A Method to isolate omental adipose stem cells in pediatric patients: perspectives in investigating the pathogenesis of metabolic syndrome

Il tessuto adiposo è coinvolto nella regolazione di metabolismo glucidico e lipidico, omeostasi energetica, infiammazione e risposta immune. L’obesità addominale gioca un ruolo chiave nella regolazione dello sviluppo dell’ insulino-resistenza per l’elevata lipolisi del tessuto adiposo viscerale e la secrezione della adipochine. Gli individui nati con basso peso alla nascita tendono ad avere una redistribuzione centrale del tessuto adiposo e sono ad alto rischio di sviluppare sindrome metabolica, diabete di tipo 2 e patologie cardiovascolari. Diversi studi volti a caratterizzare le cellule staminali di derivazione adipocitaria e la loro capacità di differenziamento sono stati effettuati sul tessuto adiposo sottocutaneo e viscerale di individui obesi. Nessuno studio è stato finora eseguito sul tessuto adiposo viscerale di soggetti pediatrici. La ragione principale è che la quantità di tessuto adiposo prelevabile dai bambini non è tale da consentire l’estrazione delle cellule staminali. Scopo di questo studio è stato stabilire un metodo per isolare cellule staminali di derivazione adipocitaria da campioni molto piccoli di tessuto adiposo omentale, ottenuto da bambini sottoposti a interventi di chirurgia addominale. Abbiamo stabilito un metodo riproducibile per isolare tali cellule da campioni pediatrici di tessuto adiposo omentale. La natura mesenchimale delle cellule è stata confermata dal loro profilo antigenico di superficie. Le cellule sono state inoltre sottoposte a differenziamento adipogenico e osteogenico in vitro. La disponibilità di linee di cellule staminali ottenute da tessuto adiposo omentale di soggetti in età pediatrica apre il sipario per ricerche future con l’intento di chiarire se la programmazione fetale dell’adipogenesi possa giocare un ruolo chiave nella patogenesi dell’origine fetale della sindrome metabolica, del diabete di tipo 2 e delle patologie cardiovascolari. Pertanto, la caratterizzazione di tali cellule potrebbe fornire maggiore comprensione del rischio metabolico correlato al ritardo di crescita ad inizio intrauterino, con potenziali implicazioni nella prevenzione delle alterazioni metaboliche a lungo termine.Adipose tissue is involved in the regulation of glucose and lipid metabolism, energy balance, inflammation and immune response. Abdominal obesity plays a key role in the development of insulin-resistance due to the high lipolytic rate of visceral adipose tissue and its secretion of adipocytokines. Subjects with low birth weight are prone to central redistribution of adipose tissue and are at high risk of developing metabolic syndrome, type 2 diabetes and cardiovascular disease. Several investigations refer to the physiology and pathophysiology of subcutaneous and visceral adipose tissue of adult obese subjects, focusing on the characterization of adipose-derived stem cells and their differentiation capacity. No study has been carried out so far on the visceral adipose tissue of paediatric patients. The main limitation is the amount of fat tissue available from children, adipose stem cells can be extracted from. Aim of this investigation was to establish a method to successfully isolate adipose stem cells from very small specimens of omental fat obtained from children undergoing abdominal surgery. procedure employed to extract adipose stem cells from large amounts of lipoaspirate. We established a feasible method to isolate adipose stem cells from paediatric specimens of omental fat. The mesenchymal nature was confirmed by the surface antigenic profile of these cells. Cells also underwent adipogenic and osteogenic differentiation in vitro. The availability of stem cell lines from omental adipose tissue of paediatric subjects sets up the stage for future investigations aimed to unravel whether a fetal programming of adipogenesis may play a key role in the pathogenesis of fetal origin of metabolic syndrome, type 2 diabetes and cardiovascular disease. Therefore, the knowledge of the behavior of visceral adipose tissue derived stem cells could provide more understanding of the metabolic risk related to intrauterine growth retardation, with potential clinical implications in the prevention of long-term metabolic alterations

Adipose Tissue: A Metabolic Regulator. Potential Implications for the Metabolic Outcome of Subjects Born Small for Gestational Age (SGA)

Adipose tissue is involved in the regulation of glucose and lipid metabolism, energy balance, inflammation and immune response. Abdominal obesity plays a key role in the development of insulin resistance because of the high lipolytic rate of visceral adipose tissue and its secretion of adipocytokines. Low birth weight subjects are prone to central redistribution of adipose tissue and are at high risk of developing metabolic syndrome, type 2 diabetes and cardiovascular disease. Intrauterine adipogenesis may play a key role in the fetal origin of the pathogenesis of metabolic syndrome, type 2 diabetes and cardiovascular disease. Therefore, knowledge of the behavior of visceral adipose tissue-derived stem cells could provide a greater understanding of the metabolic risk related to intrauterine growth retardation, with potential clinical implications for the prevention of long-term metabolic alterations

A narrative review on pathogenetic mechanisms of hyperinsulinemic hypoglycemia in Kabuki syndrome

Objective. Kabuki syndrome (KS) is associated with hyperinsulinemic hypoglycemia (HH) in 0.3–4% of patients, thus exceeding the prevalence in the general population. HH association is stronger for KS type 2 (KDM6A-KS, OMIM #300867) than KS type 1 (KMT2D-KS, OMIM #147920). Both the disease-associated genes, KMD6A and KMT2D, modulate the chromatin dynamic. As such, KS is considered to be the best characterized pediatric chromatinopathy. However, the exact pathogenetic mechanisms leading to HH in this syndrome remain still unclear

Role of Pescadillo and Upstream Binding Factor in the Proliferation and Differentiation of Murine Myeloid Cells

Pescadillo (PES1) and the upstream binding factor (UBF1) play a role in ribosome biogenesis, which regulates cell size, an important component of cell proliferation. We have investigated the effects of PES1 and UBF1 on the growth and differentiation of cell lines derived from 32D cells, an interleukin-3 (IL-3)-dependent murine myeloid cell line. Parental 32D cells and 32D IGF-IR cells (expressing increased levels of the type 1 insulin-like growth factor I [IGF-I] receptor [IGF-IR]) do not express insulin receptor substrate 1 (IRS-1) or IRS-2. 32D IGF-IR cells differentiate when the cells are shifted from IL-3 to IGF-I. Ectopic expression of IRS-1 inhibits differentiation and transforms 32D IGF-IR cells into a tumor-forming cell line. We found that PES1 and UBF1 increased cell size and/or altered the cell cycle distribution of 32D-derived cells but failed to make them IL-3 independent. PES1 and UBF1 also failed to inhibit the differentiation program initiated by the activation of the IGF-IR, which is blocked by IRS-1. 32D IGF-IR cells expressing PES1 or UBF1 differentiate into granulocytes like their parental cells. In contrast, PES1 and UBF1 can transform mouse embryo fibroblasts that have high levels of endogenous IRS-1 and are not prone to differentiation. Our results provide a model for one of the theories of myeloid leukemia, in which both a stimulus of proliferation and a block of differentiation are required for leukemia development

Hepatic glycogen storage diseases type 0, VI and IX: description of an italian cohort

Abstract Background Glycogen storage disease (GSD) type 0, VI and IX are inborn errors of metabolism involving hepatic glycogen synthesis and degradation. We performed a characterization of a large Italian cohort of 30 patients with GSD type 0a, VI, IXa, IXb and IXc. A retrospective evaluation of genetical, auxological and endocrinological data, biochemical tests, and nutritional intakes was assessed. Eventual findings of overweight/obesity and insulin-resistance were correlated with diet composition. Results Six GSD-0a, 1 GSD-VI, and 23 GSD-IX patients were enrolled, with an age of presentation from 0 to 72 months (median 14 months). Diagnosis was made at a median age of 30 months, with a median diagnostic delay of 11 months and a median follow-up of 66 months. From first to last visit, patients gained a median height of 0.6 SDS (from − 1.1 to 2.1 SDS) and a median weight of 0.5 SDS (from − 2.5 to 3.3 SDS); mean and minimal glucose values significant improved (p < 0.05). With respect to dietary intakes, protein intake (g/kg) and protein intake (g/kg)/RDA ratio directly correlated with the glucose/insulin ratio (p < 0.05) and inversely correlated with HOMA-IR (Homeostasis model assessment of insulin resistance, p < 0.05), BMI SDS (p < 0.05) and %ibw (ideal body weight percentage, p < 0.01). Conclusion A prompt establishment of specific nutritional therapy allowed to preserve growth, improve glycemic control and prevent liver complication, during childhood. Remarkably, the administration of a high protein diet appeared to have a protective effect against overweight/obesity and insulin-resistance

Educational Interventions on Pregnancy Vaccinations during Childbirth Classes Improves Vaccine Coverages among Pregnant Women in Palermo&rsquo;s Province

Maternal immunization is considered the best intervention in order to prevent influenza infection of pregnant women and influenza and pertussis infection of newborns. Despite the existing recommendations, vaccination coverage rates in Italy remain very low. Starting from August 2018, maternal immunization against influenza and diphtheria-tetanus-pertussis were strongly recommended by the Italian Ministry of Health. We conducted a cross sectional study to estimate the effectiveness of an educational intervention, conducted during childbirth classes in three general hospitals in the Palermo metropolitan area, Italy, on vaccination adherence during pregnancy. To this end, a questionnaire on knowledge, attitudes, and immunization practices was structured and self-administered to a sample of pregnant women attending childbirth classes. Then, an educational intervention on maternal immunization, followed by a counseling, was conducted by a Public Health medical doctor. After 30 days following the interventions, the adherence to the recommended vaccinations (influenza and pertussis) was evaluated. At the end of the study 326 women were enrolled and 201 responded to the follow-up survey. After the intervention, among the responding pregnant women 47.8% received influenza vaccination (+44.8%), 57.7% diphtheria-tetanus-pertussis vaccination (+50.7%) and 64.2% both the recommended vaccinations (+54.8%). A significant association was found between pregnant women that received at least one vaccination during pregnancy and higher educational level (graduation degree/master&rsquo;s degree), employment status (employed part/full-time) and influenza vaccination adherence during past seasons (at least one during last five years). The implementation of vaccination educational interventions, including counseling by healthcare professionals (HCPs), on maternal immunization during childbirth courses improved considerably the vaccination adherence during pregnancy