Metabolic factors in obesity

Obesity has a rising prevalence in children and adolescents, affecting 30% of the paediatric population in Portugal. Leptin is an important hormone involved in the pathogenesis of obesity and has been under investigation as a risk marker for future complications. AIMS: 1. To evaluate the relation between serum leptin levels and body mass index (BMI) and height. 2. To compare leptin levels in obese and non-obese children. 3. To evaluate the relation between leptin levels and insulin resistance index. METHODS: Cross-sectional study, using a sample of 70 obese children and a control group of 53 non-obese children. Obesity was defined as BMI standard deviation > 2 for age and sex. In the obese group we assessed sex, age, BMI SDS and height SDS for age and sex, and serum levels of glucose, insulin and leptin. In the control group were obtained BMI SDS and height SDS for age and sex and leptin levels. Data were analysed using SPSS 12. RESULTS: The mean age of obese and non-obese children was 10.3 +/- 2.9 versus 10.9 +/- 3.5 years. In the obese group, 32 (45.7%) were boys versus 18 (31.0%) in the non-obese group. BMI SDS in the obese group was 3.12 +/- 0.60 versus 0.20 +/- 0.99 in the non-obese group (p < 0.001). Leptin levels showed a positive correlation with BMI SDS (r = 0.69; p < 0.001) and height SDS (r = 0.31; p < 0.001). When comparing leptin levels between obese and non-obese groups, we found a significant difference in boys (50.7 +/- 27.3 versus 7.0 +/- 6.8 ng/ml; p < 0.001) and in girls (57.6 +/- 25.5 versus 16.5 +/- 10.3 ng/ml; p < 0.001). In the nonobese group, leptin levels were lower in boys. This difference was not seen in the obese group. Leptin showed a positive correlation with insulin resistance index in boys (r = 0.45, p = 0.05), but not in girls. CONCLUSIONS: This study has confirmed a positive correlation between leptin levels and BMI SDS. In obese children elevated leptin is associated with central resistance to its action. The positive correlation of leptin with insulin resistance index may suggest a major role of leptin in insulin resistance.info:eu-repo/semantics/publishedVersio

Binuclear Dioxomolybdenum(VI) Complex Based on Bis(2-pyridinecarboxamide) Ligand as Effective Catalyst for Fuel Desulfurization

Funding Information: The authors acknowledge ChiraTecnics ( http://www.chiratecnics.com ) for the supply of the chiral diamine ligand used to generate the Mo catalyst. Authors thank Anthony Burke (University of Coimbra) and Isabel S. Gon\u00E7alves (CICECO, University of Aveiro) for valuable discussions on catalyst formation and behaviour. Publisher Copyright: © 2024 by the authors.A binuclear dioxomolybdenum catalyst [(MoO2Cl2)2(L)] (1) (with L (1S,2S)-N,N′-bis(2-pyridinecarboxamide)-1,2-cyclohexane) was prepared and used as catalyst for the desulfurization of a multicomponent model fuel containing the most refractory sulfur compounds in real fuels. This complex was shown to have a high efficiency to oxidize the aromatic benzothiophene derivative compounds present in fuels, mainly using a biphasic 1:1 model fuel/MeOH system. This process conciliates catalytic oxidative and extractive desulfurization, resulting in the oxidation of the sulfur compounds in the polar organic solvent. The oxidative catalytic performance of (1) was shown to be influenced by the presence of water in the system. Using 50% aq. H2O2, it was possible to reuse the catalyst and the extraction solvent, MeOH, during ten consecutive cycles without loss of desulfurization efficiency.publishersversionpublishe

Abnormalities of sodium handling and of cardiovascular adaptations during high salt diet in patients with mild heart failure.

BACKGROUND: Sodium retention and hormonal activation are fundamental hallmarks in congestive heart failure. The present study was designed to assess the ability of patients with asymptomatic to mildly symptomatic heart failure and no signs or symptoms of congestion to excrete ingested sodium and to identify possible early abnormalities of hormonal and hemodynamic mechanisms related to sodium handling. METHODS AND RESULTS: The effects of a high salt diet (250 mEq/day for 6 days) on hemodynamics, salt-regulating hormones, and renal excretory response were investigated in a balanced study in 12 untreated patients with idiopathic or ischemic dilated cardiomyopathy and mild heart failure (NYHA class I-II, ejection fraction < 50%) (HF) and in 12 normal subjects, who had been previously maintained a 100 mEq/day NaCl diet. In normal subjects, high salt diet was associated with significant increases of echocardiographically measured left ventricular end-diastolic volume, ejection fraction, and stroke volume (all P < .001) and with a reduction of total peripheral resistance (P < .001). In addition, plasma atrial natriuretic factor (ANF) levels increased (P < .05), and plasma renin activity and aldosterone concentrations fell (both P < .001) in normals in response to salt excess. In HF patients, both left ventricular end-diastolic and end-systolic volumes increased in response to high salt diet, whereas ejection fraction and stroke volume failed to increase, and total peripheral resistance did not change during high salt diet. In addition, plasma ANF levels did not rise in HF in response to salt loading, whereas plasma renin activity and aldosterone concentrations were as much suppressed as in normals. Although urinary sodium excretions were not significantly different in the two groups, there was a small but systematic reduction of daily sodium excretion in HF, which resulted in a significantly higher cumulative sodium balance in HF than in normals during the high salt diet period (P < .001). CONCLUSIONS: These results show a reduced ability to excrete a sodium load and early abnormalities of cardiac and hemodynamic adaptations to salt excess in patients with mild heart failure and no signs or symptoms of congestion

Congenital hyperinsulinism and novel KDM6A duplications - resolving pathogenicity with genome and epigenetic analyses

This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this recordData availability: Restrictions apply to the availability of some or all data generated or analyzed during this study to preserve patient confidentiality or because they were used under license. The corresponding author will on request detail the restrictions and any conditions under which access to some data may be provided. The KDM6A variants reported in this study were uploaded to Decipher database (https://www.deciphergenomics.org/). Sequencing data can be used to identify individuals and are therefore available only through collaboration to experienced teams working on approved studies examining the mechanisms, cause, diagnosis and treatment of diabetes and other beta cell disorders. Requests for collaboration will be considered by a steering committee following an application to the Genetic Beta Cell Research Bank (https://www.diabetesgenes.org/current-research/genetic-beta-cell-research-bank/). Contact by email should be directed to S. Flanagan ([email protected]). We used the Genome Reference Consortium Human Build 37 (GRCh37) to annotate genetic data (accession number GCF_000001405.13). Details of this assembly are provided at: https://www.ncbi.nlm.nih.gov/assembly/GCF_000001405.13/CONTEXT: Hyperinsulinemic hypoglycemia (HI) can be the presenting feature of Kabuki syndrome (KS), which is caused by loss-of-function variants in KMT2D or KDM6A. As these genes play a critical role in maintaining methylation status in chromatin, individuals with pathogenic variants have a disease-specific epigenomic profile -an episignature. OBJECTIVE: We evaluated the pathogenicity of three novel partial KDM6A duplications identified in three individuals presenting with neonatal-onset HI without typical features of KS at the time of genetic testing. METHODS: Three different partial KDM6A duplications were identified by routine targeted next generation sequencing for HI and initially classified as variants of uncertain significance (VUS) as their location, and hence their impact on the gene, was not known. Whole genome sequencing (WGS) was undertaken to map the breakpoints of the duplications with DNA methylation profiling performed in two individuals to investigate the presence of a KS-specific episignature. RESULTS: WGS confirmed the duplication in proband 1 as pathogenic as it caused a frameshift in the normal copy of the gene leading to a premature termination codon. The duplications identified in probands 2 and 3 did not alter the reading frame and therefore their significance remained uncertain after WGS. Subsequent DNA methylation profiling identified a KS-specific episignature in proband 2 but not in proband 3. CONCLUSIONS: Our findings confirm a role for KDM6A partial gene duplications in the etiology of KS and highlight the importance of performing in-depth molecular genetic analysis to properly assess the clinical significance of VUS's in the KDM6A gene.Wellcome TrustNational Institute for Health and Care Research (NIHR)European Society for Paediatric Endocrinology (ESPE)Foundation for Paediatric ResearchDiabetes UKBreakthrough T1