Association between TGFß1 Levels in Cord Blood and Weight Progress in the First Year of Life.

Transforming growth factor beta-1 (TGFß1) is an adipokine secreted from adipose tissue, placental tissue and immune cells with a role in cell proliferation, cell apoptosis and angiogenic proliferation. The role of TGFß1 in pregnancy and child growth and the source of cord TGFß1 are yet unknown. In this study, we sought to clarify the correlation of TGFß1 levels with parameters of intrauterine growth and child growth during the first year of life, and to determine whether their source is primarily of fetal or maternal origin. Serum samples and anthropometric measurements were obtained from the LIFE Child cohort of 79 healthy mother-child pairs. Measurements were conducted using enzyme-linked immunosorbent assays. Statistical analyses including Mann-Whitney U-test, correlation analyses and linear regression analyses were performed using GraphPad Prism and R. TGFß1 levels were significantly higher in cord than in maternal serum, suggesting a fetal origin. Multivariate regression analyses revealed strong positive associations between cord TGFß1 levels at birth and child weight at U6. Furthermore, cord TGFß1 was significantly correlated with child weight at approximately one year of age. An increase of 10,000 pg/mL in cord TGFß1 concentrations at birth was associated with a higher body weight of 201 g at roughly one year of age when adjusted for sex.

Leptin Improves Parameters of Brown Adipose Tissue Thermogenesis in Lipodystrophic Mice.

Lipodystrophy syndromes (LD) are a heterogeneous group of very rare congenital or acquired disorders characterized by a generalized or partial lack of adipose tissue. They are strongly associated with severe metabolic dysfunction due to ectopic fat accumulation in the liver and other organs and the dysregulation of several key adipokines, including leptin. Treatment with leptin or its analogues is therefore sufficient to reverse some of the metabolic symptoms of LD in patients and in mouse models through distinct mechanisms. Brown adipose tissue (BAT) thermogenesis has emerged as an important regulator of systemic metabolism in rodents and in humans, but it is poorly understood how leptin impacts BAT in LD. Here, we show in transgenic C57Bl/6 mice overexpressing sterol regulatory element-binding protein 1c in adipose tissue (Tg (aP2-nSREBP1c)), an established model of congenital LD, that daily subcutaneous administration of 3 mg/kg leptin for 6 to 8 weeks increases body temperature without affecting food intake or body weight. This is associated with increased protein expression of the thermogenic molecule uncoupling protein 1 (UCP1) and the sympathetic nerve marker tyrosine hydroxylase (TH) in BAT. These findings suggest that leptin treatment in LD stimulates BAT thermogenesis through sympathetic nerves, which might contribute to some of its metabolic benefits by providing a healthy reservoir for excess circulating nutrients.

Adipocyte Fatty Acid-Binding Protein 4 is Altered in Growth Discordant Dichorionic, but not in Monochorionic Twins.

CONTEXT: The fetal period has a critical and long-lasting impact on the regulation of metabolic processes and a life-long predisposition for obesity and metabolic syndrome. The exact mechanisms are unknown, but epigenetic regulation likely plays a major role. Twins represent an excellent model to study these mechanisms, as they share the same intrauterine environment and similar or even the same genetic information. We examined cord blood levels of adipocyte fatty-acid binding protein 4 (A-FABP or FABP4), a novel adipokine correlated with obesity and metabolic disease in children and adults. OBJECTIVE: To examine A-FABP levels in the cord blood of twins with concordant and discordant growth and in singletons with intrauterine growth restriction (IUGR). DESIGN: Cohort study of 36 twin pairs (25 growth concordant and 11 growth discordant), and 42 singleton pregnancies (28 IUGR and 13 normally grown controls, 1 HELLP). OUTCOME MEASURES: Cord blood A-FABP levels measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: A-FABP levels were higher in the smaller of growth discordant dichorionic (DC) twins versus their co-twins (109.46 ±â€…62.80 ng/mL vs. 72.93 ±â€…36.66 ng/mL, P = 0.028). A-FABP was negatively correlated with birth weight and gestational age (P < 0.001), but not with birth weight z-score (P = 0.37). CONCLUSIONS: Increased A-FABP levels might be associated with an increased metabolic risk in growth-restricted (twins) and prematurely born infants.

Leptin decreases circulating inflammatory IL-6 and MCP-1 in mice.

Leptin influences inflammation and immune response. Dose-dependent effects of leptin on biomarkers of inflammation have not been studied in vivo, so far. Leptin-deficient low-density lipoprotein receptor (LDLR) knockout (LDLR-/- ;ob/ob) female mice were treated with three different leptin doses or saline for 12 weeks. The effect of leptin on plasma interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 concentrations and Il-6 and Mcp-1 mRNA expression in vivo were assessed. Macrophage infiltration in epididymal adipose tissue (epiAT) after leptin treatment was determined by quantitative immunohistochemical analysis. Aortic root atherosclerotic lesions were analyzed by oil red O staining. Mean plasma IL-6 and MCP-1 decreased significantly in the 3.0 mg/kg BW/day group as compared to control mice (both P < 0.01). Messenger RNA expression of Il-6 and Mcp-1 was significantly down-regulated by leptin treatment in different adipose tissues in vivo. Characteristic crown-like structures formed by adipose tissue macrophages were significantly reduced by leptin treatment in epiAT. Recombinant leptin dose-dependently diminished plaque area in the aortic root. Leptin administration within the subphysiological to physiological range diminishes circulating pro-inflammatory IL-6 and MCP-1. Reduction of Il-6 and Mcp-1 gene expression in adipose tissue, as well as decreased adipose tissue macrophage infiltration might contribute. © 2018 BioFactors, 45(1):43-48, 2019.

Leptin restores markers of female fertility in lipodystrophy.

OBJECTIVES: Female reproductive dysfunction occurs in patients with pathological loss of adipose tissue, i.e. lipodystrophy (LD). However, mechanisms remain largely unclear and treatment effects of adipocyte-derived leptin have not been assessed in LD animals. METHODS: In the current study, C57Bl/6 LD mice on a low-density lipoprotein receptor knockout background were treated with leptin or saline for 8 weeks and compared to non-LD controls. RESULTS: The number of pups born was 37% lower in breeding pairs consisting of LD female mice x non-LD male mice (n = 3.3) compared to LD male mice x non-LD female mice (n = 5.2) (p < 0.05). Mean uterus weight was significantly lower in the saline-treated LD group (18.8 mg) compared to non-LD controls (52.9 mg; p < 0.0001) and increased significantly upon leptin treatment (46.5 mg; p < 0.001). The mean number of corpora lutea per ovary was significantly lower in saline-treated LD animals compared to non-LD controls (p < 0.01) and was restored to non-LD control levels by leptin (p < 0.05). Mechanistically, mRNA expression of ovarian follicle-stimulating hormone receptor (p < 0.01) and estrogen receptor ß (p < 0.05), as well as of pituitary luteinizing hormone ß subunit (p < 0.001) and follicle-stimulating hormone ß subunit (p < 0.05), was significantly upregulated in LD mice compared to non-LD controls. In addition, mean time to vaginal opening as a marker of puberty onset was delayed by 12.5 days in LD mice (50.9 days) compared to non-LD controls (38.4 days; p < 0.001). CONCLUSIONS: Female LD animals show impaired fertility which is restored by leptin. Future studies should assess leptin as a subfertility treatment in human leptin-deficiency disorders.

Regulation of the novel adipokines/ hepatokines fetuin A and fetuin B in gestational diabetes mellitus.

OBJECTIVE: Fetuin B has recently been introduced as a novel adipokine/hepatokine which is significantly increased in hepatic steatosis and mediates impaired insulin action, as well as glucose intolerance. However, regulation of fetuin B in gestational diabetes mellitus (GDM), as well as its longitudinal changes in the peripartum period, have not been elucidated, so far. DESIGN AND METHODS: Circulating fetuin A and fetuin B were quantified in 74 women with GDM and 74 healthy and gestational age-matched controls by enzyme-linked immunosorbent assay during pregnancy (median gestational age: 201days). Furthermore, fetuin B was quantified during pregnancy as compared to postpartum levels in a follow-up study (median time after delivery: 4years and 115days). RESULTS: Median [interquartile range] serum fetuin B levels were significantly higher in women with GDM (4.8 [1.7] mg/l) as compared to non-diabetic pregnant controls (4.3 [1.2] mg/l) (p=0.013) during pregnancy. In multivariate analysis, GDM status, insulin resistance, and fetuin A were independent and positive predictors of circulating fetuin B. Furthermore, fetuin B serum concentrations significantly decreased after delivery from 4.6 [1.7] mg/l (prepartum) to 3.0 [2.2] mg/l (postpartum) in all women (p<0.001). CONCLUSIONS: Women with GDM have significantly higher fetuin B levels as compared to healthy pregnant control women and GDM status, insulin resistance, and fetuin A positively predict circulating fetuin B. Postpartum fetuin B is decreased as compared to prepartum values suggesting a placental co-secretion of this novel adipokine/hepatokine. Further studies need to elucidate factors contributing to fetuin B regulation in humans, as well as the pathophysiological significance of fetuin B upregulation in GDM.

Leptin Within the Subphysiological to Physiological Range Dose Dependently Improves Male Reproductive Function in an Obesity Mouse Model.

Obesity has recently been linked with reduced fertility, and the mechanisms underpinning this effect are currently unknown. The adipokine leptin is dysregulated in obesity and affects reproductive tracts; therefore, we investigated the dose-dependent effects of leptin on Leydig cell function and spermatogenesis. Eight-week-old leptin-deficient obese (ob/ob) male mice were treated with subphysiological (0.1- or 0.5-mg/kg body weight [BW]/d) or physiological (3.0-mg/kg BW/d) doses of leptin or saline for 12 weeks (chronic treatment) or 72 hours (acute treatment). We then evaluated male reproductive function markers. Mean testis weight increased significantly in the 0.1- and 3.0-mg/kg BW/d groups compared with saline controls (both P < .05). Intratesticular testosterone levels relative to testis weight significantly increased in the 0.5-mg/kg BW/d group compared with saline controls (P < .05). FSH levels increased in a dose-dependent manner with leptin treatment, whereas LH levels did not change. Leptin treatment significantly up-regulated both mRNA and protein expression of the steroidogenic enzyme cytochrome P450 17A1. Spermatogenesis improved in leptin-treated animals. Significantly more seminiferous tubules were observed in stages I-VIII (P < .01), and there were fewer abnormal seminiferous tubule structures (P < .01). Acute treatment with physiological leptin doses partially improved male reproductive markers without changing BW. Administration of subphysiological to physiological doses of leptin improves Leydig cell function and spermatogenesis.

The adipokine preadipocyte factor-1 is downregulated in preeclampsia and expressed in placenta.

BACKGROUND: Adipokines contribute to the development of preeclampsia (PE), a severe pregnancy complication which increases the future risk for cardiovascular and metabolic disease in both mother and newborn. Pre-adipocyte factor-1 (Pref-1) was recently introduced as a novel antiangiogenic and antiadipogenic adipokine. MATERIAL AND METHODS: Pref-1 was quantified in patients with PE (n=51) and healthy pregnant controls (n=51) during pregnancy, as well as 6 months after delivery (study population 1). Furthermore, Pref-1 was investigated in the immediate peripartal period and the placenta in 40 healthy pregnant women undergoing elective cesarean section (study population 2). RESULTS: In study population 1, median Pref-1 serum concentrations during pregnancy were significantly lower in women with PE (0.5 µg/l) as compared to healthy pregnant controls (0.7 µg/l) (p<0.001). Furthermore, Pref-1 serum concentrations were independently predicted by PE, leptin levels, and gestational age in this population. In both study populations, Pref-1 serum levels significantly decreased after delivery as compared to prepartal levels. Moreover, significant expression of Pref-1 was detected in placental tissue. CONCLUSION: Maternal Pref-1 serum concentrations are significantly decreased in PE. The pathophysiological significance of this regulation needs to be studied in more detail in future experiments.

Betatrophin levels are increased in women with gestational diabetes mellitus compared to healthy pregnant controls.

OBJECTIVE: Betatrophin has recently been introduced as a novel adipokine/hepatokine, which promotes pancreatic ß cell proliferation and improves glucose tolerance in several mouse models of insulin resistance. However, regulation of betatrophin in gestational diabetes mellitus (GDM), as well as its association with markers of obesity, such as glucose and lipid metabolism, inflammation, and renal function, have not been elucidated. DESIGN AND METHODS: Circulating betatrophin was quantified in 74 women with GDM and 74 healthy and gestational age-matched controls by ELISA. In a subset of the study population comprising of 85 patients (41 previous controls, 44 previous women with GDM), postpartum betatrophin levels were measured in a follow-up study. RESULTS: Median (interquartile range) serum betatrophin levels were higher in women with GDM (1.79 (0.53) µg/l) as compared to non-diabetic pregnant controls (1.58 (0.44) µg/l) (P=0.002). In multivariate analysis, GDM status was an independent and positive predictor of circulating betatrophin (P=0.001). Furthermore, betatrophin levels were significantly higher during gestation (1.70 (0.53) µg/l) as compared to postpartum levels (1.55 (0.66) µg/l) (P=0.028). Moreover, postpartum irisin remained a positive and independent predictor of postpartum betatrophin concentrations. CONCLUSIONS: Women with GDM have significantly higher betatrophin levels as compared to healthy pregnant controls and GDM status positively predicts circulating betatrophin. Furthermore, postpartum levels are significantly lower as compared to betatrophin concentrations during pregnancy. Moreover, irisin is a significant predictor of postpartum betatrophin levels.

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

OBJECTIVE: 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. METHODS: C57BL/6NTac mice (10 weeks) were treated over 8 weeks i.p. with saline (control) or recombinant AFABP (0.5 mg/kg/d). A comprehensive characterization of metabolic parameters, body composition, and energy expenditure was performed. Furthermore, the effect of AFABP on pancreatic ß-cell responsiveness, hepatic glycogen content, and peroxisome proliferator-activated receptor (PPAR) γ protein expression was elucidated. RESULTS: In male mice, AFABP treatment induced insulin resistance with significantly increased fasting insulin, C-peptide, and homeostasis model assessment of insulin resistance. In female animals, a similar trend was observed. In both genders, no difference in body weight, lipid parameters, body composition, or energy expenditure could be detected between AFABP-treated and control mice. Insulin resistance in male AFABP-treated mice was accompanied by decreased PPARγ protein content in perigonadal adipose tissue and diminished circulating adiponectin. AFABP treatment did not affect pancreatic ß-cell responsiveness and hepatic glycogen content. CONCLUSIONS: Circulating AFABP induces insulin resistance in male mice. AFABP-mediated degradation of PPARγ in adipose tissue and subsequently decreased expression of insulin-sensitizing adiponectin are potential mechanisms for this effect.

Serum levels of sclerostin in cardiometabolic disorders during pregnancy.

OBJECTIVE: Sclerostin has recently been introduced as a novel osteocyte-secreted factor which is associated with an adverse metabolic profile. However, regulation of circulating sclerostin in cardiometabolic disorders during pregnancy including gestational diabetes mellitus (GDM) and preeclampsia (PE) has not been comprehensively assessed, so far. METHODS: Serum levels of sclerostin were quantified in 72 women with GDM and in 72 healthy, pregnant, gestational age-matched controls (study population 1). Furthermore, circulating sclerostin was assessed in 51 women with PE as compared to 51 pregnant controls in a second cohort (study population 2). RESULTS: In the first study population (GDM), median [interquartile range] sclerostin levels were not significantly different in women with GDM as compared to controls (GDM: 19.2 [8.1]pmol/l; controls: 18.6 [7.1]pmol/l; p=0.906). Interestingly, C reactive protein was a negative and independent predictor of circulating sclerostin in the GDM cohort in multivariate analysis. In study population 2 (PE), serum levels of sclerostin were not different between women with PE and controls (PE: 18.8 [9.2]pmol/l; controls: 19.3 [8.8]pmol/l; p=0.504). Furthermore, the osteocyte-secreted factor was not related to any metabolic and gestational parameter in this cohort. CONCLUSIONS: Sclerostin serum levels are not associated with an adverse metabolic profile during pregnancy in women with GDM and PE. The physiological significance of different associations of circulating sclerostin between pregnancy and non-pregnant status needs to be determined in future experiments.

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

OBJECTIVE: 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). STUDY DESIGN AND METHODS: Serum concentrations of total FGF-21 were quantified by enzyme-linked immunosorbent assay in 499 patients with CKD stages 1-5 (study population 1). Furthermore, total FGF-21 was determined before and within 30 h after unilateral nephrectomy, a model of AKD, in 32 patients (study population 2). FGF-21 levels were correlated to anthropometric and biochemical parameters of renal function, glucose and lipid metabolism, as well as inflammation, in both studies. RESULTS: In study population 1, median [interquartile range] circulating FGF-21 adjusted for age, gender and body mass index was significantly different between CKD stages with highest values detectable in stage 5 (stage 1: 86·4 [132·9]; 2: 206·4 [223·1]; 3: 289·8 [409·3]; 4: 591·3 [789·0]; 5: 1918·1 [4157·0] ng/l). Furthermore, estimated glomerular filtration rate remained a strong independent and negative predictor of FGF-21. In study population 2, FGF-21 increased significantly postsurgically (325·0 [984·0] ng/l) as compared to presurgical values (255·5 [243·0] ng/l). Furthermore, relative changes of FGF-21 were independently and positively predicted by relative changes of creatinine. CONCLUSIONS: We demonstrate that circulating FGF-21 is increased in both CKD and AKD. Our results suggest renal excretion as a major route for FGF-21 elimination. The pathophysiological significance of these findings needs to be elucidated in more detail.

Serum levels of the myokine irisin in relation to metabolic and renal function.

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.

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

OBJECTIVE: Irisin 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. METHODS: Circulating 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. RESULTS: In 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. CONCLUSIONS: The 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 the adipokine fibroblast growth factor-21 are increased in preeclampsia.

BACKGROUND: Preeclampsia (PE) is a serious cardiovascular complication in pregnancy, which is associated with an increased future metabolic and cardiovascular risk for mother and newborn. Fibroblast growth factor (FGF)-21 was recently introduced as a novel adipokine improving glucose metabolism in vitro and in vivo. MATERIAL AND METHODS: We investigated serum FGF-21 levels in patients with PE (n=51) as compared to healthy, age-matched controls (n=51) during and 6 months after pregnancy. Furthermore, association of FGF-21 with markers of renal function, glucose and lipid metabolism, as well as inflammation, was elucidated in all individuals. RESULTS: Median maternal FGF-21 serum concentrations adjusted for body mass index and gestational age at blood sampling were significantly, almost 3-fold increased in PE patients (309.6 ng/l) as compared to healthy, age-matched pregnant women (105.2 ng/l) (p<0.001). Furthermore, FGF-21 concentrations were independently and positively correlated with triglycerides whereas an independent and negative association was observed with glomerular filtration rate and low density lipoprotein (LDL) cholesterol in pregnant women. Moreover, FGF-21 serum levels significantly decreased in former PE patients 6 months after pregnancy approaching levels found in control patients. CONCLUSIONS: Maternal FGF-21 serum concentrations are significantly increased in PE during pregnancy. Furthermore, triglycerides, glomerular filtration rate, and LDL cholesterol are independent predictors of circulating FGF-21 in pregnant women.

Serum levels of growth arrest specific protein 6 are increased in preeclampsia.

Preeclampsia (PE) contributes to maternal and fetal morbidity and mortality worldwide. Moreover, it is associated with an increased future metabolic and cardiovascular risk for mother and newborn. Recently, growth arrest specific protein (Gas) 6 has been introduced as a novel metabolic risk factor with anti-angiogenic, pro-atherogenic, and pro-adipogenic properties. In the current study, we investigated serum concentrations of Gas6 in patients with PE (n=51) as compared to healthy, age-matched controls (n=51) during and 6 months after pregnancy. Furthermore, association of Gas6 with markers of renal function, glucose and lipid metabolism, as well as inflammation, was assessed in all individuals. Median maternal Gas6 serum levels adjusted for body mass index and gestational age at blood sampling were significantly increased in PE patients (5.7 µg/l) as compared to healthy, age-matched pregnant women (4.6 µg/l) (p<0.05). Furthermore, Gas6 concentrations positively correlated with blood pressure, creatinine, free fatty acids, C-reactive protein, leptin, and adiponectin during pregnancy. Moreover, leptin and adiponectin remained independently associated with Gas6 levels in multivariate analysis. Gas6 serum levels 6 months after pregnancy were not significantly different between former PE and control patients. Taken together, maternal Gas6 serum concentrations are significantly increased in PE during pregnancy. Furthermore, the adipokines leptin and adiponectin are independent predictors of circulating Gas6 in pregnant women.

Fibroblast growth factor-21 serum concentrations are associated with metabolic and hepatic markers in humans.

Rather than a traditional growth factor, fibroblast growth factor-21 (FGF21) is considered to be a metabolic hormone. In the current study, we investigated serum FGF21 levels in the self-contained population of Sorbs. Serum FGF21 concentrations were quantified by ELISA and correlated with IGF1 as well as metabolic, renal, hepatic, inflammatory, and cardiovascular parameters in 913 Sorbs from Germany. Moreover, human IGF1 protein secretion was investigated in FGF21-stimulated HepG2 cells. Median FGF21 serum concentrations were 2.1-fold higher in subjects with type 2 diabetes mellitus (141.8 ng/l) compared with controls (66.7 ng/l). Furthermore, nondiabetic subjects with FGF21 levels below the detection limit of the ELISA showed a more beneficial metabolic profile compared with subjects with measurable FGF21. Moreover, FGF21 was significantly lower in female compared with male subjects after adjustment for age and BMI. In multiple regression analyses, circulating FGF21 concentrations remained independently and positively associated with gender, systolic blood pressure, triglycerides, and γ glutamyl transferase whereas a negative association was observed with IGF1 in nondiabetic subjects. Notably, FGF21 significantly inhibited IGF1 secretion into HepG2 cell culture supernatants in preliminary in vitro experiments. FGF21 serum concentrations are associated with facets of the metabolic syndrome, hepatocellular function, as well as GH status.

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 adipocyte fatty acid-binding protein are decreased in chronic pancreatitis.

OBJECTIVE: Chronic pancreatitis (CP) is associated with an increased risk for diabetes mellitus and vascular disease. Adipocyte fatty acid-binding protein (AFABP) is a novel adipokine that is independently associated with the metabolic syndrome and cardiovascular disease. In the current study, we investigated serum AFABP levels in CP patients compared with sex- and body mass index-matched controls. METHODS: Adipocyte fatty acid-binding protein was determined with enzyme-linked immunosorbent assay in control subjects (n = 60) and diabetic as well as nondiabetic CP (n = 60) patients and correlated to clinical and biochemical measures of glucose and lipid metabolism, as well as renal function in both groups. RESULTS: Median serum AFABP levels were significantly lower in CP patients compared with controls (12.5 vs 20.9 µg/L, P = 0.003). Furthermore, body mass index, sex, and CP independently predicted circulating AFABP. In contrast, no significant difference in circulating AFABP could be demonstrated between diabetic and nondiabetic CP patients. CONCLUSIONS: Circulating AFABP is paradoxically lower in CP patients and does not depend on pancreatic diabetes. Our data do not support a role of circulating AFABP in metabolic and vascular risk in CP patients.

Serum levels of the adipokine chemerin are increased in preeclampsia during and 6 months after pregnancy.

UNLABELLED: Preeclampsia is a serious cardiovascular complication in pregnancy which is associated with an increased future metabolic and cardiovascular risk for mother and newborn. Recently, chemerin was introduced as a novel adipokine inducing insulin resistance in vitro and in vivo. In the current study, we investigated serum concentrations of chemerin by ELISA in control and preeclampsia patients during pregnancy ( CONTROL: n=37, preeclampsia: n=37) and 6 months after delivery ( CONTROL: n=35, preeclampsia: n=36). Furthermore, the association between chemerin and markers of renal function, glucose and lipid metabolism, as well as inflammation was studied in pregnant patients. Median maternal chemerin concentrations were significantly elevated in preeclampsia patients (249.5 [range: 123.1-366.9] µg/l) as compared to controls (204.8 [138.5-280.8] µg/l) (p<0.001). Furthermore, chemerin serum levels positively correlated with blood pressure, creatinine, free fatty acids, cholesterol, triglycerides (TG), leptin, adiponectin, and C-reactive protein in univariate analyses. In multivariate analyses, TG and leptin remained independently associated with circulating chemerin. Interestingly, median chemerin concentrations 6 months after delivery remained significantly higher in former preeclampsia patients (196.0 [119.8-368.7] µg/l) as compared to controls (152.2 [102.8-216.4] µg/l). Taken together, maternal chemerin serum concentrations are significantly increased in preeclampsia during and after pregnancy. Furthermore, TG and leptin are independent predictors of circulating chemerin during pregnancy.