the parameters were determined by using commercial ELISA kits. Additionally, HP tissues examined histopathologically. LTN treatment significantly decreased leptin and adiponectin levels in HP tissues in diabetic rats (p < 0.05). Although it decreased the insulin level in both serum and HP, this was not statistically significant. No significant effect on other parameters was observed (p > 0.05). In histopathological analysis, although the damage was reduced by LTN in all sections of HP, this change was significant mainly in CA3 region (p < 0.05). It was concluded that LTN has the ability to reduce hippocampal degeneration and modulates adipocytokines in diabetic rats. [Display omitted] • Insulin and adipocytokines are important proteins for hippocampal functions. • l -theanine (N-Ethyl- l -glutamine), a soluble amino acid of teas (Camellia Sinensis L.), has health beneficial effects. • l -theanine affects the levels of hippocampal insulin, leptin and adiponectin. [ABSTRACT FROM AUTHOR]

Background: Statins have emerged as a vital therapeutic option for dyslipidemia, effectively reducing morbidity and mortality in individuals with various medical conditions. Recent research has shed light on the intricate pathophysiology of atherosclerosis, which involves lipid accumulation and inflammatory mediators. This research was conducted to assess the correlation between statin therapy and adipocytokine and inflammatory mediator levels in dyslipidemic nondiabetic patients. Methods: A total of 67 dyslipidemic nondiabetic patients were enrolled, alongside 33 healthy controls. The participants were categorized into three groups: Group (A), comprising patients undergoing statin therapy (n = 34), Group (B), consisting of patients not receiving statin therapy (n = 33); and Group (C), comprising healthy controls (n = 33). Results: Patients not receiving statin therapy exhibited significant dyslipidemic profiles compared to patients undergoing statin therapy and healthy controls. Levels of total cholesterol (TC), triglycerides (TG), very low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) were higher in patients not receiving statin therapy. Serum levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) were higher in the statin group than in the non-statin group and controls. Additionally, PCSK9 levels were higher in patients treated with rosuvastatin than those treated with atorvastatin. Conversely, levels of retinol-binding protein 4 (RBP4) were lower in the statin group compared to the non-statin group and controls. Although no significant difference in RBP4 levels between atorvastatin and rosuvastatin users was found, atorvastatin displayed lower RBP4 values. The study also revealed lower C-reactive protein (CRP) levels in the statin group, primarily in the rosuvastatin subgroup, compared to the non-statin group. Conclusion: Statin therapy increased PCSK9 levels, with a more pronounced rise observed in patients treated with rosuvastatin than atorvastatin. Statin therapy proved protective by reducing RBP4 and CRP levels in dyslipidemic nondiabetic patients. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LUAD) is amongst the major contributors to cancer-related deaths on a global scale. Adipocytokines and long non-coding RNAs (lncRNAs) are indispensable participants in cancer. We performed a pan-cancer analysis of the mRNA expression, single nucleotide variation, copy number variation, and prognostic value of adipocytokines. LUAD samples were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Simultaneously, train, internal and external cohorts were grouped. After a stepwise screening of optimized genes through least absolute shrinkage and selection operator regression analysis, random forest algorithm,, and Cox regression analysis, an adipocytokine-related prognostic signature (ARPS) with superior performance compared with four additional well-established signatures for survival prediction was constructed. After determination of risk levels, the discrepancy of immune microenvironment, immune checkpoint gene expression, immune subtypes, and immune response in low- and high-risk cohorts were explored through multiple bioinformatics methods. Abnormal pathways underlying high- and low-risk subgroups were identified through gene set enrichment analysis (GSEA). Immune-and metabolism-related pathways that were correlated with risk score were selected through single sample GSEA. Finally, a nomogram with satisfied predictive survival probability was plotted. In summary, this study offers meaningful information for clinical treatment and scientific investigation.

Objectives: Adipocytokines and oxidative stress (OS) are involved in the pathogenesis of both obesity and periodontitis. The aim of this study was to evaluate periodontal therapy outcomes in terms of serum and gingival crevicular fluid (GCF) levels of adipocytokines and OS markers in obese patients with periodontitis, in order to have an insight into the association between obesity and periodontitis. Materials and methods: A total of 39 patients (20 obese, 19 non-obese) with periodontitis were included in this study. Clinical periodontal parameters were assessed; serum and GCF levels of adipocytokines and OS markers were evaluated by ELISA at baseline and 3 months after non-surgical periodontal therapy. Results: Significant improvements in clinical periodontal parameters were observed in both groups at 3 months (p < 0.01). While serum levels of TNF-α, leptin, and total oxidant status (TOS) in the obese group were higher at baseline (p < 0.01), leptin levels remained higher at 3 months despite a significant decrease (p < 0.01). Although NSPT improved GCF levels of total antioxidant status (TAS) and TOS in both groups, they were significantly different between the groups after therapy (p < 0.05). Conclusions: It seems that leptin, TNF-α, and TOS contribute to systemic inflammatory and oxidative state in patients with obesity. Despite improvements in clinical periodontal parameters, obesity might be a modulating factor in the development and progression of periodontal disease in terms of some adipocytokines and OS markers. Clinical relevance: Since the global burden of both obesity and periodontitis is continuously increasing, the management of these inflammatory diseases has become more important. The current study contributes to our understanding of the role of OS and adipocytokines on the relationship between obesity and periodontitis by response to periodontal treatment. [ABSTRACT FROM AUTHOR]

Background. The study aimed to detect the serum levels of fibroblast growth factor-21 (FGF-21) in fatty pancreas (FP) patients and to investigate their potential clinical value. Methods. We screened patients with FP using transabdominal ultrasound. The anthropometric, biochemical and serum levels of FGF-21 were compared between the FP group and the normal control (NC) group. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum FGF-21 for FP patients. Results. Compared with the NC group, body mass index, fasting blood glucose levels, uric acid levels and cholesterol levels of the FP group were significantly higher, while the high-density lipoprotein level was lower. In addition, levels of serum FGF-21, resistin, leptin and tumor necrosis factor-κ were significantly higher than those in theNCgroup, while the serum adiponectin level was lower. Pearson analysis showed serum FGF-21 levels in FP patients were negatively correlated with leptin. The ROC curve showed the best critical value of the serum FGF-21 level in FP patients was 171 pg/mL (AUC 0.744, P = 0:002, 95% confidence intervals 0.636-0.852). Conclusion. Serum FGF-21 was closely related to fatty pancreas. Detecting serum FGF-21 levels may help identify the population susceptible to FP. [ABSTRACT FROM AUTHOR]

Hypertension is one of the major risk factors for cardiovascular diseases and is caused by various abnormalities including the contractility of blood vessels. Spontaneously hypertensive rats (SHR), whose systemic blood pressure increases with aging, are a frequently used animal model for investigating essential hypertension and related complications in humans due to the damage of several organs. Human omentin-1 is an adipocytokine consisting of 313 amino acids. Serum omentin-1 levels decreased in hypertensive patients compared with normotensive controls. Furthermore, omentin-1 knockout mice showed elevated blood pressure and impaired endothelial vasodilation. Taken together, we hypothesized that adipocytokine, human omentin-1 may improve the hypertension and its complications including heart and renal failure in the aged SHR (65–68-weeks-old). SHR were subcutaneously administered with human omentin-1 (18 μg/kg/day, 2 weeks). Human omentin-1 had no effect on body weight, heart rate, and systolic blood pressure in SHR. The measurement of isometric contraction revealed that human omentin-1 had no influence on the enhanced vasocontractile or impaired vasodilator responses in the isolated thoracic aorta from SHR. On the other hand, human omentin-1 tended to improve left ventricular diastolic failure and renal failure in SHR. In summary, human omentin-1 tended to improve hypertensive complications (heart and renal failure), while it had no influence on the severe hypertension in the aged SHR. The further study of human omentin-1 may lead to the development of therapeutic agents for hypertensive complications. [ABSTRACT FROM AUTHOR]

Obesity is closely associated with an increased risk for metabolic and cardiovascular diseases. Adipose tissue produces a number of secretory bioactive substances, also known as adipocytokines or adipokines, which directly affect adjacent or distant organs. Most adipocytokines are pro-inflammatory, thereby promoting the obesity-linked disorders. In contrast, there are a small number of adipocytokines that exhibit anti-inflammatory properties. It is now recognized that dysregulated production or secretion of adipocytokines caused by adipocyte dysfunction leads to the development of obesity-linked complications. In this review, we focus on the functional role of several adipocytokines in metabolic and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Ischemia with non-obstructive coronary artery (INOCA) is a blind spot of coronary artery disease (CAD). Such patients are often reassured but offered no specific care, that lead to a heightened risk of adverse cerebrovascular disease (CVD) outcomes. Epicardial adipose tissue (EAT) is proven to correlate independently with CAD and its severity, but it is unknown whether EAT is a specific and sensitive indicator of INOCA. This review focuses on the INOCA epidemiology and related factors, as well as the association between EAT [ABSTRACT FROM AUTHOR]

The serum adiponectin/leptin ratio (A/L ratio) is a surrogate marker of insulin sensitivity. Pre-eclampsia (PE) is associated with maternal metabolic syndrome and occasionally impaired fetal growth. We assessed whether the A/L ratio in first-trimester maternal serum was associated with PE and/or birth weight. Adiponectin and leptin were quantitated in first-trimester blood samples (gestational week 10+3–13+6) from 126 women who later developed PE with proteinuria (98 mild PE; 21 severe PE; 7 HELLP syndrome), and 297 controls, recruited from the Copenhagen First-Trimester Screening Study. The A/L ratio was reduced in PE pregnancies, median 0.17 (IQR: 0.12–0.27) compared with controls, median 0.32 (IQR: 0.19–0.62) (p < 0.001). A multiple logistic regression showed that PE was negatively associated with log A/L ratio independent of maternal BMI (odds ratio = 0.315, 95% CI = 0.191 to 0.519). Adiponectin (AUC = 0.632) and PAPP-A (AUC = 0.605) were negatively associated with PE, and leptin (AUC = 0.712) was positively associated with PE. However, the A/L ratio was a better predictor of PE (AUC = 0.737), albeit not clinically relevant as a single marker. No significant association was found between A/L ratio and clinical severity of pre-eclampsia or preterm birth. PE was associated with a significantly lower relative birth weight (p < 0.001). A significant negative correlation was found between relative birth weight and A/L ratio in controls (β = −0.165, p < 0.05) but not in PE pregnancies), independent of maternal BMI. After correction for maternal BMI, leptin was significantly associated with relative birth weight (β = 2.98, p < 0.05), while adiponectin was not significantly associated. Our findings suggest that an impairment of the A/L ratio (as seen in metabolic syndrome) in the first trimester is characteristic of PE, while aberrant fetal growth in PE is not dependent on insulin sensitivity, but rather on leptin-associated pathways. [ABSTRACT FROM AUTHOR]

Background : Adipose tissue is a dynamic endocrine organ that plays a key role in regulating metabolic homeostasis. Previous studies confirmed that bisphenol A (BPA) or fructose can interfere with the function of adipose tissue. Nonetheless, knowledge on how exposure to BPA and fructose impacts energy metabolism in adipose tissue remains limited. Purpose : To determine impact of combined chronic exposure to low-dose bisphenol A and fructose on serum adipocytokines and the energy target metabolome in white adipose tissue. Method : 57 energy metabolic intermediates in adipose tissue and 7 adipocytokines in serum from Sprague Dawley rats were examined after combined exposure to two levels of BPA (lower dose: 0.25, and higher dose: 25 μg/kg every other day) and 5% fructose for 6 months. Results : combined exposure to lower-dose BPA and fructose significantly increased omentin-1, pyruvic acid, adenosine triphosphate (ATP), adenosine monophosphate (AMP), inosine monophosphate (IMP), inosine, and l-lactate; however, these parameters were not significantly affected by higher-dose BPA combined with fructose. Interestingly, the level of succinate (an intermediate of the citric acid cycle) increased dose-dependently in adipose tissue, and the level of apelin 13 (a versatile adipocytokine) decreased dose-dependently in serum after combined exposure to BPA and fructose. Phosphoenolpyruvic acid, phenyl-lactate, and ornithine were significantly correlated with asprosin, omentin-1, apelin, apelin 13, and adiponectin, while l-tyrosine was significantly correlated with irisin and a-FABP under combined exposure to BPA and fructose. Conclusions : these findings indicated that lower-dose BPA combined with fructose could amplify the impact on glycolysis, energy storage, and purine nucleotide biosynthesis in adipose tissue, and adipocytokines, such as omentin-1 and apelin 13, may be related to metabolic interference induced by BPA and fructose exposure. [ABSTRACT FROM AUTHOR]

Ischemia with non-obstructive coronary artery (INOCA) is a blind spot of coronary artery disease (CAD). Such patients are often reassured but offered no specific care, that lead to a heightened risk of adverse cerebrovascular disease (CVD) outcomes. Epicardial adipose tissue (EAT) is proven to correlate independently with CAD and its severity, but it is unknown whether EAT is a specific and sensitive indicator of INOCA. This review focuses on the INOCA epidemiology and related factors, as well as the association between EAT.

Lung adenocarcinoma (LUAD) is amongst the major contributors to cancer-related deaths on a global scale. Adipocytokines and long non-coding RNAs (lncRNAs) are indispensable participants in cancer. We performed a pan-cancer analysis of the mRNA expression, single nucleotide variation, copy number variation, and prognostic value of adipocytokines. LUAD samples were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Simultaneously, train, internal and external cohorts were grouped. After a stepwise screening of optimized genes through least absolute shrinkage and selection operator regression analysis, random forest algorithm,, and Cox regression analysis, an adipocytokine-related prognostic signature (ARPS) with superior performance compared with four additional well-established signatures for survival prediction was constructed. After determination of risk levels, the discrepancy of immune microenvironment, immune checkpoint gene expression, immune subtypes, and immune response in low- and high-risk cohorts were explored through multiple bioinformatics methods. Abnormal pathways underlying high- and low-risk subgroups were identified through gene set enrichment analysis (GSEA). Immune-and metabolism-related pathways that were correlated with risk score were selected through single sample GSEA. Finally, a nomogram with satisfied predictive survival probability was plotted. In summary, this study offers meaningful information for clinical treatment and scientific investigation. [ABSTRACT FROM AUTHOR]

Obesity is associated with mild chronic inflammation, frequently observed along with increased platelet and white blood cell (WBC) levels in adults. We aimed to clarify the relationship between peripheral blood cell count, body mass index standard deviation score (BMI-SDS), and adipocytokine levels in obese adolescents. Participants included 31 patients with obesity (age: 13.1 ± 3.1 yr) and 28 normal-weight controls (age: 13.3 ± 1.9 yr). Obesity was defined as a percentage of overweight ≥ 20%; patients with type 2 diabetes were excluded. As sex differences were observed in blood cell counts, the analysis was performed after adjusting for sex differences. The obese group has significantly higher WBC, red blood cell, and platelet counts, as well as high serum leptin levels and Homeostasis Model Assessment of insulin resistance (HOMA-IR) scores compared with those of the control group. In all participants, BMI-SDS significantly correlated with WBC and platelet counts. Platelet count correlated with serum leptin and glucose levels, whereas WBC count correlated with serum leptin, insulin, HOMA-IR, and glucose levels. Statistical analysis showed that serum leptin level significantly influenced the platelet count and HOMA-IR score affected WBC count. Increased platelet and WBC counts in adolescents with obesity may increase the risk of thrombosis., Competing Interests: None of the authors has any potential conflicts of interest associated with this research., (2024©The Japanese Society for Pediatric Endocrinology.)

The increasing prevalence of obesity has prompted intensive research into understanding its role in pathogenesis and designing appropriate treatments. To determine the signals generated from the interaction of fat cells with a target organ, a reliable white adipocyte model in vitro is needed. Differentiated fibroblasts are the most extensively studied using in vitro cell models of white adipocytes. However, it can be argued that differentiated fibroblasts minimally recapitulate the consequences of obesity. Here, we describe 3T3-L1 MBX cells as a culture model for studying obese adipocytes and their effects. Differentiation of 3T3-L1 MBX cells was at first optimized and then maintained in the presence of fatty acids cocktail combination to induce the obese condition. Lipid accumulation and adipokine secretion profiles were analyzed. Results showed that fatty acid-maintained, differentiated 3T3-L1 MBX cells had significantly greater accumulation of lipids and significant changes in the adipokine secretions in comparison to differentiated 3T3-L1 MBX cells maintained in medium without fatty acids. To elucidate the molecular changes associated with adipogenesis and lipid accumulation profile of 3T3-L1 MBX cells, we have also explored the expression of some of the regulatory proteins related to the development and maintenance of adipocytes from the preadipocyte lineage.

It has recently found that adipokines, play a numerous functional roles in inflammation, lipids and glucose metabolism and in the pathogenically conditions such as atherosclerosis and insulin resistance. Therefore, for the first time we aimed the present study to evaluating serum levels of CTRP5 and inflammatory cytokines patients with CAD and T2DM in comparison with controls. This study was done on 44 patients with CAD, 45 type 2 diabetes mellitus (T2DM), 41 CAD + T2DM and 41 controls. Serum levels of TNF-α, IL-6, MCP-1 and CTRP5 were investigated by ELISA method. The CTRP5 levels of all patients groups were lower in comparison with control group. There was a significant negative relationship between CTRP5 levels and cytokines concentration in the studied patients. Our findings suggested a potential role of CTRP5 in inflammatory process of underlying atherosclerosis and diabetes; however, more studies are needed to support these finding. [ABSTRACT FROM AUTHOR]

Objective·To explore the level of adiponectin in the peripheral blood plasma of patients with immune thrombocytopenia (ITP) and its effect on the differentiation and maturation of megakaryocytes. Methods·From January 2021 to February 2022, the peripheral blood samples were collected from 46 ITP patients in the Department of Hematology, The First Affiliated Hospital of Soochow University and 30 healthy controls with corresponding gender and age in the physical examination center. The plasma adiponectin levels in the ITP patients and healthy control (HC) group were detected by using human adiponectin enzyme-linked immunosorbent assay (ELISA) kits. And the correlation between adiponectin level and body mass index (BMI) in the ITP patients was analyzed. In terms of cell experiments, real-time quantitative PCR (RT-qPCR) and Western blotting were used to study the expression of adiponectin receptors (ADIPOR1 and ADIPOR2) in the myeloid cell line K562, and the megakaryocyte cell lines MEG-01 and Dami at mRNA and protein levels, respectively. The differentiation of K562 cell line and the maturation of MEG-01 and Dami cell lines were induced by phorbol 12-myristate 13-acetate (PMA). At the same time, the cells were treated with different concentrations of adiponectin receptor agonist AdipoRon. Flow cytometry was used to detect the percentage of CD41+ cells, the mean fluorescence intensity (MFI) of CD41, and the proportion of polyploid cells (≥4N). Results·Compared with the HC group, the plasma adiponectin level of the ITP patients significantly increased (P=0.000), and there was no significant correlation between the adiponectin level and the BMI of the patients (P=0.621). RT-qPCR and Western blotting showed that ADIPOR1 and ADIPOR2 were expressed in K562, MEG-01 and Dami cell lines. The proportion of CD41+ cells in the K562 cell line co-cultured with 10 μmol/L or 20 μmol/L AdipoRon and PMA for 72 h were significantly lower than those in the PMA+DMSO group (P= 0.000). The CD41-MFI (P=0.047) and the proportion of polyploid cells (P=0.003) in the MEG-01 cell line co-cultured with 20 μmol/L AdipoRon and PMA for 72 h were significantly higher than those in the PMA+DMSO group; however, in the Dami cell line, no significant increases of both were found after the treatment of 20 μmol/L AdipoRon and PMA. Conclusion·The adiponectin level is elevated in the peripheral blood plasma of ITP patients. Human myeloid cell line K562, and megakaryocyte cell lines MEG-01 and Dami all express adiponectin receptors ADIPOR1 and ADIPOR2. Adiponectin receptor agonists can inhibit megakaryocyte differentiation in vitro, but its effect on megakaryocyte maturation is uncertain. [ABSTRACT FROM AUTHOR]

Shuo Zhang,1 Genxiang Rong,2 Yayun Xu,3 Juehua Jing1 1Department of Orthopedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Juehua JingDepartment of Orthopedics, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, Anhui, 230032, People’s Republic of ChinaEmail jjhhu@sina.comBackground: Adipocytokines have been proven to be involved in the progression of autoimmune diseases, including rheumatoid arthritis (RA). Nesfatin-1, a newly discovered adipokine, has recently been reported to possess potent anti-inflammatory, antiapoptotic, and antioxidative properties. However, its role in RA has not yet been reported. Therefore, this study aimed to determine nesfatin-1 levels in the synovium and synovial fluid (SF) of patients with RA and examine their correlation with clinical manifestations and proinflammatory cytokine levels.Methods: Synovium and SF samples were collected from patients with RA and non-RA patients during joint surgery. Immunohistochemistry was used to measure nesfatin-1 protein expression in the synovium. Enzyme-linked immunosorbent assay was used to measure nesfatin-1, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels in the synovium and SF. Pearson correlation analysis was used to evaluate the correlations between nesfatin-1 levels, RA clinical features, and proinflammatory cytokines. The diagnostic value of synovium nesfatin-1 for RA was assessed using receiver operating characteristic (ROC) curve analysis.Results: The results showed that nesfatin-1, IL-1β, and TNF-α levels in the synovium were significantly higher in patients with RA than in controls, with age and body mass index as covariates. Moreover, the results of Pearson correlation analysis showed that nesfatin-1 levels were positively correlated with IL-1β and TNF-α levels in the synovium of patients with RA. Furthermore, there was a positive relationship between synovium nesfatin-1 levels and rheumatoid factor in patients with RA. Additionally, the results of the ROC curve analysis revealed an area under the curve of 0.733 with 77.5% sensitivity and 60.0% specificity for synovium nesfatin-1 in discriminating patients with RA from controls.Conclusion: These findings suggest that increased nesfatin-1 levels in the synovium may be associated with proinflammatory cytokines and RA severity.Keywords: rheumatoid arthritis, adipocytokine, nesfatin-1, synovium, synovial fluid, pro-inflammatory cytokines

Visfatin reportedly induces the expression of proinflammatory cytokines. Severe grades of intervertebral disc disease (IVDD) exhibit higher expression of visfatin than mild ones. However, the direct relationship between visfatin and IVDD remains to be elucidated. This study aimed to clarify whether stimulation of visfatin in IVDD is mediated by IL-6. To investigate the role of visfatin in IVDD, a rat model of anterior disc puncture was established by injecting visfatin or PBS using a 27-gauge needle. Results revealed an obvious aggravation of the histological morphology of IVDD in the visfatin group. On treating human NP cellswith visfatin, the levels of collagenII and aggrecan decreased and those of matrix metallopeptidase 3 and IL-6 gradually increased. A rapid increase in ERK, JNK, and p38 phosphorylation was also noted after visfatin treatment. Compared to those treated with visfatin alone, NP cells pretreated with ERK1/2, JNK, and p38 inhibitors or siRNA targeting p38, ERK, and JNK exhibited a significant suppression of IL-6. Our data represent the first evidence that visfatin promotes IL-6 expression in NP cells via the JNK/ERK/p38-MAPK signalling pathways. Further, our findings suggest epidural fat and visfatin as potential therapeutic targets for controlling IVDD-associated inflammation.

Abstract Background Dietary fatty acid (FA) content has been shown to influence the development of post-traumatic osteoarthritis (PTOA) in obesity. We used the fat-1 transgenic mouse to examine the hypothesis that endogenous reduction of ω-6 to ω-3 FA ratio, under the same dietary conditions, would mitigate metabolic inflammation and the pathogenesis of PTOA in obese male and female mice. Methods Male and female fat-1 and wild-type littermates were fed either a control diet or an ω-6 FA-rich high-fat diet and underwent destabilization of the medial meniscus (DMM) surgery to induce PTOA. OA severity, synovitis, and osteophyte formation were determined histologically, while biomarker and lipidomic analyses were performed to evaluate levels of adipokines, insulin, pro-/anti-inflammatory cytokines, and FAs in serum and joint synovial fluid. Multivariable models were performed to elucidate the associations of dietary, metabolic, and mechanical factors with PTOA. Results We found that elevated serum levels of ω-3 FAs in fat-1 mice as compared to wild-type controls fed the same diet resulted in reduced OA and synovitis in a sex- and diet-dependent manner, despite comparable body weights. The fat-1 mice showed trends toward decreased serum pro-inflammatory cytokines and increased anti-inflammatory cytokines. Multivariable analysis for variables predicting OA severity in mice resulted in correlations with serum FA levels, but not with body weight. Conclusions This study provides further evidence that circulating FA composition and systemic metabolic inflammation, rather than body weight, may be the major risk factor for obesity-associated OA. We also demonstrate the potential genetic use of ω-3 FA desaturase in mitigating PTOA in obese patients following injury.

BackgroundThe survival rate of children and adolescents with acute lymphoblastic leukemia (ALL) has progressively improved. However, ALL survivors often have adverse effects after treatment, such as an increased risk of obesity. Obesity has been associated with reduced survival.ObjectiveWe investigated the relationship between obesity, adipocytokine levels, and ALL short-term outcomes.MethodsWeight and height were measured, and body mass index (BMI) was calculated at patient diagnosis and discharge. Leptin and Adiponectin levels and Minimal Residual Disease (MRD) were measured before therapy, at days 19 of remission-induction therapy, and at the end of remission-induction therapy (days 46). The relationship between BMI, adipocytokine levels, and MRD was then determined.ResultsCompared to the normal BMI group, children with an abnormal increase in BMI had an increase in MRD at day 19 and 46 (P = 0.04 and P = 0.008), and showed a positive correlation (P = 0.014). In addition, we found a positive correlation between weight, hip circumference at diagnosis and at day 19, and MRD at day 46. Both BMI and fat concentric distribution affected the outcome of ALL children. A higher BMI was also associated with a significant increase in Leptin levels at diagnosis. Leptin resistance should be considered in ALL children with high BMI.ConclusionBMI affects the outcome of ALL patients. Early interventions such as regular weight, height monitoring, and dietary assessments should be preferably initiated during remission-induction chemotherapy.

The serum adiponectin/leptin ratio (A/L ratio) is a surrogate marker of insulin sensitivity. Pre-eclampsia (PE) is associated with maternal metabolic syndrome and occasionally impaired fetal growth. We assessed whether the A/L ratio in first-trimester maternal serum was associated with PE and/or birth weight. Adiponectin and leptin were quantitated in first-trimester blood samples (gestational week 10+3–13+6) from 126 women who later developed PE with proteinuria (98 mild PE; 21 severe PE; 7 HELLP syndrome), and 297 controls, recruited from the Copenhagen First-Trimester Screening Study. The A/L ratio was reduced in PE pregnancies, median 0.17 (IQR: 0.12–0.27) compared with controls, median 0.32 (IQR: 0.19–0.62) (p < 0.001). A multiple logistic regression showed that PE was negatively associated with log A/L ratio independent of maternal BMI (odds ratio = 0.315, 95% CI = 0.191 to 0.519). Adiponectin (AUC = 0.632) and PAPP-A (AUC = 0.605) were negatively associated with PE, and leptin (AUC = 0.712) was positively associated with PE. However, the A/L ratio was a better predictor of PE (AUC = 0.737), albeit not clinically relevant as a single marker. No significant association was found between A/L ratio and clinical severity of pre-eclampsia or preterm birth. PE was associated with a significantly lower relative birth weight (p < 0.001). A significant negative correlation was found between relative birth weight and A/L ratio in controls (β = −0.165, p < 0.05) but not in PE pregnancies), independent of maternal BMI. After correction for maternal BMI, leptin was significantly associated with relative birth weight (β = 2.98, p < 0.05), while adiponectin was not significantly associated. Our findings suggest that an impairment of the A/L ratio (as seen in metabolic syndrome) in the first trimester is characteristic of PE, while aberrant fetal growth in PE is not dependent on insulin sensitivity, but rather on leptin-associated pathways.

Periodontitis is associated with numerous systemic diseases, and it has been shown that these associations are partly causal in nature. It is assumed that such interactions between periodontal and systemic diseases are also medi- ated via adipokines. Apelin, an adipokine about which there is little research in the dental field, is also produced together with its receptor in periodontal cells. The aim of this review was to summarize the currently available literature on the apelin-APJ system to better understand the pathomechanistic relationship between periodontitis and obesity and to de- termine the potential clinical relevance of apelin for diagnostics and therapy. In vitro studies suggest that apelin can en- hance bacterial-induced synthesis of proinflammatory and proteolytic molecules, indicating a significant etiopathogenic role of this adipokine. Since serum levels of apelin are elevated in diabetes and/or obesity, it is possible that such sys- temic diseases promote the development and progression of periodontitis via apelin. On the other hand, it is also conceivable that apelin from the periodontium influences such systemic diseases. Further research is needed to better understand the role of apelin in the periodontium and the entire oral cavity, but also in the interactions between periodontal and sys- temic diseases. In particular, clinical intervention studies are needed to further decipher the etiopathogenic role of apelin in periodontitis.

Resistin is one of the most important adipokines, and its role lies mainly in controlling insulin sensitivity and inflammation. However, over the last years, the study of resistin gained increased popularity since it was proved that there is a considerable relationship between high levels of resistin and obesity as well as obesity-induced diseases, including diabetes, cardiovascular disorders, and cancer. Regarding cancer risk, circulating resistin levels have been correlated with several types of cancer, including colorectal, breast, lung, endometrial, gastroesophageal, prostate, renal, and pancreatic cancer. Colorectal cancer is regarded as a multi-pathway disease. Several pathophysiological features seem to promote colorectal cancer (CRC) such as chronic inflammation, insulin resistance, and obesity. Even though the molecular mechanisms involved in CRC development remain rather vague, it is widely accepted that several biochemical factors promote CRC by releasing augmented pro-inflammatory cytokines, like IGF-I, insulin, sex-steroid hormones, and adipokines. A wide range of research studies has focused on evaluating the impact of circulating resistin levels on CRC risk and determining the efficacy of chemotherapy in CRC patients by measuring resistin levels. Moreover, significant outcomes have emerged regarding the association of specific single nucleotide polymorphisms (SNPs) in the resistin gene and CRC risk. The present study reviewed the role of circulating resistin levels in CRC development and shed light on specific resistin gene SNPs implicated in the disease's development. Finally, we analyzed the impact of resistin levels on the effectiveness of chemotherapy and further discussed whether resistin can be regarded as a valuable biomarker for CRC prognosis and treatment. Resistin is one of the most important adipokines, and its role lies mainly in controlling insulin sensitivity and inflammation. However, over the last years, the study of resistin gained increased popularity since it was proved that there is a considerable relationship between high levels of resistin and obesity as well as obesity-induced diseases, including diabetes, cardiovascular disorders, and cancer. This review discusses the aberrant expression of resistin and its receptors, its diverse downstream signaling, and its impact on tumor growth, metastasis, angiogenesis, and therapy resistance to support its clinical exploitation in biomarker and therapeutic development., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Rompou et al.)

Visfatin reportedly induces the expression of proinflammatory cytokines. Severe grades of intervertebral disc disease (IVDD) exhibit higher expression of visfatin than mild ones. However, the direct relationship between visfatin and IVDD remains to be elucidated. This study aimed to clarify whether stimulation of visfatin in IVDD is mediated by IL-6. To investigate the role of visfatin in IVDD, a rat model of anterior disc puncture was established by injecting visfatin or PBS using a 27-gauge needle. Results revealed an obvious aggravation of the histological morphology of IVDD in the visfatin group. On treating human NP cellswith visfatin, the levels of collagenII and aggrecan decreased and those of matrix metallopeptidase 3 and IL-6 gradually increased. A rapid increase in ERK, JNK, and p38 phosphorylation was also noted after visfatin treatment. Compared to those treated with visfatin alone, NP cells pretreated with ERK1/2, JNK, and p38 inhibitors or siRNA targeting p38, ERK, and JNK exhibited a significant suppression of IL-6. Our data represent the first evidence that visfatin promotes IL-6 expression in NP cells via the JNK/ERK/p38-MAPK signalling pathways. Further, our findings suggest epidural fat and visfatin as potential therapeutic targets for controlling IVDD-associated inflammation. [ABSTRACT FROM AUTHOR]

Abdominal massage (AM), a traditional Chinese medicine-based treatment method, has received considerable attention in the recent years. The aim of the present study was to investigate the effect of AM on high-fat diet (HFD)-induced insulin resistance (IR) in comparison with resveratrol (RSV) treatment. Forty-eight male Sprague-Dawley rats were randomly divided into the following four groups: standard chow diet (control group), high-fat diet (model group), HFD + abdominal massage (AM group), and HFD + resveratrol (RSV group). A rat model of IR was established by feeding HFD to rats for 8 weeks followed by treatment with AM or RSV for 4 weeks. The underlying HFD-induced IR molecular mechanisms were studied in rat serum and skeletal muscles. RSV and AM significantly improved glucose intolerance, hyperglycemia, obesity, and significantly reduced lipid accumulation [triglyceride (TC), total cholesterol (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)], adipocytokine [free fatty acids (FFA), adiponectin (ADPN)] and serum pro-inflammatory cytokines (IL-6 and TNF-α) secretion. In addition, AM activated the AMPK/SIRT1 signaling pathway in rat skeletal muscle. In conclusion, our results showed that AM could improve IR by regulating the secretion of adipocytokines, pro-inflammatory cytokines as well as related signaling pathways in the skeletal muscle of rats, which might provide insights into development of new treatment methods for the clinical treatment of IR. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common tumor in women worldwide, and an increasing public health concern. Knowledge of both protective and negative risk factors is essential for a better understanding of this heterogenous disease. We undertook a review of the recent literature and evaluated the relationship between obesity mediators and breast cancer development depending on menopausal status. Excess weight is now pandemic and has replaced tobacco as the main lifestyle-related risk factor for premature death. Although the prevalence of obesity/overweight has increased globally over the last 50 years, the potential harm attributable to excess fat has generally been underestimated. The relationship between overweight/obesity, breast cancer and overall risk appears to be highly dependent on menopausal status. Thus, obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women. We evaluate the role of different clinical factors potentially involved in this seemingly contradictory relationship, including estrogen, mammogram density, adipokines, insulin-signaling pathway activation, and inflammatory status. A key focus of this review is to better understand the impact of body mass index and menopausal status on these clinical factors and, hence, provide some clarity into the inter-relationships involved in this controversial issue.

Visfatin/nicotinamide phosphoribosyltransferase (NAMPT) is an adipokine expressed predominately in visceral fat tissues. High circulating levels of visfatin/NAMPT have been implicated in vascular remodeling, vascular inflammation, and atherosclerosis, all of which pose increased risks of cardiovascular events. In this context, increased levels of visfatin have been correlated with several upregulated pro‐inflammatory mediators, such as IL‐1, IL‐1Ra, IL‐6, IL‐8, and TNF‐α. Furthermore, visfatin is associated with leukocyte recruitment by endothelial cells and the production of adhesion molecules such as vascular cell adhesion molecule 1, intercellular cell adhesion molecule 1, and E‐selectin, which are well known to mediate the progression of atherosclerosis. Moreover, diverse angiogenic factors have been found to mediate visfatin‐induced angiogenesis. These include matrix metalloproteinases, vascular endothelial growth factor, monocyte chemoattractant protein 1, and fibroblast growth factor 2. This review aims to provide a comprehensive overview of the pro‐inflammatory and angiogenic actions of visfatin, with a focus on the pertinent signaling pathways whose dysregulation contributes to the pathogenesis of atherosclerosis. Most importantly, some hypotheses regarding the integration of the aforementioned factors with the plausible atherogenic effect of visfatin are put forth for consideration in future studies. The pharmacotherapeutic potential of modulating visfatin's roles could be important in the management of cardiovascular disease, which continues to be the leading cause of death worldwide. [ABSTRACT FROM AUTHOR]

Background: Whether HAIR-AN syndrome and polycystic ovarian syndrome (PCOS) are distinct entities or represent a phenotypic spectrum of the same syndrome is still unclear. HAIR-AN syndrome is characterized by high insulin resistance, obesity, and hyperinsulinemia as compared to PCOS and could represent adipose tissue dysfunction as the primary pathophysiologic trigger. This study was undertaken to study the role of adipose tissue dysfunction in HAIR-AN syndrome and PCOS using adipocytokines as surrogate markers of "adiposopathy." Materials and Methods: A cross-sectional observational study was conducted at a tertiary care hospital over a period of 1 year. Serum adiponectin, leptin, IL-6, and TNF-α levels were measured in 30 women with HAIR-AN syndrome and in 30 women with PCOS. Correlations between adipocytokines, inflammatory markers, serum testosterone, and serum insulin were determined. Data analysis was performed using the SPSS version 23.0 (IBM SPSS Statistics Inc., Chicago, IL, USA) software program. Results: Women with HAIR-AN syndrome had significantly higher hyperandrogenemia, hyperinsulinemia, and insulin resistance as compared to PCOS women. They also had high leptin levels and lower adiponectin levels (p < 0.001). However, the levels of inflammatory markers (TNF-α and IL-6) were similar in both the groups (p > 0.05). Serum adiponectin showed a negative correlation with HOMA-IR and testosterone levels, while leptin showed a positive correlation with both in HAIR-AN patients while no such correlation was found in the PCOS group. Conclusion: The significantly raised adipocytokines in HAIR-AN syndrome patients as compared to PCOS patients indicates the primary role of adipose tissue dysfunction ("adiposopathy") in the pathogenesis of HAIR-AN syndrome while only a minor role, if any, in PCOS. Both these syndromes stand as distinct entities pathogenically with an overlapping phenotype. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common tumor in women worldwide, and an increasing public health concern. Knowledge of both protective and negative risk factors is essential for a better understanding of this heterogenous disease. We undertook a review of the recent literature and evaluated the relationship between obesity mediators and breast cancer development depending on menopausal status. Excess weight is now pandemic and has replaced tobacco as the main lifestyle-related risk factor for premature death. Although the prevalence of obesity/overweight has increased globally over the last 50 years, the potential harm attributable to excess fat has generally been underestimated. The relationship between overweight/obesity, breast cancer and overall risk appears to be highly dependent on menopausal status. Thus, obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women. We evaluate the role of different clinical factors potentially involved in this seemingly contradictory relationship, including estrogen, mammogram density, adipokines, insulin-signaling pathway activation, and inflammatory status. A key focus of this review is to better understand the impact of body mass index and menopausal status on these clinical factors and, hence, provide some clarity into the inter-relationships involved in this controversial issue. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the possible relationship of serum adiponectin and visfatin levels that are derived from the adipose tissue in patients with juvenile idiopathic arthritis (JIA), in accordance with the routinely used biochemical parameters, to evaluate the management of therapy and assessment of disease activity. Methods: According to the Wallace criteria, the study population was divided into active, remission and control groups. Serum adiponectin and visfatin levels were measured by the enzyme-linked immunosorbent assay method. Complete blood count, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were routinely measured. Neutrophil/lymphocyte ratio (NLR) was calculated. Results: Significant differences were found in serum visfatin levels between the active and the control groups (p<0.05) and in serum adiponectin levels between the active and remission groups (p<0.05). Significant differences were also observed in routinely used parameters, namely; ESR, CRP and platelet count (p<0.05), among the active, remission and control groups, whereas the leukocyte and neutrophil counts together with the percentage of neutrophils, lymphocytes and NLR established significant differences only between the active and control groups (p<0.05). Conclusion: The results suggest that serum visfatin levels may be useful to indicate disease activity in accordance with the correlation between ESR and CRP in patients with JIA. Unlike visfatin, serum adiponectin levels may be utilised in the management of treatment rather than as a diagnostic parameter on the onset of JIA. Although this study included a small sample of patients with JIA, it highlights the potential of the two adipose tissuederived parameters as new biochemical parameters in JIA, both in the assessment of disease activity and the management of treatment, which are essential to improve the life quality of these patients. [ABSTRACT FROM AUTHOR]

Adipokines are key mediators of inflammation in metabolic syndrome perpetuating the effect of excess nutrient intake by setting a self-maintaining vicious circle. Here, we assess levels of adiponectin and leptin in a cohort of individuals with MetS undergoing dietary and behavioral counselling. Specifically, we investigate their role as predictors of metabolic syndrome remission after 1 year. Patients with MetS (n = 127) received behavioral and dietary recommendations and were followed-up for 1 year. Serum was available for 108 individuals, levels of adiponectin and leptin were tested at baseline, at 6 months (t1) and after 1 year (t2). Adiponectin/leptin (A/L) ratio was also calculated and tested for predictive ability. At the end of the follow-up period, 59 patients did not show enough criteria to define MetS anymore. When considered alone, adiponectin and leptin levels did not show difference over follow-up. Their ratio instead was significantly reduced at t1 and t2 with respect to baseline. Remitters also showed lowers level of leptin and A/L ratio as compared to non-remitters at t1. At this timepoint, A/L ratio independently predicted MetS remission at 1 year [OR 9.082 95%CI (1.394–59.160), p = 0.021]. Bootstrap resampling analysis internally validated our findings. Preliminary results from our pilot study suggest that MetS remission after counselling associates with changes in adipokine balance. A/L ratio decreases overtime and its value at 6 months can independently predict MetS remission. • Adipokines are key mediators of inflammation in metabolic syndrome. • Adipokine balance change in individuals with metabolic syndrome after medical counselling. • Adiponectin/leptin ratio might predict metabolic syndrome remission. [ABSTRACT FROM AUTHOR]

Asprosin, coiled-coil domain-containing 80(CCDC80) and angiopoietin-like 4(ANGPTL4) are newly discovered adipocytokine that affects glucose tolerance, insulin resistance and cardiovascular diseases. The goal of this study was to investigate if a relationship exists among asprosin, CCDC80 and ANGPTL4 and inflammatory bowel disease (IBD). Fifty subjects with newly diagnosed IBD and fifty healthy individuals were enrolled. Patients were treated with standard therapies for 3 months. Plasma asprosin, CCDC80 and ANGPTL4 levels were measured with enzyme-linked immunosorbent assay. High resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia (flow-mediated dilation, FMD) and after sublingual glyceryltrinitrate. Compare with healthy individuals, plasma CCDC80, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly higher (p < 0.05, respectively), whereas plasma asprosin, ANGPTL4 levels and FMD were significantly lower in both UC and CD patients (p < 0.05). Plasma CCDC80 levels were significantly higher in patients with CD (p < 0.05), while plasma asprosin and ANGPTL4 levels were lower (pP < 0.05) as compared with those in patients with UC. Standard therapies increased plasma asprosin, ANGPTL4 levels and FMD in both UC and CD (p < 0.05), UC and CD patientswhile decreased plasma CCDC80, ESR, CRP levels and HOMA-IR (p < 0.05). The changes in HOMA-IR and FMD were correlated with the changes in plasma asprosin, CCDC80 and ANGPTL4 levels over the study period (p < 0.05). Plasma asprosin, CCDC80 and ANGPTL4 levels may be applied as a significant marker for early stage of insulin resistance and atherosclerosis in IBD, especially of CD. [ABSTRACT FROM AUTHOR]

Objectives: Non-alcoholic fatty liver disease (NAFLD) has significant genetic susceptibility. Adipocytokines play a crucial role in NAFLD development by participating in insulin resistance and hepatic steatosis. However, the association between adipocytokine pathway genes and NAFLD remains unclear. This study aims to explore the association of gene polymorphisms in the adipocytokine pathway and their interactions with NAFLD in obese children., Methods: A case-control study was conducted, dividing obese children into NAFLD and control groups. Peripheral venous blood (2 mL) was collected from each participant for DNA extraction. A total of 14 single nucleotide polymorphisms (SNP) in the adipocytokine pathway were genotyped using multiplex PCR and high-throughput sequencing. Univariate and multivariate Logistic regression analyses were used to assess the association between SNP and NAFLD in obese children. Dominant models were used to analyze additive and multiplicative interactions via crossover analysis and Logistic regression. Generalized multifactor dimensionality reduction (GMDR) was used to detect gene-gene interactions among the 14 SNPs and their association with NAFLD in obese children., Results: A total of 1 022 children were included, with 511 in the NAFLD group and 511 in the control group. After adjusting for age, gender, and BMI, multivariate Logistic regression showed that PPARG rs1801282 was associated with NAFLD in the obese children in 3 genetic models: heterozygote model (CG vs CC, OR =0.58, 95% CI 0.36 to 0.95, P =0.029), dominant model (GG+CG vs CC, OR =0.62, 95% CI 0.38 to 1.00, P =0.049), and overdominant model (CC+GG vs CG, OR =1.72, 95% CI 1.06 to 2.80, P =0.028). PRKAG2 rs12703159 was associated with NAFLD in 4 genetic models: heterozygous model (CT vs CC, OR =1.51, 95% CI 1.10 to 2.07, P =0.011), dominant model (CT+TT vs CC, OR =1.50, 95% CI 1.10 to 2.03, P =0.010), overdominant model (CC+TT vs CT, OR =0.67, 95% CI 0.49 to 0.92, P =0.012), and additive model (CC vs CT vs TT, OR =1.40, 95% CI 1.07 to 1.83, P =0.015). No significant multiplicative or additive interaction between PPARG rs1801282 and PRKAG2 rs12703159 was found in association with NAFLD. GMDR analysis, adjusted for age, gender, and BMI, revealed no statistically significant interactions among the 14 SNPs (all P >0.05)., Conclusions: Mutations in PPARG rs1801282 and PRKAG2 rs12703159 are associated with NAFLD in obese children. However, no gene-gene interactions among the SNP are found to be associated with NAFLD in obese children.

Obesity is a serious health issue worldwide. Obesity and obesity-associated disease cause endothelial dysfunction, leading to cardiovascular complications. In resistance-size arteries, endothelium-dependent hyperpolarization (EDH) initiated in endothelial cells plays a central role in endothelium-dependent vasodilation, and a number of studies have reported impaired EDH in obese animals and humans. The resulting impairment of EDH in obesity could initiate and accelerate obesity-associated comorbidities such as hypertension and insulin resistance, which ultimately lead to cardiovascular disease. In this review, we present the current knowledge about changes in EDH in obese animals and humans, particularly in studies of diet-induced obese animals. Unlike genetically modified obese animals, diet-induced obese models mimic many features of human obesity. We then explore underlying mechanisms of impaired EDH in diet-induced obesity, with special attention to the role of vascular ion channels.

Accumulating discoveries highlight the importance of interaction between marrow stromal cells and cancer cells for bone metastasis. Bone is the most common metastatic site of breast cancer and bone marrow adipocytes (BMAs) are the most abundant component of the bone marrow microenvironment. BMAs are unique in their origin and location, and recently they are found to serve as an endocrine organ that secretes adipokines, cytokines, chemokines, and growth factors. It is reasonable to speculate that BMAs contribute to the modification of bone metastatic microenvironment and affecting metastatic breast cancer cells in the bone marrow. Indeed, BMAs may participate in bone metastasis of breast cancer through regulation of recruitment, invasion, survival, colonization, proliferation, angiogenesis, and immune modulation by their production of various adipocytokines. In this review, we provide an overview of research progress, focusing on adipocytokines secreted by BMAs and their potential roles for bone metastasis of breast cancer, and investigating the mechanisms mediating the interaction between BMAs and metastatic breast cancer cells. Based on current findings, BMAs may function as a pivotal modulator of bone metastasis of breast cancer, therefore targeting BMAs combined with conventional treatment programs might present a promising therapeutic option.

Background: Obesity is a major risk factor for diabetes mellitus and cardiovascular diseases. Nevertheless, some obese patients have normal parameters of blood arterial pressure, carbohydrate, and lipid metabolism ("metabolically healthy obesity", MHO).Aim: To study adipocytokine levels and to assess the effect of weight loss on cardiometabolic risk factors in patients with metabolically healthy obesity.Materials and methods: We conducted a comparative analysis of the main metabolic parameters and adipocytokine levels in 44 female patients with MHO (according to the IDF criteria of the metabolic syndrome, 2005: obese patients with no more than one additional cardiometabolic risk factor) and in 33 women with metabolically unhealthy obesity (MUHO). We also assessed changes of these indices in the patients who reduced their body weight by ≥ 5% at 6 months.Results: At baseline, body mass index (BMI) and the levels of basal insulin, C-reactive protein (CRP), tumor necrosis factor alfa (TNF-α), adiponectin and retinol-binding protein-4 (RBP-4) in the MHO and MUHO groups were comparable. A significant difference between these groups was observed for the HOMA index (3.0 and 4.4, respectively; p < 0.05), alanine aminotransferase (ALT) (23.49 and 37.39 U/l; p = 0.001), interleukin-6 (0.76 and 1.5 pg/ml; p < 0.05), chemerin (322.4 and 369.2 ng/ml; p < 0.05), and the duration of obesity (18 and 22.6 years; p < 0.05). At 6 months, in those MHO patients, who reduced body weight by ≥ 5% of the initial (66%), there was a significant increase of adiponectin by 4.54 ± 0.83 µg/ml (p < 0.05) and a reduction of waist circumference (WC) by -8.6 ± 1 cm (p > 0.05), НОМА index by -1.13 ± 0.42 (p < 0.05), CRP by -1.7 ± 0.4 mg/l (p < 0.05), RBP-4 by 2.9 ± 1.0 ng/ml (p < 0.05), and сhemerin by -46.6 ± 17.0 ng/ml (p < 0.05). In the MHO group, we found a positive correlation between changes in the adiponectin levels and the degree of reduction in body weight (p < 0.01), changes in RBP-4 and WC (p < 0.05), and changes in the levels of interleukin-6 and high-density lipoprotein (p < 0.05).Conclusion: Compared to the complicated obesity, MHO is associated with a shorter disease history, and lower levels of the HOMA index, interleukin-6, and chemerin levels. The body mass decrease in MHO is associated with a decrease in the proinflammatory adipocytokine levels and of the HOMA index that determines the need for treatment of obesity, regardless of its phenotype.

ObjectiveThe purpose of the current study was to compare the circulating levels of visfatin between women with polycystic ovary syndrome (PCOS) and those without PCOS and to assess the correlations between visfatin levels and various parameters.MethodsThis case-control study recruited 74 PCOS patients and 74 age- and body mass index (BMI)-matched controls. Serum visfatin levels were evaluated using the enzyme-linked immunosorbent assay. Women with PCOS were divided into 2 subgroups based on the presence of clinical or biochemical hyperandrogenism. The possible differences in serum visfatin levels between the hyperandrogenic and non-hyperandrogenic groups were also assessed.ResultsVisfatin levels in PCOS patients were similar to those in the controls. However, hyperandrogenic patients had significantly higher mean serum visfatin levels than those in non-hyperandrogenic patients (3.87 ng/mL; 95% confidence intervals [CIs], 3.09–4.85 in hyperandrogenic group vs. 2.69 ng/mL; 95% CIs, 2.06–3.52 in non-hyperandrogenic group; P=0.038). In women with PCOS, visfatin levels positively correlated with BMI (r=0.23; P=0.047) and the log free androgen index (FAI) (r=0.27; P=0.021) and negatively correlated with high-density lipoprotein (HDL) cholesterol levels (r=−0.37; P=0.025). Except for HDL cholesterol levels, these correlations were also observed in controls.ConclusionVisfatin levels in PCOS patients were similar to those in the controls. However, hyperandrogenic patients showed significantly higher serum visfatin levels than those of non-hyperandrogenic patients, and visfatin had a positive linear correlation with FAI in both PCOS patients and controls.

Background: Oxidative stress and alteration of lipid profile due to obesity and overweight is a major risk factor for atherosclerotic plaque or coronary artery disease. Because of antioxidant and lipid lowering potential of saffron, this study investigated weight alteration, lipid profiles, and insulin resistance index in high-calorie diet rats treated with aqueous extract of saffron stigma and petal. Methods: Forty Sprague-Dawley male rats were randomly divided into 8 groups including healthy control, high-fat diet control, nicotinic acid treated, Anethum graveolens treated, and saffron stigma and petal treated groups. Rats received a high-calorie diet for 16 weeks. For treatment, aqueous extract of saffron stigma (40 and 80 mg/kg) and petal (50 and 100 mg/kg) was used once daily for 4 weeks. Afterward, lipid profile, oxidative stress status, and insulin and adiponectin levels were measured using desired kits. Results: There was a significant decrease in the mean weight of the groups receiving saffron stigma and petal compared to control group (P < 0.05). The increased level of insulin hormone in obese group was improved in treated groups especially in the case of saffron stigma. Also, the decreased level of adiponectin was recovered in treated groups. An improvement was seen in oxidative stress markers and lipid profiles in treated groups compared to obesity pair. Conclusions: In this study, a remarkable antioxidant and lipid lowering potential was detected for saffron stigma, which could improve insulin resistance in obese rats. Therapeutic and protective effect of saffron is mainly related to its richness in phenolic compounds. Saffron stigma compared with petal had more notable effect, which could and should be mentioned in pharmaceutical studies. [ABSTRACT FROM AUTHOR]