Evidence for a Relationship between VEGF and BMI Independent of Insulin Sensitivity by Glucose Clamp Procedure in a Homogenous Group Healthy Young Men

BACKGROUND: This is the first study to experimentally explore the direct relationship between circulating VEGF levels and body mass index (BMI) as well as to unravel the role of insulin sensitivity in this context under standardized glucose clamp conditions as the methodical gold-standard. In order to control for known influencing factors such as gender, medication, and arterial hypertension, we examined a highly homogeneous group of young male subjects. Moreover, to encompass also subjects beyond the normal BMI range, low weight and obese participants were additionally included and stress hormones as a main regulator of VEGF were assessed. METHODOLOGY/PRINCIPAL FINDINGS: Under euglycemic clamp conditions, VEGF was measured in 15 normal weight (BMI 20-25 kg/m(2)), 15 low weight (BMI<20 kg/m(2)), and 15 obese (BMI>30 kg/m(2)) male subjects aged 18-30 years and the insulin sensitivity index (ISI) was calculated. Since stress axis activation promotes VEGF secretion, concentrations of ACTH, cortisol, and catecholamines were monitored. Despite of comparable ACTH (P = 0.145), cortisol (P = 0.840), and norepinephrine (P = 0.065) levels, VEGF concentrations differed significantly between BMI-groups (P = 0.008) with higher concentrations in obese subjects as compared to normal weight (P = 0.061) and low weight subjects (P = 0.002). Pearson's correlation analysis revealed a positive relationship between BMI and VEGF levels (r = 0.407; P = 0.010) but no correlation of VEGF with ISI (r = 0.224; P = 0.175). CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a positive correlation between concentrations of circulating VEGF levels and BMI in healthy male subjects under highly controlled conditions. This relationship which is apparently disconnected from insulin sensitivity may be part of some pathogenetic mechanisms underlying obesity and type 2 diabetes

Distinct Characteristics of Circulating Vascular Endothelial Growth Factor-A and C Levels in Human Subjects

The mechanisms that lead from obesity to atherosclerotic disease are not fully understood. Obesity involves angiogenesis in which vascular endothelial growth factor-A (VEGF-A) plays a key role. On the other hand, vascular endothelial growth factor-C (VEGF-C) plays a pivotal role in lymphangiogenesis. Circulating levels of VEGF-A and VEGF-C are elevated in sera from obese subjects. However, relationships of VEGF-C with atherosclerotic risk factors and atherosclerosis are unknown. We determined circulating levels of VEGF-A and VEGF-C in 423 consecutive subjects not receiving any drugs at the Health Evaluation Center. After adjusting for age and gender, VEGF-A levels were significantly and more strongly correlated with the body mass index (BMI) and waist circumference than VEGF-C. Conversely, VEGF-C levels were significantly and more closely correlated with metabolic (e.g., fasting plasma glucose, hemoglobin A1c, immunoreactive insulin, and the homeostasis model assessment of insulin resistance) and lipid parameters (e.g., triglycerides, total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), and non-high-density-lipoprotein cholesterol (non-HDL-C)) than VEGF-A. Stepwise regression analyses revealed that independent determinants of VEGF-A were the BMI and age, whereas strong independent determinants of VEGF-C were age, triglycerides, and non-HDL-C. In apolipoprotein E-deficient mice fed a high-fat-diet (HFD) or normal chow (NC) for 16 weeks, levels of VEGF-A were not significantly different between the two groups. However, levels of VEGF-C were significantly higher in HFD mice with advanced atherosclerosis and marked hypercholesterolemia than NC mice. Furthermore, immunohistochemistry revealed that the expression of VEGF-C in atheromatous plaque of the aortic sinus was significantly intensified by feeding HFD compared to NC, while that of VEGF-A was not. In conclusion, these findings demonstrate that VEGF-C, rather than VEGF-A, is closely related to dyslipidemia and atherosclerosis

Parents' psychological adjustment in families of children with Spina Bifida: a meta-analysis

BACKGROUND: Spina Bifida (SB) is the second most common birth defect worldwide. Since the chances of survival in children with severe SB-forms have increased, medical care has shifted its emphasis from life-saving interventions to fostering the quality of life for these children and their families. Little is known, however, about the impact of SB on family adjustment. Reviewers have struggled to synthesize the few contradictory studies available. In this systematic review a new attempt was made to summarize the findings by using meta-analysis and by delimiting the scope of review to one concept of family adjustment: Parents' psychological adjustment. The questions addressed were: (a) do parents of children with SB have more psychological distress than controls? (b) do mothers and fathers differ? and (c) which factors correlate with variations in psychological adjustment? METHODS: PsycInfo, Medline, and reference lists were scanned. Thirty-three relevant studies were identified of which 15 were eligible for meta-analysis. RESULTS: SB had a negative medium-large effect on parents' psychological adjustment. The effect was more heterogeneous for mothers than for fathers. In the reviewed studies child factors (age, conduct problems, emotional problems, and mental retardation), parent factors (SES, hope, appraised stress, coping, and parenting competence), family factors (family income, partner relationship, and family climate), and environmental factors (social support) were found to be associated with variations in parents' psychological adjustment. CONCLUSION: Meta-analysis proved to be helpful in organizing studies. Clinical implications indicate a need to be especially alert to psychological suffering in mothers of children with SB. Future research should increase sample sizes through multi-center collaborations

Leitlinienprogramme in Deutschland

Brain energy consumption induced by electrical stimulation increases systemic glucose tolerance in normal-weight men. In obesity, fundamental reductions in brain energy levels, gray matter density, and cortical metabolism, as well as chronically impaired glucose tolerance, suggest that disturbed neuroenergetic regulation may be involved in the development of overweight and obesity. Here, we induced neuronal excitation by anodal transcranial direct current stimulation versus sham, examined cerebral energy consumption with 31P magnetic resonance spectroscopy, and determined systemic glucose uptake by euglycemic-hyperinsulinemic glucose clamp in 15 normal-weight and 15 obese participants. We demonstrate blunted brain energy consumption and impaired systemic glucose uptake in obese compared with normal-weight volunteers, indicating neuroenergetic dysregulation in obese humans. Broadening our understanding of reduced multifocal gray matter volumes in obesity, our findings show that reduced appetite- and taste-processing area morphometry is associated with decreased brain energy levels. Specifically, gray matter volumes of the insula relate to brain energy content in obese participants. Overall, our results imply that a diminished cerebral energy supply may underlie the decline in brain areas assigned to food intake regulation and therefore the development of obesity

Messung und Modellierung des Waermetransportes bei Formgebungsprozessen unter besonderer Beruecksichtigung der Waermeuebergangskoeffizienten und des Waermetransportes durch Strahlung Schlussbericht

Available from TIB Hannover: F04B1076 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEArbeitsgemeinschaft Industrieller Forschungsvereinigungen 'Otto von Guericke' e.V. (AIF), Koeln (Germany)DEGerman

Brain energy consumption induced by electrical stimulation promotes systemic glucose uptake.

BACKGROUND: Controlled transcranial stimulation of the brain is part of clinical treatment strategies in neuropsychiatric diseases such as depression, stroke, or Parkinson's disease. Manipulating brain activity by transcranial stimulation, however, inevitably influences other control centers of various neuronal and neurohormonal feedback loops and therefore may concomitantly affect systemic metabolic regulation. Because hypothalamic adenosine triphosphate-sensitive potassium channels, which function as local energy sensors, are centrally involved in the regulation of glucose homeostasis, we tested whether transcranial direct current stimulation (tDCS) causes an excitation-induced transient neuronal energy depletion and thus influences systemic glucose homeostasis and related neuroendocrine mediators.METHODS: In a crossover design testing 15 healthy male volunteers, we increased neuronal excitation by anodal tDCS versus sham and examined cerebral energy consumption with (31)phosphorus magnetic resonance spectroscopy. Systemic glucose uptake was determined by euglycemic-hyperinsulinemic glucose clamp, and neurohormonal measurements comprised the parameters of the stress systems.RESULTS: We found that anodic tDCS-induced neuronal excitation causes an energetic depletion, as quantified by (31)phosphorus magnetic resonance spectroscopy. Moreover, tDCS-induced cerebral energy consumption promotes systemic glucose tolerance in a standardized euglycemic-hyperinsulinemic glucose clamp procedure and reduces neurohormonal stress axes activity.CONCLUSIONS: Our data demonstrate that transcranial brain stimulation not only evokes alterations in local neuronal processes but also clearly influences downstream metabolic systems regulated by the brain. The beneficial effects of tDCS on metabolic features may thus qualify brain stimulation as a promising nonpharmacologic therapy option for drug-induced or comorbid metabolic disturbances in various neuropsychiatric diseases

Subjektive Beduerfnisstrukturen und Lebensqualitaet chronisch schizophrener Patienten und ihrer Angehoerigen. Bd. 1: Theoretische und methodische Grundlagen der Untersuchung Abschlussbericht

SIGLEAvailable from TIB Hannover: F01B1081 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung und Forschung, Berlin (Germany)DEGerman