Effect of non-surgical periodontal treatment on cytokines/adipocytokines levels among periodontitis patients with or without obesity: a systematic review and meta-analysis.

BACKGROUND: The objective of this systematic review and meta-analysis was to evaluate the effects of non-surgical periodontal therapy (NSPT) on inflammatory-related cytokines/adipocytokines in periodontitis patients with or without obesity. METHODS: We followed the preferred reporting items for systematic reviews and meta-analyses statement and registered the study (CRD42022375331) in the Prospective International Register of Systematic Reviews. We screened randomized-controlled trials and controlled clinical trials from six databases up to December 2022. Quality assessment was performed with RoB-2 and ROBINS-I tools for randomized trials and non-randomized trials, respectively. Meta-analysis was carried out using a random-effect model. RESULTS: We included seventeen references in the systematic analysis, and sixteen in the meta-analysis. Baseline results of pro-inflammatory biomarkers, including serum interleukin (IL)-6, serum and gingival crevicular fluid (GCF), tumor necrosis factor (TNF)-a, serum C-reactive protein (CRP)/hs-CRP, and serum and GCF resistin, were higher in obesity subjects than in normal weight subjects. The effect of NSPT with respect to levels of cytokines/adipocytokines, including IL-6, TNF-a, CRP/hs-CRP, resistin, adiponectin, leptin and retinol binding protein 4 (RBP4), were then analyzed in the systematic and meta-analysis. After three months of NSPT, serum (MD = -0.54, CI = -0.62 - -0.46), and GCF (MD = -2.70, CI = -4.77 - -0.63) levels of IL-6, along with the serum RBP4 (MD = -0.39, CI = -0.68-0.10) decreased in periodontitis individuals with obesity. NSPT also improved GCF adiponectin levels after three months (MD = 2.37, CI = 0.29 - 4.45) in periodontitis individuals without obesity. CONCLUSIONS: Obese status altered the baseline levels of cytokines/adipocytokines (serum IL-6, serum and GCF TNF-a, serum CRP/hs-CRP, and serum and GCF resistin). Then NSPT can shift the levels of specific pro-inflammatory mediators and anti-inflammatory mediators in biological fluids, both in obesity and non-obesity individuals. NSPT can reduce serum and GCF IL-6 levels together with serum RBP4 level in individuals with obesity after 3 months, besides, there is no sufficient evidence to prove that obese patients have a statistically significant decrease in the levels of other cytokines compared to patients with normal weight. NSPT can also increase GCF adiponectin level in normal weight individuals after 3 months. Our findings imply the potential ideal follow-up intervals and sensitive biomarkers for clinical bioanalysis in personalized decision-making of effect of NSPT due to patients' BMI value.

Near-roadway air pollution, immune cells and adipokines among obese young adults.

BACKGROUND: Air pollution has been associated with metabolic disease and obesity. Adipokines are potential mediators of these effects, but studies of air pollution-adipokine relationships are inconclusive. Macrophage and T cells in adipose tissue (AT) and blood modulate inflammation; however, the role of immune cells in air pollution-induced dysregulation of adipokines has not been studied. We examined the association between air pollution exposure and circulating and AT adipokine concentrations, and whether these relationships were modified by macrophage and T cell numbers in the blood and AT. METHODS: Fasting blood and abdominal subcutaneous AT biopsies were collected from 30 overweight/obese 18-26 year-old volunteers. Flow cytometry was used to quantify T effector (Teff, inflammatory) and regulatory (Treg, anti-inflammatory) lymphocytes and M1 [inflammatory] and M2 [anti-inflammatory]) macrophage cell number. Serum and AT leptin and adiponectin were measured using enzyme-linked immunosorbent assay (ELISA). Exposure to near-roadway air pollution (NRAP) from freeway and non-freeway vehicular sources and to regional particulate matter, nitrogen dioxide and ozone were estimated for the year prior to biopsy, based on participants' residential addresses. Linear regression models were used to examine the association between air pollution exposures and adipokines and to evaluate effect modification by immune cell counts. RESULTS: An interquartile increase in non-freeway NRAP exposure during 1 year prior to biopsy was associated with higher leptin levels in both serum [31.7% (95% CI: 10.4, 52.9%)] and AT [19.4% (2.2, 36.6%)]. Non-freeway NRAP exposure effect estimates were greater among participants with greater than median Teff/Treg ratio and M1/M2 ratio in blood, and with greater M1 counts in AT. No adipokine associations with regional air pollutants were found. DISCUSSION: Our results suggest that NRAP may increase serum leptin levels in obese young adults, and this association may be promoted in a pro-inflammatory immune cell environment in blood and AT.

Evaluation of adipokine levels in obese women with periodontitis: A cohort study.

PURPOSE: To evaluate the inflammation-related adipokine levels in the body fluids of obese female participants with and without periodontitis using healthy participants as a control group. METHODS: A cohort design study was carried out at Kocaeli University between December 2014 and June 2015. The study sample comprised 25 obese female participants with periodontitis (Group 1), 31 obese female participants without periodontitis (Group 2), and 15 lean female participants with healthy periodontium (Group 3), from whom body mass index, clinical periodontal parameters were measured, and serum, saliva, and gingival crevicular fluid (GCF) samples were collected. The three groups' periodontal parameters and adipokine levels were evaluated and compared, and the primary outcome was the difference in local and systemic adipokine levels between the study groups. RESULTS: In the participants' serum samples, tumor necrosis factor-α (TNF-α) and leptin levels were lower, whereas adiponectin levels were significantly higher in Group 3 than in the obese groups (P< 0.05). In the participants' saliva samples, interleukin-1ß, TNF-α, and resistin levels were lowest in Group 3, but adiponectin was lowest in Group 2 (P< 0.05). In the participants' GCF samples, interleukin-1ß, resistin, and adiponectin levels were higher in Group 1 (P< 0.05). This study showed that the amounts of the adipokines could differ in serum, saliva, and GCF samples from obese female participants with and without periodontitis and from lean female participants with healthy periodontium. CLINICAL SIGNIFICANCE: Periodontal diseases in different severities can affect overall health by altering the amounts of adipokines (IL-1ß, TNF-α, leptin, resistin, and adiponectin) in serum, saliva, and GCF of obese female patients. Clinicians should be aware that periodontal disease can alter inflammatory adipokine levels and may affect other treatment outcomes in obese female patients.

First trimester secreted Frizzled-Related Protein 4 and other adipokine serum concentrations in women developing gestational diabetes mellitus.

BACKGROUND: The aim of this study was to evaluate whether soluble frizzled-related protein 4 (sFRP4) concentration in the first trimester of pregnancy is individually, or in combination with Leptin, Chemerin and/or Adiponectin, associated with the development of gestational diabetes (GDM). METHODS: In a nested case-control study, 50 women with GDM who spontaneously conceived and delivered a live-born infant were matched with a total of 100 uncomplicated singleton control pregnancies based on body mass index (± 2 kg/m2), gestational age at sampling (exact day) and maternal age (± 2 years). In serum samples, obtained between 70-90 days gestational age, sFRP4, Chemerin, Leptin and Adiponectin concentrations were determined by ELISA. Statistical comparisons were performed using univariate and multi-variate logistic regression analysis after logarithmic transformation of the concentrations. Discrimination of the models was assessed by the area under the curve (AUC). RESULTS: First trimester sFRP4 concentrations were significantly increased in GDM cases (2.04 vs 1.93 ng/ml; p<0.05), just as Chemerin (3.19 vs 3.15 ng/ml; p<0.05) and Leptin (1.44 vs 1.32 ng/ml; p<0.01). Adiponectin concentrations were significantly decreased (2.83 vs 2.94 ng/ml; p<0.01) in GDM cases. Further analysis only showed a weak, though significant, correlation of sFRP4 with Chemerin (R2 = 0.124; p<0.001) and Leptin (R2 = 0.145; p<0.001), and Chemerin with Leptin (R2 = 0.282; p<0.001) in the control group. In a multivariate logistic regression model of these four markers, only Adiponectin showed to be significantly associated with GDM (odds ratio 0.12, 95%CI 0.02-0.68). The AUC of this model was 0.699 (95%CI 0.605-0.793). CONCLUSION: In the first trimester of pregnancy, a multi-marker model with sFRP4, Leptin, Chemerin and Adiponectin is associated with the development of GDM. Therefore, this panel seems to be an interesting candidate to further evaluate for prediction of GDM in a prospective study.

N-glycan structures of target cancer biomarker characterized by two-dimensional gel electrophoresis and mass spectrometry.

Glycoproteins are important biomarkers for cancers, while most glycoproteomics biomarkers suffering from low sensitivity and specificity due to their uncharacterized glycan structures. AZGP1 is a potential biomarker for salivary diagnostics of lung cancer, which is used as a model glycoprotein in this study for method development. We initially analyzed salivary N-glycoproteome by using lectin affinity chromatography and more than 300 N-glycoproteins were identified, including AZGP1. 7 gel spots of AZGP1 were resolved by two-dimensional gel electrophoresis and further confirmed by two-dimensional western blot as well as mass spectrometry. The isomeric glycan structures of AZGP1 in these spots were systematically characterized both at composition level and at structure level. Our results revealed 10 glycan compositions for salivary AZGP1, including core fucosylated glycans on Asn128 and sialylated glycans on Asn109 and Asn112. We further compared the glycan structures of salivary AZGP1 from lung cancer group and control group. Accordingly, 14 and 7 potential glycan structures were successfully revealed, respectively. In total, 15 glycan compositions and 22 potential glycan structures were identified and characterized for AZGP1, including some different structures with the same compositions. In particular, 5 potential glycan structures were identified as lung cancer unique signatures. Our developed strategy holds promise for thorough identification of glycan structures on a target glycoprotein biomarker. In-depth characterization of its glycan structures will ultimately enhance its sensitivity and specificity for cancer detection.

Adipocytokine expression, platelet-to-lymphocyte ratio and TGF-ß1/Smad signaling activity in diabetic patients complicated with pulmonary infection.

OBJECTIVE: To investigate adipocytokine expression levels, platelet-to-lymphocyte ratio (PLR) and transforming growth factor (TGF)-ß1/Smad signaling activity in diabetic patients with pulmonary infection. METHODS: Eighty-two type 2 diabetic patients with pulmonary infection were included in the observation group and 75 patients with simple type 2 diabetes were recruited into the control group. The fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and PLR in the two groups were compared. Complement-C1q/tumor necrosis factor related protein 3 (CTRP-3), complement-C1q/tumor necrosis factor related protein 9 (CTRP-9), leptin, adiponectin, and TGF-ß1/Smad signaling pathway activity in peripheral blood mononuclear cells (PBMCs) was detected. RESULTS: Compared with patients in the control group, patients in the observation group presented with increased levels of FGB, HbA1c, and leptin, an increase in the PLR, and decreased serum CTRP-3, CTRP-9, and adiponectin levels. TGF-ß1, p-Smad2, and p-Smad3 protein expression levels were up-regulated in PBMCs from patients in the observation group compared with the control group. CONCLUSIONS: These results show that in type 2 diabetic patients with pulmonary infection, adipocytokine expression is altered, PLR is disturbed, and the TGF-ß1/Smad signaling pathways in PBMCs are significantly activated.

Biomarkers of vascular disease in diabetes: the adipose-immune system cross talk.

Experimental and clinical studies aimed at investigating the mechanism(s) underlying vascular complications of diabetes indicate that a great number of molecules are involved in the pathogenesis of these complications. Most of these molecules are inflammatory mediators or markers generated by immune or adipose tissue. Some of them, i.e. resistin and sortilin, have been shown to be involved in the cross talk between adipocytes and inflammatory cells. This interaction is an attractive area of research, particularly in type 2 diabetes and obesity. Other proteins, such as adiponectin and visfatin, appear to be more promising as possible vascular markers. In addition, some molecules involved in calcium/phosphorus metabolism, such as klotho and FGF23, have an involvement in the pathogenesis of diabetic vasculopathy, which appears to be dependent on the degree of vascular impairment. Inflammatory markers are a promising tool for treatment decisions while measuring plasma levels of adipokines, sortilin, Klotho and FGF23 in adequately sized longitudinal studies is expected to allow a more precise characterization of diabetic vascular disease and the optimal use of personalized treatment strategies.

Ctrp4, a new adipokine, promotes the differentiation of osteoblasts.

Recent evidence suggests that adipokines are involved in the regulation of bone metabolism. Ctrp4 is a newly discovered member of the adipokine CTRP family. Studies have shown that Ctrp4 is involved in the regulation of tumor cell inflammatory signaling pathways and acts on the hypothalamus to regulate food intake, but its role in osteoblasts is not yet clear. In this study, we found that the expression of Ctrp4 in bone tissue was significantly decreased in the tail-suspended mouse, while that in ovariectomized-simulated osteoporosis mice decreased similarly, indicating that Ctrp4 was involved in osteogenesis regulation. We further isolated Alp-positive osteoblasts from the femur of tail-suspended rats and confirmed that the expression of Ctrp4, Bglap and Alp was down-regulated in the process of bone loss caused by tail suspension. In the process of inducing osteoblastic differentiation in vitro, Ctrp4 interfering significantly inhibited the expression of Alp and Bglap. In addition, inhibition of Ctrp4 resulted in decreased alkaline phosphatase expression and less alizarin red staining, indicating that Ctrp4 promoted osteogenic differentiation and osteoblasts mineralization. In conclusion, our results suggest that Ctrp4 is involved in bone metabolism regulation and promotes osteoblast differentiation, which may become a potential target for future intervention in bone metabolic diseases.

Localization and expression of CTRP6 in ovary and its regulation by FSH in porcine granulosa cells.

C1q/tumor necrosis factor-related protein 6 (CTRP6) is a newly identified adiponectin paralog with modulating effects on metabolism and inflammation. CTRP6 transcript is detected in human ovarian tissue. However, the expression pattern and function of CTRP6 on ovary have been rarely studied. In the present study, we preliminarily examined the structure feature and function of CTRP6 in porcine granulosa cells. The results indicated that the signaling peptide of CTRP6 was located at among positions 21 and 22, and the phosphorylation sites were at 15 (Ser), 4 (Thr) and 4 (Tyr), respectively. Meanwhile, CTRP6 was extremely homologous in livestock and chiropteran. The qPCR results showed that CTRP6 was moderately expressed in porcine follicle. Immunohistochemistry manifested that CTRP6 was presented in various types of ovarian cells. Immunofluorescence revealed that CTRP6 was located in cytoplasm in primary porcine granulosa cells. ELISA results showed that the concentration of CTRP6 in the follicular fluid was gradually decreased with the growth of antral follicle. In addition FSH increased CTRP6 expression levels in a time- and dose-dependent manner in primary porcine granulosa cells, while LH had no effect on CTRP6 basal gene expression, which suggesting CTRP6 is an FSH-responsive gene in porcine granulosa cells. Our findings imply that the CTRP6 may be a candidate gene to regulate folliculogenesis and reproductive performance.

The Adipokine Profile and the Cardiometabolic Risk in Non-Obese Young Adults

Background: Young, non-obese adults are considered at low risk for cardiometabolic diseases, although markers of an unhealthy metabolic state are not uncommon findings in this population. Adipose tissue dysfunction, evaluated by the adipokine profile, significantly influences lipid and glucose metabolism and low-grade systemic inflammation. Aims: To determine the relation between adipose tissue dysfunction and the already confirmed cardiometabolic risk indicators, including the atherogenic index of plasma, lipid accumulation product, homeostatic model assessment of insulin resistance, and the low-grade inflammation markers, namely, interleukin 6 and high-sensitivity C-reactive protein. Study Design: Cross-sectional study. Methods: We recruited 93 non-obese, healthy young adults. Anthropometric, lipid profile, inflammatory markers, and adipokines were measured. An abnormal adipokine profile (high leptin-to-adiponectin ratio) was considered as a marker of a dysfunctional adipose tissue. The correlation between the leptin-to-adiponectin ratio and the anthropometric measurements, atherogenic index of plasma, lipid accumulation product, homeostatic model assessment of insulin resistance, interleukin 6, and high-sensitivity C-reactive protein was determined. Results: We found a direct correlation between the abnormal adipokine profile and the cardiometabolic risk indicators mentioned above, except for the low-grade inflammatory markers. In the regression model derived from our data, the leptin-to-adiponectin ratio was best correlated with the unfavorable plasma lipid profile, as estimated by the atherogenic index of plasma (r=0.097, confidence interval=0.015-0.180, p=0.021). A significantly higher leptin-to-adiponectin ratio was found in the insulin-resistant group (p=0.012) and in the highest lipid accumulation product quartile (p=0.032). Conclusion: In a non-obese young population, the high rate of leptin-adiponectin may be a good predictor of cardiovascular and metabolic risk assessment.

Adipose tissue and body composition in women six years after gestational diabetes: factors associated with development of type 2 diabetes.

Factors differentiating women at highest risk of progression to type 2 diabetes mellitus (T2DM) after gestational diabetes mellitus (GDM) are incompletely known. Our aim was to characterize adipose tissue and body composition in relation to glucose metabolism in women with a history of GDM and to identify factors associated with development of T2DM. We examined glucose tolerance (OGTT), insulin sensitivity (HOMA-IR), body composition (anthropometry, air displacement plethysmography), and blood chemistry in 39 women 6 years after GDM. An adipose tissue biopsy was obtained to assess the size, number, and lipolytic activity of adipocytes, and adipokine release and density of immune cells and blood vessels in adipose tissue. Normal glucose tolerance (NGT) was identified in 31 women and impaired glucose metabolism (IGM) in 8. Women with IGM had higher BMI/fat mass, and related expected adipose tissue features, than women with NGT. Ethnicity was similar in the groups, but numerically there was a higher proportion of European women in the NGT group and a higher proportion of non-European women in the IGM group. BMI was the best discriminator of NGT versus IGM (multivariable logistic regression: OR = 1.34, P < 0.01). Waist-to-height ratio and adipocyte volume were most strongly associated with HOMA-IR (multivariable linear regression: R2 = 0.656, P < 0.001). After adjustment for BMI/ethnicity, women with IGM had increased serum adipocyte fatty acid-binding protein, weight gain after index pregnancy, and a lower proportion of fat-free mass. These factors, together with high BMI, abdominal fat distribution, and enlarged adipocytes, may increase the risk of progression to T2DM after GDM.

Comparative Secretome Analyses of Primary Murine White and Brown Adipocytes Reveal Novel Adipokines.

The adipose organ, including white and brown adipose tissues, is an important player in systemic energy homeostasis, storing excess energy in form of lipids while releasing energy upon various energy demands. Recent studies have demonstrated that white and brown adipocytes also function as endocrine cells and regulate systemic metabolism by secreting factors that act locally and systemically. However, a comparative proteomic analysis of secreted factors from white and brown adipocytes and their responsiveness to adrenergic stimulation has not been reported yet. Therefore, we studied and compared the secretome of white and brown adipocytes, with and without norepinephrine (NE) stimulation. Our results reveal that carbohydrate-metabolism-regulating proteins are preferably secreted from white adipocytes, while brown adipocytes predominantly secrete a large variety of proteins. Upon NE stimulation, an increased secretion of known adipokines is favored by white adipocytes while brown adipocytes secreted higher amounts of novel adipokines. Furthermore, the secretory response between NE-stimulated and basal state was multifaceted addressing lipid and glucose metabolism, adipogenesis, and antioxidative reactions. Intriguingly, NE stimulation drastically changed the secretome in brown adipocytes. In conclusion, our study provides a comprehensive catalogue of novel adipokine candidates secreted from white and brown adipocytes with many of them responsive to NE. Given the beneficial effects of brown adipose tissue activation on its endocrine function and systemic metabolism, this study provides an archive of novel batokine candidates and biomarkers for activated brown adipose tissue.

Classic and Novel Adipocytokines at the Intersection of Obesity and Cancer: Diagnostic and Therapeutic Strategies.

PURPOSE OF REVIEW: In this review, we investigate the role of classic and novel adipocytokines in cancer pathogenesis synopsizing the mechanisms underlying the association between adipocytokines and malignancy. Special emphasis is given on novel adipocytokines as new evidence is emerging regarding their entanglement in neoplastic development. RECENT FINDINGS: Recent data have emphasized the role of the triad of overweight/obesity, insulin resistance and adipocytokines in cancer. In the setting of obesity, classic and novel adipocytokines present independent and joint effects on activation of major intracellular signaling pathways implicated in cell proliferation, expansion, survival, adhesion, invasion, and metastasis. Until now, more than 15 adipocytokines have been associated with cancer, and this list continues to expand. While the plethora of circulating pro-inflammatory adipocytokines, such as leptin, resistin, extracellular nicotinamide phosphoribosyl transferase, and chemerin are elevated in malignancies, some adipocytokines such as adiponectin and omentin-1 are generally decreased in cancers and are considered protective against carcinogenesis. Elucidating the intertwining of inflammation, cellular bioenergetics, and adiposopathy is significant for the development of preventive, diagnostic, and therapeutic strategies against cancer. Novel more effective and safe adipocytokine-centered therapeutic interventions may pave the way for targeted oncotherapy.

Adipokine Profile in Patients with Type 2 Diabetes Depends on Degree of Obesity.

BACKGROUND The fast pace of life, promoting fast food consumption and low physical activity, has resulted in obesity and/or diabetes as being serious social problems. The aim of the present study was to evaluate concentrations of selected adipokines (leptin, adiponectin, resistin, and visfatin) and to assess the leptin/adiponectin ratio in plasma of type 2 diabetes (T2D) patients in relation to degree of obesity. MATERIAL AND METHODS The study comprised 92 T2D subjects divided into 4 groups according to BMI value - I (normal body weight), II (overweight), III (obesity), and IV (severe obesity) - and 20 healthy volunteers (control group). Each group was divided into male and female subgroups. Plasma concentrations of adipokines were determined by enzyme-linked immunosorbent assay. RESULTS In women, leptin concentration was significantly higher in group IV, whereas in men it was higher in groups III and IV than in the control group and groups I and II. Irrespective of sex, a significant decrease in adiponectin level was observed in group III vs. CONTROL: There was no significant difference in resistin levels. In women visfatin was markedly enhanced in group III, whereas in men in groups II, III and IV vs. CONTROL: Leptin/adiponectin ratio was increased in groups III and IV vs. control in women, whereas in men vs. both control and group I. CONCLUSIONS The obese type 2 diabetic patients presented a disturbed adipokine profile, which seems to be an important link between obesity and T2D. The future studies concerning the question if regulating of adipokines' concentrations could be a promising approach for managing metabolic disorders seem to be well-grounded.

Infrapatellar fat pad features in osteoarthritis: a histopathological and molecular study.

Objective: The infrapatellar fat pad (IFP) is considered a local producer of adipocytokines, suggesting a potential role in OA. The objective of this study was to evaluate the histopathological and molecular characteristics of OA IFPs compared with controls. Methods: The histopathological characteristics of IFPs were evaluated in patients undergoing total knee replacements and in control patients (without OA), considering the following parameters: presence of inflammatory cells, vascularization, adipose lobules dimension and thickness of the interlobular septa. Immunohistochemistry was performed to evaluate VEGF, monocyte chemotactic protein 1 (MCP-1) and IL-6 proteins. Quantitative real time PCR was performed to evaluate the expression levels of adipocytokines in the OA IFPs. Results: OA IFPs showed an increase in inflammatory infiltration, vascularization and thickness of the interlobular septa compared with controls. VEGF, MCP-1 and IL-6 proteins were higher in OA IFPs compared with in controls. Inflammatory infiltration, hyperplasia, vascularization and fibrosis were increased in OA IFP synovial membranes compared with in those of controls. VEGF protein levels were associated with an increased number of vessels in the OA IFPs, while MCP-1 and IL-6 protein levels were associated with higher grades of inflammatory infiltration. Leptin levels were positively correlated with adiponectin and MCP-1expression, while adiponectin positively correlated with peroxisome proliferative activated receptor gamma, MCP-1 and IFP vascularity. MCP-1 showed a positive correlation with peroxisome proliferative activated receptor gamma. IFP lobules dimensions were positively correlated with IL-6 expression and negatively with thickness of interlobular septa. VEGF mRNA levels were positively correlated with increased synovial vascularity. Conclusions: OA IFPs and synovial membranes are more inflamed, vascularized and fibrous compared with those of control patients (without OA).

Relation of antioxidant capacity of diet and markers of oxidative status with C-reactive protein and adipocytokines: a prospective study.

BACKGROUND: The role of dietary antioxidants and plasma oxidant-antioxidant status in low-grade chronic inflammation and adipocytokine levels is not established yet. OBJECTIVES: We aimed to evaluate whether total dietary antioxidant capacity (assessed by dietary ferric reducing antioxidant potential (FRAP)), serum uric acid (UA) and gamma glutamyltransferase (GGT) were associated with low-grade chronic inflammation and circulating adipocytokines. METHODS: Data of 4506 participants aged ≥55years from the Rotterdam Study were analyzed. Baseline (1990-1993) FRAP score was assessed by a food frequency questionnaire. Baseline UA and GGT levels were assessed in non-fasting serum samples. Serum high sensitivity C-reactive protein (hs-CRP) was measured at baseline and 10years later. Plasma leptin, adiponectin, plasminogen activator inhibitor-1 (PAI-1) and resistin levels were assessed 10years later. RESULTS: A high FRAP score was associated with lower levels of UA and GGT. Overall, no association was found between FRAP and hs-CRP levels. FRAP score was associated with lower levels of leptin and PAI-1, higher levels of adiponectin, and no difference in resistin levels. Increased levels of UA were associated with higher levels of hs-CRP, PAI-1 and leptin; lower levels of adiponectin and no difference in resistin levels. Similarly, GGT was associated with higher levels of hs-CRP whereas no association was observed between GGT and adipocytokines. CONCLUSION: These findings suggest that overall antioxidant capacity of diet and low levels of UA are associated with circulating adipocytokines whereas no consistent association was found with hs-CRP.

Synovial fluid adipokines are associated with clinical severity in knee osteoarthritis: a cross-sectional study in female patients with joint effusion.

BACKGROUND: Adipokines are related to knee osteoarthritis, but their exact role is not well known. The aim of this study was to evaluate the association between adipokines in synovial fluid and clinical severity in patients with knee osteoarthritis with joint effusion. METHODS: Cross-sectional study with systematic inclusion of female patients with symptomatic primary knee osteoarthritis with ultrasound-confirmed joint effusion. Age, physical exercise, knee osteoarthritis symptoms duration, classical cardiovascular risk factors and different anthropometric measurements were collected. Metabolic syndrome was defined in accordance to National Cholesterol Education Program-Adult Treatment Panel III. Radiographic severity was evaluated according to Kellgren-Lawrence scale and Lequesne index was used to assess clinical severity. Seven adipokines (leptin, adiponectin, resistin, visfatin, osteopontin, omentin and chemerin) and three inflammatory markers (tumor necrosis factor α, interleukin 6 and high sensitivity C-reactive protein) were measured by enzyme-linked immunosorbent assay in synovial fluid. RESULTS: Kellgren-Lawrence grade, physical exercise, all anthropometric measurements (especially waist circumference), tumor necrosis factor α, and high levels of leptin, resistin, and ostepontin were related to knee osteoarthritis severity. After adjustment for clinical confounders (age, symptom duration, and radiology), anthropometric measurements, inflammatory markers, and all evaluated adipokines, there were independent associations with clinical severity for resistin (directly associated) and visfatin (inversely associated). No other adipokines or inflammatory markers were independently associated with Lequesne index. The association of radiological parameters, physical exercise, and waist circumference with Lequesne index remained after adjustment. CONCLUSIONS: Resistin was directly associated, and visfatin was inversely associated, with clinical severity in female patients with knee osteoarthritis with joint effusion. These associations were more important after adjustment for confounders, especially when all adipokines were evaluated.

Maternal bisphenol A alters fetal endocrine system: Thyroid adipokine dysfunction.

Because bisphenol A (BPA) has been detected in animals, the aim of this study was to investigate the possible effects of maternal BPA exposure on the fetal endocrine system (thyroid-adipokine axis). BPA (20 or 40 µg/kg body weight) was orally administered to pregnant rats from gestation day (GD) 1-20. In both treated groups, the dams and their fetuses had lower serum thyroxine (T4) and triiodothyronine (T3) levels, and higher thyrotropin (TSH) level than control dams and fetuses at GD 20. Some histopathological changes in fetal thyroid glands were observed in both maternal BPA groups at embryonic day (ED) 20, including fibroblast proliferation, hyperplasia, luminal obliteration, oedema, and degeneration. These disorders resulted in the suppression of fetal serum growth hormone (GH), insulin growth factor-1 (IGF1) and adiponectin (ADP) levels, and the elevation of fetal serum leptin, insulin and tumor necrosis factor-alpha (TNFα) levels in both treated groups with respect to control. The depraved effects of both treated groups were associated with reduced maternal and fetal body weight compared to the control group. These alterations were dose dependent. Thus, BPA might penetrate the placental barrier and perturb the fetal thyroid adipokine axis to influence fat metabolism and the endocrine system.

Loss of visceral adipose tissue precedes subcutaneous adipose tissue and associates with n-6 fatty acid content.

BACKGROUND & AIM: During cancer development, fat loss occurs in most cancer patients. Characterization of the behavior of fat loss from visceral (VAT) and subcutaneous adipose tissue (SAT) depots has not been established. The first objective of this study was to assess the intensity and time course of changes in VAT and SAT depots of advanced cancer patients in the year preceding death. Secondly, this study explored the differences in adipokine content and fatty acid composition between VAT and SAT depots and in relation to changes in fat mass. METHODS: Longitudinal quantitative analyses of computed tomography images was conducted to define changes in adipose tissue cross sectional areas in fat depots in advanced colorectal and cholangiocarcinoma cancer patients (n = 46) at mean time points corresponding to 9, 6, 3 and 1 month before death. Proportions of adipose tissue fatty acid and adipokine content were characterized in a second cohort of advanced colorectal cancer patients (n = 16). RESULTS: On average, loss of total adipose tissue (TAT) happens at all time intervals but there is an elevation in the intensity of loss close to death. Nine months from death, 42% of patients were losing fat (Mean TAT cross sectional area change = -0.2 ± 13 cm2) whereas within one month from death, fat wasting was observed in 78% of patients (-60.1 ± 9.2 cm2, P = 0.001). However, loss of TAT did not reflect changes in VAT and SAT in the same direction or intensity. Intensity of VAT loss remains constant throughout the disease progression whereas SAT is more likely to be gained further way from death. Nine month prior to death, mean change in cross sectional area of VAT was -7.9 ± 6.8 cm2 whereas, mean change in CSA of SAT was 7.4 ± 7.7 cm2 (p = 0.03). One month before death, mean VAT and SAT absolute changes were -24.5 ± 4.9 cm2 and -34.5 ± 5.2 cm2, respectively (p = 0.05). Moreover, fat losing patients had higher proportions of polyunsaturated fatty acids, especially n-6 fatty acids, in VAT compared to patients who were gaining fat (mean = 15.4% in losing group vs. 13.4% in gaining group; p = 0.03). VAT contained more monocyte chemoattractant protein-1 than SAT, whereas leptin levels were higher in SAT. CONCLUSIONS: Further from death, VAT and SAT behave differently whereas close to death, accelerated loss occurs in both depots. These differences are further characterized by differences in fatty acid composition and adipokine levels.