leptin and Heart-Defects--Congenital

Cardiac surgery involving cardiopulmonary bypass (CPB) causes a systemic inflammatory process which can lead to multiple organ failure and postoperative morbidity. Recent animal and human studies suggested a possible involvement of leptin in the systemic inflammatory response.. To characterize the response of leptin to open heart surgery (OHS) and the relationship between the time course of leptin levels and the post-operative clinical course, and to examine the effect of exogenous glucocorticoids.. Forty-seven pediatric patients, undergoing OHS for congenital heart disease were studied. Thirty-four patients (Group 1) received methylprednisolone during CPB while 13 (group 2) did not. Serial blood samples were collected perioperatively and up to 24 h after surgery, and assayed for leptin and cortisol.. All patients' leptin levels decreased significantly during CPB (to 44-48% of baseline, p<0.001); they then increased, peaking at 12 h post-operatively. The levels of groups 1 and 2 were similar up to 8 h post-operatively; thereafter, those of group 1 were significantly higher. Recovery of leptin levels in patients with a more complicated post-operative course was comparatively slower. Cortisol levels of all patients increased significantly during CPB (p<0.001), gradually decreasing afterwards. Cortisol and leptin levels were inversely correlated in both patients' groups.. CPB is associated with acute changes in circulating leptin levels. A complicated postoperative course is associated with lower leptin levels which are inversely correlated with cortisol levels. Leptin may participate in post-CPB inflammatory and hemodynamic responses.

Topics: Adolescent; Cardiopulmonary Bypass; Child; Child, Preschool; Female; Glucocorticoids; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Inflammation; Leptin; Male; Methylprednisolone; Postoperative Complications; Postoperative Period; Prognosis; Systemic Inflammatory Response Syndrome

Failure to thrive (FTT), defined as weight or height less than the lowest 2.5 percentile for age, is prevalent in up to 66% of children with congenital heart disease (CHD). Risk stratification methods to identify those who would benefit from early intervention are currently lacking. We aimed to identify a novel growth biomarker to aid clinical decision-making in children with CHD.. This is a cross-sectional study of patients 2 months to 10 years of age with any CHD undergoing cardiac surgery. Preoperative weight-for-age Z scores (WAZ) and height-for-age Z scores (HAZ) were calculated and assessed for association with preoperative plasma biomarkers: growth differentiation factor 15 (GDF-15), fibroblast growth factor 21, leptin, prealbumin, and C-reactive protein (CRP).. Of the 238 patients included, approximately 70% of patients had WAZ/HAZ < 0 and 34% had FTT. There was a moderate correlation between GDF-15 and WAZ/HAZ. When stratified by age, the correlation of GDF-15 to WAZ and HAZ was strongest in children under 2 years of age and persisted in the setting of inflammation (CRP > 0.5 mg/dL). Diagnoses commonly associated with congestive heart failure had high proportions of FTT and median GDF-15 levels. Prealbumin was not correlated with WAZ or HAZ.. GDF-15 represents an important growth biomarker in children with CHD, especially those under 2 years of age who have diagnoses commonly associated with CHF. Our data do not support prealbumin as a long-term growth biomarker.

Topics: Biomarkers; C-Reactive Protein; Child; Cross-Sectional Studies; Growth Differentiation Factor 15; Heart Defects, Congenital; Humans; Infant; Leptin

DEHP is a plasticizer which has been used in plastic products of everyday use for decades. Studies in mice and murine cell culture models identified DEHP as an endocrine disruptor that may also act as an obesogen. As this is of high concern in respect of the worldwide obesity epidemic, our aim is the translation of these findings into a human model system. On the basis of DOHaD, we investigated the influence of an environmentally relevant dose of DEHP [50 µg/ml] on adipogenesis in the human cell culture model SGBS. Pre-adipocytes were exposed to DEHP and differentiated into mature adipocytes. At different stages of differentiation, markers of adipogenesis like GLUT4, FABP4, LPL and PPARs, and of signaling pathways like AMPK/ACC2, JAK/STAT and MAPK were analyzed. Functional markers like adipokine secretion and triglyceride content as well as ROS production were measured in mature adipocytes. We found significantly lower expression levels of adipogenic markers, a reduction in lipid accumulation, higher leptin- and reduced adiponectin levels in the supernatant of treated adipocytes. Moreover, ROS production was significantly elevated after DEHP-exposure. In conclusion, DEHP led to lower grade of adipogenic differentiation in human SGBS-adipocytes under the chosen conditions.

Topics: Adipocytes; Adipogenesis; Adiponectin; Arrhythmias, Cardiac; Cells, Cultured; Diethylhexyl Phthalate; Fatty Acids; Genetic Diseases, X-Linked; Gigantism; Heart Defects, Congenital; Humans; Intellectual Disability; Leptin; Plasticizers; Reactive Oxygen Species; Triglycerides

Calcific aortic valve disease (CAVD) affects 2-6% of the population over 65 years, and age, gender, smoking, overweight, dyslipidemia, diabetes contribute to the development of this disease. CAVD results, in part, from the osteoblast differentiation of human valvular interstitial cells (VICs). This study aims to elucidate the effects of leptin on osteoblast phenotype of VICs and the signalling pathways involved.. Patients who underwent aortic valve replacement for CAVD (n = 43) were included in this study. Patients with coronary artery disease (CAD) without CAVD (n = 129) were used as controls.. Patients with CAVD had higher serum leptin concentrations than CAD patients (p = 0.002). Leptin was found in calcific aortic valves, with higher concentrations in calcified versus non-calcified zones (p = 0.01). Chronic leptin stimulation of human VICs enhanced alkaline phosphatase (ALP) activity and ALP, BMP-2 and RUNX2 expression and decreased osteopontin expression. Moreover, inhibiting Akt or ERK during leptin stimulation lowered the expression of osteoblast markers in VIC.. Taken together, these findings indicate that leptin plays a critical role in CAVD development by promoting osteoblast differentiation of human aortic VICs in an Akt- and ERK-dependent manner. This study highlights the role of leptin in CAVD development, and further studies are needed to determine whether reducing circulating leptin levels or blocking leptin actions on VICs is efficient to slow CAVD progression.

Topics: Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Bicuspid Aortic Valve Disease; Biomarkers; Calcinosis; Case-Control Studies; Cell Differentiation; Cell Transdifferentiation; Cells, Cultured; Female; Heart Defects, Congenital; Heart Valve Diseases; Humans; Leptin; Male; MAP Kinase Signaling System; Middle Aged; Oncogene Protein v-akt; Osteoblasts; Phenotype; Signal Transduction

To investigate the serum levels of leptin, ghrelin and tumour necrosis factor-alpha in children with cyanotic and acyanotic congenital heart disease.. The prospective cohort study, was conducted at imam Ali Hospital, Zahedan University of Medical Sciences, Iran, in 2009-10 and comprised 64 subjects, including patients and controls. Using enzyme-linked immunosorpent assay kits, serum levels of ghrelin, leptin and tumour necrosis factor-alpha were measured and compared among patients (both cyanotic and acyanotic) and the controls, SPSS version 20 was used for statistical analysis.. Of the 64 subjects, 24 (37.5%) were cyanotic, 21 (32.8%) were acynotic and 19 (29.68%) were healthy controls. The three groups were homogenous in terms of age and gender characteristics. There was no significant difference among the groups leptin, ghrelin and tumour necrosis factor-alpha serum levels (p > 0.05). There were also no significant differences in terms of weight, height and body mass index (P > 0.05).. Serum levels of ghrelin, leptin and tumour necrosis factor-alpha did not change in acyanotic and cyanotic patients with congenital heart disease, suggesting that other crucial factors may regulate individuals' nutrient intake, growth, weight and energy intake and output.

Topics: Case-Control Studies; Child; Child, Preschool; Cohort Studies; Cyanosis; Female; Ghrelin; Heart Defects, Congenital; Humans; Infant; Leptin; Male; Tumor Necrosis Factor-alpha

Adipokines play a central role in the development of diseases associated with insulin resistance and obesity. Hypoxia in adipose tissue leads to a dysregulation of the expression of adipokines. The effect of hypoxia on the more recently identified adipokine apelin in human adipocytes is unclear. Therefore, we aimed at investigating the role of hypoxia on the expression of the adipokine apelin. Differentiated human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were cultured under hypoxic conditions for varying time periods. A modular incubator chamber was used to create a hypoxic tissue culture environment (defined as 1% O(2), 94% N, and 5% CO(2)). In addition, hypoxic conditions were mimicked by using CoCl(2). The effect of hypoxia on the expression of the investigated adipokines was measured by real-time PCR and the secretion of apelin was quantified by ELISA. Induction of hypoxia significantly induced mRNA expression of leptin and apelin in differentiated SGBS adipocytes compared with the normoxic control condition. Expression of adiponectin was significantly decreased by hypoxia. In addition, the amount of secreted apelin protein in response to hypoxia was elevated compared to untreated cells. Furthermore, we could demonstrate that the observed hypoxia-induced induction of apelin mRNA expression is in the first phase dependent on HIF-1α. In our study, we could demonstrate for the first time that apelin expression and secretion by human adipocytes are strongly induced under hypoxic conditions and that the early response on hypoxia with apelin induction is dependent on HIF-1α.

Topics: Adipocytes; Adiponectin; Apelin; Arrhythmias, Cardiac; Cell Differentiation; Cell Hypoxia; Gene Expression Regulation; Genetic Diseases, X-Linked; Gigantism; Heart Defects, Congenital; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunoblotting; Intellectual Disability; Intercellular Signaling Peptides and Proteins; Leptin; RNA, Messenger

Ghrelin has effects on appetite and growth. Recent reports suggest effects on cardiac function, but no study has evaluated the ghrelin levels of congenital heart disease (CHD) infants with heart failure. The purpose of the present study was therefore to investigate the relationship between ghrelin level and growth and cardiac function in CHD infants.. Twenty-eight infants with CHD were eligible for the study. Blood samples were obtained at the time of insertion of intracardiac catheter and correlation was examined between ghrelin plasma level and anthropometric parameters, including z score of height and weight, body mass index (BMI), and %bodyweight gain rate, severity of heart failure, and the levels of leptin and insulin-like growth factor-1.. In the CHD group, active ghrelin (A-Ghr) had a significant negative correlation with z score of bodyweight, and a significant positive correlation with cardiac function. There were no correlations, however, with height and BMI. A-Ghr levels were significantly higher in the high heart failure index score group. Significant correlation between A-Ghr and desacyl-ghrelin in the CHD group was observed.. A-Ghr is involved in cardiac function and has little effect on their physique in infants with CHD.

Topics: Anthropometry; Biomarkers; Body Height; Body Weight; Case-Control Studies; Child Development; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Ghrelin; Growth; Heart Defects, Congenital; Heart Failure; Heart Function Tests; Humans; Infant; Infant, Newborn; Japan; Leptin; Male; Reference Values; Risk Assessment; Somatomedins; Statistics, Nonparametric

To investigate the relationship between serum leptin and lipid profile in South Indian School children and adolescents, and to evaluate the role of serum leptin in obese, overweight and congenital heart diseased children and adolescents; in South Indian population and its correlation with anthropometric and biochemical parameters.. The study included 185 school going children and adolescents. (52 obese, 49 overweight, 25 congenital heart disease children and adolescents, were compared with 59 normal controls, aged between 10-17 years). Anthropometric variables, lipid profile, fasting serum glucose were analyzed by autoanalyser and serum leptin by ELISA.. Serum leptin levels were significantly elevated in obese and overweight children than in control children (36.88+/-18.60ng/mL, 20.64+/-11.18ng/mL vs 7.97+/-2.79ng/mL; p value <0.001), and decreased in congenital heart diseased children than in control children (6.20+/-4.23 ng/mL vs 7.97+/-2.79ng/mL; p value <0.005).. This study provides a good relationship between serum leptin levels and anthropometric and biochemical parameters, such as total cholesterol, triglycerides and LDL-cholesterol. We observed negative correlation between serum leptin and fasting glucose levels and HDL-cholesterol levels were found to be non-significant among the groups. Further studies with large sample size are needed to ascertain the relationship between serum leptin and lipid profile in different groups of children and adolescents.

Topics: Adolescent; Analysis of Variance; Anthropometry; Biomarkers; Case-Control Studies; Child; Female; Heart Defects, Congenital; Humans; India; Leptin; Lipids; Male; Obesity; Overweight

Vascular endothelial growth factor (VEGF), platelet derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) and leptin are known as potent angiogenic factors The objective of the study was to evaluate these angiogenic factors VEGF, PD-ECGF/TP and leptin in children with congenital heart disease (CHD) and the factors that lead to angiogenesis in such cases.. Sixty CHD children were studied and divided into two groups (n=30); cyanotic-CHD (C-CHD) and acyanotic-CHD (A-CHD). Twenty five healthy children were included as controls.. Significantly higher serum levels of VEGF, PD-ECGF/TP activity and leptin were detected in patients with CHD, particularly in patients with C-CHD. CHD patients with SpO2<90%, pulmonary hypertension (PH), severe pulmonary stenosis (PS), detectable collaterals, cardiomegaly and/or heart failure showed significantly higher levels of these factors than those with higher SpO2 or those without these findings.. Hypoxia, PH and PS are important factors that lead to harmful angiogenesis. However, angiogenesis could be essential in some cases of CHD as coarctation of aorta to enhance renal perfusion. This may provide new ways for therapeutic strategies aiming at reducing or promoting angiogenesis in CHD to improve patient's outcome.

Topics: Biomarkers; Child, Preschool; Disease Progression; Echocardiography; Female; Heart Defects, Congenital; Humans; Leptin; Male; Neovascularization, Pathologic; Prognosis; Spectrophotometry; Thymidine Phosphorylase; Vascular Endothelial Growth Factor A

Leptin and interleukin-6 (IL-6) are inversely correlated and associated with decreased survival in critically ill patients. We investigated changes in leptin, IL-6, and troponin in children undergoing open-heart surgery, hypothesizing that IL-6 and troponin will increase after cardiopulmonary bypass (CPB) and will be negatively correlated with leptin.. Serial blood samples were collected from 21 patients 24 hours before and up to 48 hours after surgery.. Leptin levels decreased by 50% during CPB (P < .001), then gradually increased, reaching baseline levels 12 hours after surgery. The IL-6 levels increased (P < .001) during CPB, peaking 2 hours after surgery and remaining slightly elevated at 24 hours after surgery (P < .001). Leptin and IL-6 were negatively correlated (R = -0.448, P < .001). Troponin levels increased during CPB (P < .001). Postoperative leptin and troponin were inversely correlated (r = -0.535, P < .001). Patients with modest elevations in troponin levels (<20 microg/L) had a shorter aortic clamp and CPB time (P < .01), lower IL-6 peak levels (P = .03), and shorter duration of ventilation and inotropic support compared with patients with peak troponin levels greater than 20 microg/L.. Lower leptin and higher IL-6 levels correlated with troponin, a marker of myocardial injury. Because leptin may have cardioprotective effects, the postoperative drop in its levels may further contribute to myocardial dysfunction.

Topics: Biomarkers; Cardiopulmonary Bypass; Critical Illness; Female; Heart Defects, Congenital; Hospital Mortality; Humans; Infant; Inflammation; Interleukin-6; Leptin; Male; Myocardial Ischemia; Postoperative Complications; Prognosis; Survival Analysis; Time Factors; Troponin

To study the changes of serum leptin (LEP) and vascular endothelial growth factor (VEGF) in children with congenital heart disease(CHD) and their roles in CHD.. Forty-eight children with acyanotic CHD (ACHD group), 20 age-matched children with cyanotic CHD (CCHD group) and 20 healthy children (control group) were enrolled. The ACHD group was subdivided into two groups with (n=20) or without concurrent heart failure (n=28). Serum LEP, VEGF, total protein and albumin levels and body mass index (BMI) were measured.. Serum total protein and albumin levels were not apparently different in all CHD children from healthy controls, but there was a significant difference in the BMI between them (p<0.01). Serum LEP and VEGF levels and the ratio of LEP/BMI in all CHD children were significantly higher than those in healthy controls (p<0.01). Compared with the ACHD group without heart failure, the serum LEP and VEGF levels and the ratio of LEP/BMI in the CCHD and the ACHD with heart failure groups increased significantly (p<0.01). In the ACHD group, serum LEP level was positively correlated with BMI (p<0.01). In the CCHD group, there were positive correlations between serum LEP level and serum VEGF level (p<0.01) and between hemoglobin concentration and serum VEGF level (p<0.01). Arterial oxygen saturation was negatively correlated with serum VEGF (p<0.01) and LEP levels (p<0.01) in the CCHD group.. Both VEGF and LEP play roles in the pathophisiological process of CHD. VEGF and LEP are associated with the development of heart failure in children with ACHD.

Topics: Body Mass Index; Child; Child, Preschool; Female; Heart Defects, Congenital; Hemoglobins; Humans; Infant; Leptin; Male; Oxygen; Vascular Endothelial Growth Factor A

Leptin has been shown to be an integral component of energy homeostasis and regulation of body weight. Leptin regulates adipose tissue mass and correlates with the fat mass, however the circulating levels are altered by energy intake. Research on the physiological function of leptin has primarily focused on its role in the pathogenesis of obesity. However, its role in the negative energy imbalance is unclear. Increased energy expenditure is a primary factor in the reduced growth in infants with cyanotic congenital heart disease. The objective of this study was to examine the possible role of leptin on growth and nutrition in children with cyanotic and acyanotic congenital heart disease.. In this study, plasma leptin levels, nutritional and growth status were evaluated in 28 cyanotic and 20 acyanotic patients with congenital heart disease. Although standard deviation (S.D.) of height (P<0.01), mid arm circumference (MAC) (P<0.001) and body mass index (BMI) (P<0.05) were significantly low in cyanotic group, plasma leptin levels were similar. Energy intake was high in cyanotic group. In both cyanotic and acyanotic group, plasma leptin levels were correlated with BMI (R: 0.388, P<0.05 and R: 0.789, P<0.001, respectively). In addition, leptin levels were significantly correlated with the height (R: 0.415, P<0.05), MAC (R: 0.482, P<0.05) and BMI (R: 0.377, P<0.05) S.D. in cyanotic subjects.. Our results suggest that the leptin regulating axis is intact in cyanotic patients and leptin does not contribute to the cachexia of cyanotic heart disease.

Topics: Adolescent; Body Height; Body Mass Index; Body Weight; Cachexia; Child; Child, Preschool; Cyanosis; Energy Metabolism; Heart Defects, Congenital; Humans; Leptin; Nutritional Status

To characterize the dynamics of circulating leptin in children after cardiac surgery with cardiopulmonary bypass (CPB), which is known to induce a systemic inflammatory response.. Investigative study.. University-affiliated tertiary care hospital.. Eight children (age range, 3 months to 13 years) undergoing CPB to correct congenital heart disease.. The time courses of leptin and cortisol levels were determined. Serial blood samples were collected from the arterial catheter or from the CPB circuit preoperatively; on termination of CPB; and at 2, 4, 8, 12, 18, and 24 hours postoperatively. Plasma was recovered immediately, divided into aliquots, and frozen at -70 degrees C until use. Leptin was measured by a human leptin radioimmunoassay kit.. Leptin levels during CPB decreased to 50% of pre-CPB levels (p < 0.01). After termination of CPB, levels increased gradually and peaked at 12 hours postoperatively (10 P.M. to 1 A.M.). Cortisol levels were inversely correlated to leptin levels (p = 0.016).. CPB is associated with acute changes in circulating leptin levels. These changes parallel those in cortisol, showing an inverse relationship between leptin and cortisol, suggesting a relationship between the neurobiology of these systems that could be important for the neuroendocrine response to CPB. A prognostic role of leptin and its relationship to cortisol after CPB warrant further study.

Topics: Adolescent; Cardiopulmonary Bypass; Child; Child, Preschool; Heart Defects, Congenital; Humans; Hydrocortisone; Infant; Leptin

Leptin may be involved in the acute stress response, regulating inflammatory parameters of major importance after cardiopulmonary bypass (CPB) surgery. Critically ill patients demonstrated significant increases in leptin levels in response to stress-related cytokines (tumor necrosis factor, interleukin [IL]-1) and abolishment of the circadian rhythm of leptin secretion. We characterized the pattern of leptin secretion in the acute postoperative period in children undergoing cardiac surgery and compared the changes in leptin levels with concomitantly occurring changes in cortisol levels, IL-8, and clinical parameters.. Investigative study.. University-affiliated tertiary care hospital.. Twenty-nine consecutive patients, aged 6 days to 15 yrs, operated upon for the correction of congenital heart defects were studied. Surgery in 20 patients (group 1) involved conventional CPB techniques, and 9 (group 2) underwent closed-heart surgery. The time courses of leptin, cortisol, and IL-8 levels were determined. Serial blood samples were collected preoperatively, on termination of CPB, and at six time points postoperatively. Plasma was recovered immediately, aliquoted, and frozen at -70 degrees C until use.. The leptin levels in group 1 decreased during CPB to 51% of baseline (p <.001), then gradually increased, reaching 120% of baseline levels at 12-18 hrs postoperatively (p <.001), returning to baseline levels at 24 hrs (p <.01). In patients undergoing closed-heart surgery (group 2), leptin levels displayed a pattern resembling the first group: they decreased during surgery to 71% of baseline levels (p =.002) and showed a tendency to return to baseline thereafter. All group 1 patients' cortisol levels increased significantly during the first hour of surgery, then decreased, returning to baseline levels at 18-24 hrs postoperatively. There was a significant negative correlation between leptin and cortisol levels (r = -2.8, p <.01). In group 2, cortisol levels increased during and after surgery, peaking 4 hrs postoperatively and decreasing thereafter. IL-8 levels determined in 15 group 1 patients increased significantly during CPB, peaked at the end of surgery, and then decreased but remained slightly elevated even at 48 hrs postoperatively. There was a significant correlation between cortisol and IL-8 levels (r = 2.55, p <.05). Children with leukocytosis, tachycardia, and hypotension had lower leptin levels and less variation over time as opposed to those with an uncomplicated course.. CPB is associated with acute changes in circulating leptin levels. These changes parallel those in cortisol, demonstrating an inverse relationship between leptin and cortisol. Further studies of the prognostic and therapeutic roles of leptin after CPB should be investigated.

Topics: Adolescent; Analysis of Variance; Cardiopulmonary Bypass; Case-Control Studies; Child; Child, Preschool; Heart Defects, Congenital; Humans; Hydrocortisone; Infant; Infant, Newborn; Interleukin-8; Leptin; Stress, Physiological