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Vaspin levels are significantly higher in women, and gender is an independent predictor of circulating vaspin in both control and CD patients. In addition, age independently predicts vaspin in control patients, whereas GFR and CRP are independently associated with this adipokine in CD patients. In contrast, circulating vaspin is not independently associated with markers of glucose and lipid metabolism.

Recently, visfatin was characterized as a novel adipocytokine that is upregulated in obesity and exerts insulinmimetic effects in various tissues. To clarify expression and regulation of this adipocytokine, visfatin mRNA was measured by quantitative real-time reverse transcriptionpolymerase chain reaction in 3T3-L1 adipocytes during adipogenesis and after treatment with various hormones known to alter insulin sensitivity. Visfatin expression was about 6-fold higher in 3T3-L1 adipocytes in vitro as compared with epididymal fat in vivo and increased during adipogenic conversion more than 3-fold. Interestingly, 100 nM dexamethasone significantly increased visfatin mRNA by almost 1·5-fold. In contrast, 500 ng/ml growth hormone (GH), 10 ng/ml tumor necrosis factor (TNF) , and 10 µM isoproterenol downregulated visfatin expression by 45%, 36%, and 43% respectively. Insulin did not influence synthesis of this adipocytokine. The effects of dexamethasone, GH, TNF and isoproterenol were time-and dose-dependent. Furthermore, activation of G s -protein-coupled pathways by forskolin and cholera toxin was sufficient to significantly downregulate visfatin mRNA. Taken together, our results show a differential regulation of visfatin mRNA by insulin resistanceinducing hormones, supporting the view that this adipocytokine might be an interesting novel candidate linking core components of the metabolic syndrome such as obesity and insulin resistance.

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Visfatin is a novel adipocytokine exerting insulin-mimetic effects in various insulin-sensitive tissues such as liver, muscle, and fat. In contrast, interleukin (IL)-6 is a proinflammatory adipose-secreted factor that induces insulin resistance and plasma concentrations that correlate with the development of type 2 diabetes mellitus. In the present study, the impact of IL-6 on visfatin gene expression in 3T3-L1 adipocytes was determined by quantitative real-time reverse transcription-polymerase chain reaction. Interestingly, 30 ng/ml IL-6 time-dependently downregulated visfatin synthesis with a significant 40% suppression seen after 4 h of treatment. Furthermore, the addition of IL-6 for 16 h dose-dependently suppressed visfatin mRNA with significant effects first observed at concentrations as low as 3 ng/ml and a maximal 43% reduction at 30 ng/ml effector. Moreover, inhibitor studies suggested that the negative effect of IL-6 on visfatin expression is, at least in part, mediated by p44/42 mitogen-activated protein kinase. In contrast, troglitazone did not reverse the negative effect of IL-6 on visfatin synthesis under these conditions. Taken together, our study suggests that IL-6 might influence glucose tolerance in part by regulation of the novel insulin-mimetic adipocytokine visfatin.

Objective: Irisin has recently been introduced as a novel myokine which reverses visceral obesity and improves glucose metabolism in mice. However, regulation of irisin in humans in relation to renal and metabolic disease has not been comprehensively studied. Design and methods: Serum irisin levels were quantified by ELISA and correlated with anthropometric and biochemical parameters of renal function, glucose and lipid metabolism, as well as inflammation, in 532 patients with stages 1-5 of chronic kidney disease (CKD). Results: Median serum irisin levels adjusted for age, gender, and BMI significantly decreased with increasing CKD stage and lowest concentrations were seen in patients with CKD stage 5. Furthermore, irisin concentrations were associated with facets of the metabolic syndrome including diastolic blood pressure, markers of impaired glucose tolerance, and dyslipidemia in univariate analysis. Moreover, markers of renal function, e.g. glomerular filtration rate, and insulin resistance, e.g. homeostasis model assessment of insulin resistance, remained independently associated with circulating irisin levels in robust multivariate analysis. Conclusions: We show that irisin serum concentrations decrease with increasing CKD stage and are independently and positively predicted by renal function and insulin resistance. The physiological relevance of our findings, as well as the factors contributing to irisin regulation in humans, needs to be further defined in future experiments.

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OBJECTIVE -To investigate renal elimination of the adipokine fibroblast growth factor 21 (FGF21) by determining circulating FGF21 levels in patients on chronic hemodialysis (CD) as compared with control subjects with a glomerular filtration rate (GFR) Ͼ50 ml/min.RESEARCH DESIGN AND METHODS -FGF21 was determined by enzyme-linked immunosorbent assay in control (n ϭ 60) and CD (n ϭ 60) patients and correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, and inflammation in both groups.RESULTS -Median serum FGF21 levels were Ͼ15-fold higher in CD patients (3,710.6 ng/l) than in subjects with a GFR Ͼ50 ml/min (201.9 ng/l) (P Ͻ 0.001). Furthermore, serum creatinine positively and GFR negatively predicted FGF21 concentrations in multiple regression analyses in control subjects (P Ͻ 0.05).CONCLUSIONS -FGF21 serum levels increase in CD patients and are related to markers of renal function in control subjects. Diabetes Care 32:126-128, 2009R ecently, fibroblast growth factor 21 (FGF21) was introduced as a novel adipokine with potent antidiabetic properties (1-4). In contrast to extensive experiments in animals, only one study to date has determined regulation and function of FGF21 in humans in vivo (5), and no data have been published about the relation of this adipokine to renal function. RESEARCH DESIGN AND METHODS -The design of the study has been described in detail recently (6 -8). Briefly, 120 Caucasian men (n ϭ 62) and women (n ϭ 58) were recruited with 60 patients having a glomerular filtration rate (GFR) Ͼ50 ml/min (control subjects) as assessed by the original Modification of Diet in Renal Disease formula (9) and 60 patients being on chronic hemodialysis (CD). A total of 30 control subjects and 32 CD patients had type 2 diabetes. The study was approved by the local ethics committee, and all subjects gave written informed consent before taking part in the study. AssaysBlood samples were taken after an overnight fast. In CD patients, blood was drawn just before hemodialysis started. FGF21 (Biovendor, Modrice, Czech Republic), adiponectin (Mediagnost, Reutlingen, Germany), and leptin (Mediagnost) were determined with enzyme-linked immunosorbent assays according to the manufacturer's instructions. Statistical analysisStatistical analyses are specified in RESULTS and in the Table 1 legend. Table 1 summarizes clinical characteristics of the subgroups studied (control, CD) further divided into nondiabetic and diabetic subjects. Median circulating FGF21 was Ͼ15-fold higher in CD patients (3,710.6 Ϯ 5,541.3 ng/l) compared with control subjects (201.9 Ϯ 275.5 ng/l) (P Ͻ 0.001) ( Table 1). Furthermore, FGF21 serum levels were significantly higher in men (1,959.0 Ϯ 4,505.5 ng/l) compared with women (446.9 Ϯ 1,609.0 ng/l) (P Ͻ 0.05) but did not depend on type 2 diabetes. RESULTS FGF21 serum levels are increased in CD patients Univariate correlationsUsing the Spearman's rank correlation method, serum FGF21 concentrations positively correlated with BMI (r ϭ 0.33, 95% CI 0.08 -0.54, P ϭ ...