Thomas Ebert

Serum levels of the adipokine visfatin are increased in pre‐eclampsia

Objectiveu2002 Pre‐eclampsia (PE) is a serious cardiovascular complication in pregnancy which shares risk factors with the metabolic syndrome including insulin resistance and obesity. Recently, visfatin was introduced as a novel insulin‐mimetic adipokine which is up‐regulated when weight is gained. In the current study, we investigated visfatin serum levels in pre‐eclamptic patients as compared to healthy gestational age‐matched controls.

Circulating high-molecular-weight adiponectin is upregulated in preeclampsia and is related to insulin sensitivity and renal function

OBJECTIVEnPreeclampsia (PE) is a serious cardiovascular complication in pregnancy which is associated with an increased future metabolic and cardiovascular risk for mother and newborn. Recently, a paradoxical upregulation of the insulin-sensitizing and anti-atherogenic adipokine adiponectin has been shown in PE. Furthermore, high-molecular-weight (HMW) adiponectin has been suggested as the biologically active form of this adipokine.nnnDESIGN AND METHODSnHMW adiponectin and total adiponectin serum concentrations were quantified by ELISA in PE (n=16) patients and pregnant control women without PE (n=20). Furthermore, HMW adiponectin and total adiponectin were correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation.nnnRESULTSnMedian maternal HMW adiponectin and total adiponectin levels were significantly and independently upregulated almost twofold in PE when compared with controls. HMW adiponectin and total adiponectin correlated positively with creatinine and negatively with fasting insulin in univariate and multivariate analyses.nnnCONCLUSIONSnWe show that maternal HMW adiponectin and total adiponectin serum concentrations are significantly increased in PE and are positively associated with markers of insulin sensitivity and renal dysfunction. Adiponectin might be part of a physiological feedback mechanism improving insulin sensitivity and cardiovascular health in PE.

Serum Levels of the Adipokine Adipocyte Fatty Acid-binding Protein Are Increased in Preeclampsia

BACKGROUNDnPreeclampsia (PE) is a serious complication of pregnancy which is associated with an increased future metabolic and cardiovascular risk for both mother and newborn. Recently, adipocyte fatty acid-binding protein (AFABP) was introduced as a novel adipokine, serum levels of which independently correlate with the development of the metabolic syndrome and cardiovascular disease in humans. In this study, we investigated serum concentrations of the adipokine AFABP in patients with PE as compared to healthy controls of similar gestational age.nnnMETHODSnAFABP serum levels were quantified by enzyme-linked immunosorbent assay (ELISA) in control (n = 20) and PE (n = 16) patients. Furthermore, AFABP was correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation.nnnRESULTSnMean maternal AFABP concentrations were significantly elevated in PE (24.5 +/- 9.7 microg/l) as compared to controls (14.8 +/- 7.1 microg/l). Furthermore, AFABP serum levels correlated positively with age, body mass index (BMI), blood pressure, serum creatinine, free fatty acids (FFAs), leptin, and C-reactive protein (CRP). In multivariate analyses, BMI and serum creatinine remained independently associated with AFABP concentrations and explained 58% of the variation in AFABP levels.nnnCONCLUSIONnWe demonstrate that maternal AFABP serum concentrations are significantly increased in PE. Furthermore, BMI and serum creatinine are independent predictors of circulating AFABP.

Serum levels of irisin in gestational diabetes mellitus during pregnancy and after delivery

OBJECTIVEnIrisin has recently been introduced as a novel an exercise-inducible myokine which improves glucose metabolism in mice. However, regulation of circulating irisin in gestational diabetes mellitus (GDM) and in the peripartal period has not been assessed so far.nnnMETHODSnCirculating irisin was quantified in 74 GDM patients and in 74 healthy, pregnant, gestational age-matched controls. In a subset of these patients (44 GDM, 41 controls), postpartum follow-up data were also available. In a second study population of 40 healthy women with singleton pregnancies undergoing elective Cesarean section, irisin was assessed in maternal serum before and within 24h after delivery, as well as in umbilical cord blood and in placental tissue.nnnRESULTSnIn the first study population, median [interquartile range] irisin levels were significantly higher in GDM patients as compared to controls after delivery (previous GDM: 446.3 [146.9]μg/l; controls: 378.0 [111.4]μg/l) but not during pregnancy (GDM: 482.1 [132.1]μg/l; controls: 466.6 [178.0]μg/l). Interestingly, fasting insulin (FI) was independently and positively associated with serum irisin in multivariate analysis during pregnancy. In agreement with these findings, relative changes (ratio) of FI independently and positively predicted relative changes of irisin (ratio) in the second study population.nnnCONCLUSIONSnThe myokine irisin is independently associated with FI in pregnancy. The physiological significance of these findings needs to be assessed in future experiments.

Serum levels of fibroblast growth factor-21 are increased in chronic and acute renal dysfunction

Fibroblast growth factor (FGF)‐21 has recently been introduced as a circulating adipokine which reverses insulin resistance and obesity in rodents. In this study, regulation of FGF‐21 in renal dysfunction was elucidated in both chronic kidney disease (CKD) and acute kidney dysfunction (AKD).

Circulating Angiopoietin-like Protein 8 Is Independently Associated With Fasting Plasma Glucose and Type 2 Diabetes Mellitus

OBJECTIVEnAngiopoietin-like protein 8 (Angptl8) has recently been introduced as a novel adipokine/hepatokine that promotes pancreatic β-cell proliferation and improves glucose tolerance in mouse models of insulin resistance. However, regulation of Angptl8 in human type 2 diabetes mellitus (T2DM) and renal dysfunction has not been determined.nnnRESEARCH DESIGN AND METHODSnSerum Angptl8 levels were quantified by ELISA in 62 patients with T2DM as compared with 58 nondiabetic subjects in vivo. Within both groups, about half of the patients were on chronic hemodialysis or had an estimated glomerular filtration rate above 50 mL/min/1.73 m(2). Furthermore, we investigated the effect of insulin and differentiation on Angptl8 mRNA expression in 3T3-L1 adipocytes in vitro.nnnRESULTSnMedian [interquartile range] serum Angptl8 levels were higher in patients with T2DM (1.19 [0.37] μg/L) as compared with nondiabetic subjects (1.03 [0.47] μg/L) (P = .005). Furthermore, the adipokine/hepatokine was significantly higher in women (1.21 [0.47] μg/L) as compared with men (1.05 [0.44] μg/L]) (P = .013). In multivariate analysis, fasting glucose and T2DM but not renal function remained independent and positive predictors of circulating Angptl8 even after adjustment for markers of obesity, lipid status, and inflammation (P < .05). Furthermore, Angptl8 mRNA expression was induced by insulin and during adipogenesis in 3T3-L1 adipocytes in vitro.nnnCONCLUSIONSnCirculating Angptl8 is positively and independently associated with T2DM and fasting glucose in vivo. Furthermore, Angptl8 mRNA expression is induced by insulin and during adipogenesis in 3T3-L1 adipocytes in vitro.

Serum Levels of the Adipokine Progranulin Depend on Renal Function

OBJECTIVE Progranulin has recently been introduced as a novel adipokine inducing insulin resistance and obesity. In the current study, we investigated renal elimination, as well as association of the adipokine with markers of the metabolic syndrome. RESEARCH DESIGN AND METHODS Progranulin serum levels were quantified by enzyme-linked immunosorbent assay and correlated to anthropometric and biochemical parameters of renal function and glucose and lipid metabolism, as well as inflammation, in 532 patients with stages 1–5 of chronic kidney disease (CKD). RESULTS Median serum progranulin levels adjusted for age, sex, and BMI were significantly different between CKD stages with highest values detectable in stage 5 (stage 1, 58.3 µg/L; stage 2, 63.0 µg/L; stage 3, 65.4 µg/L; stage 4, 68.8 µg/L; and stage 5, 90.6 µg/L). Furthermore, CKD stage was the strongest independent predictor of circulating progranulin in our cohort. In addition, high-sensitivity interleukin-6 and adiponectin remained significantly and independently correlated with the adipokine. CONCLUSIONS We demonstrate that progranulin serum levels increase with deteriorating renal function. These findings are in accordance with the hypothesis that renal clearance is a major elimination route for circulating progranulin. Furthermore, the adipokine is positively and independently associated with markers of inflammation and adiponectin.

Serum levels of angiopoietin-related growth factor in diabetes mellitus and chronic hemodialysis

Angiopoietin-related growth factor (AGF) was recently introduced as a novel liver-derived protein that antagonizes obesity and insulin resistance. In the current study, we investigated circulating AGF levels in relation to renal function and type 2 diabetes mellitus (T2DM). Angiopoietin-related growth factor was determined by enzyme-linked immunosorbent assay in subjects with a glomerular filtration rate greater than 50 mL/min (n = 60, 30 diabetic and 30 nondiabetic) and in patients on chronic hemodialysis (CD; n = 60, 32 diabetic and 28 nondiabetic). Furthermore, AGF was correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, as well as inflammation. Median serum AGF levels were significantly lower in CD patients (125.9 +/- 96.3 microg/L) as compared with subjects with a glomerular filtration rate greater than 50 mL/min (164.0 +/- 95.4 microg/L) (P < .05). Furthermore, AGF serum levels were significantly increased in diabetic patients (161.7 +/- 114.2 microg/L) as compared with nondiabetic subjects (123.0 +/- 88.2 microg/L) (P < .01). Moreover, CD negatively and T2DM positively predicted AGF concentrations in multiple regression analysis. In addition, fasting serum glucose was independently and positively correlated with circulating AGF in all patients and controls. Our results suggest that renal dysfunction is negatively and T2DM is positively associated with AGF serum levels. Further studies are needed to better elucidate the physiologic significance of circulating AGF in human disease.

Circulating adipocyte fatty acid-binding protein induces insulin resistance in mice in vivo

Circulating levels of the adipokine adipocyte fatty acid‐binding protein (AFABP) are increased in obesity. However, the influence of circulating AFABP on insulin sensitivity in vivo remains unclear.

Leptin dose-dependently decreases atherosclerosis by attenuation of hypercholesterolemia and induction of adiponectin.

OBJECTIVESnConflicting evidence concerning leptin in atherosclerosis has been published. Furthermore, dose-dependent effects of leptin on atherogenesis have not been studied.nnnMETHODSnLeptin-deficient low-density lipoprotein receptor (LDLR) knockout (LDLR(-/-);ob/ob) mice were treated with saline, 0.1, 0.5, or 3.0mg/kg body weight (BW)/d recombinant leptin over 12weeks starting at 8weeks of age. Aortic root and brachiocephalic artery (BCA) atherosclerotic lesions were analyzed by oil red O staining. Furthermore, glucose homeostasis, lipid metabolism, and liver function including tissue studies were assessed in all animals.nnnRESULTSnLeptin treatment dose-dependently decreased BW in LDLR(-/-);ob/ob mice as compared to saline. Mice in the 0.1 and 0.5mg/kgBW/d groups remained heavier (i.e. subphysiological leptin dose) and in the 3.0mg/kgBW/d group had similar weight (i.e. physiological leptin dose) as compared to non-leptin-deficient LDLR(-/-) animals. Recombinant leptin dose-dependently reduced plaque area in the aortic root and the BCA by 36% and 58%, respectively. Leptin-mediated reductions of plasma total and LDL-cholesterol (Chol) remained independent predictors for aortic root plaque area. Chol content in liver, as well as hepatic expression of key lipid and proinflammatory genes, were dose-dependently regulated by leptin. Furthermore, leptin treatment increased circulating levels and adipose tissue mRNA expression of the adipokine adiponectin.nnnCONCLUSIONSnLeptin administration within the subphysiological to physiological range diminishes atherosclerotic lesions. Leptin appears to mediate its antiatherogenic effects indirectly through reduction of hypercholesterolemia and liver steatosis, as well as upregulation of insulin-sensitizing and atheroprotective adiponectin.