Presence of anti-ADAMTS13 antibodies in obesity.

Background: The low-grade chronic inflammation present in obesity has been recognized as a risk factor for thrombosis, atherosclerosis and cardiovascular complications. In this context, production by adipose organ of a number of inflammatory adipokines could play a crucial role. It has been reported that obesity represents a risk factor for acquired thrombotic thrombocytopenic purpura (TTP), a disease caused by ADAMTS13 deficiency because of anti-ADAMTS13 antibodies, but the pathophysiological link between obesity and TTP is still unknown.

Sustained exendin-4 secretion through gene therapy targeting salivary glands in two different rodent models of obesity/type 2 diabetes.

Exendin-4 (Ex-4) is a Glucagon-like peptide 1 (GLP-1) receptor agonist approved for the treatment of Type 2 Diabetes (T2DM), which requires daily subcutaneous administration. In T2DM patients, GLP-1 administration is reported to reduce glycaemia and HbA1c in association with a modest, but significant weight loss. The aim of present study was to characterize the site-specific profile and metabolic effects of Ex-4 levels expressed from salivary glands (SG) in vivo, following adeno-associated virus-mediated (AAV) gene therapy in two different animal models of obesity prone to impaired glucose tolerance and T2DM, specifically, Zucker fa/fa rats and high fed diet (HFD) mice.

Genes implicated in insulin resistance are down-regulated in primary aldosteronism patients.

Primary aldosteronism (PA) patients display an increased incidence of insulin resistance. Herein we demonstrate the decreased gene expression of lipid metabolism genes PCK1, PLIN, ADIPOQ and PPARG in the visceral adipose tissue (VAT) of PA patients compared to age-, sex- and BMI-matched controls. In VAT, the expression of PCK1, PLIN, ADIPOQ and PPARG was inversely correlated with aldosterone levels; furthermore, PLIN and ADIPOQ gene expression was correlated with potassium levels.

Ambulatory arterial stiffness indexes in acromegaly.

Objective: Acromegaly is associated with increased cardiovascular morbidity and mortality and with specific heart and vascular abnormalities. The aim of our study was to investigate arterial stiffness using the ambulatory arterial stiffness index (AASI) and symmetric AASI (Sym-AASI), two indexes derived from 24-h ambulatory blood pressure monitoring (ABPM), in a group of normotensive and hypertensive patients with active acromegaly, compared with normotensive controls (NOR-CTR) or hypertensive controls (HYP-CTR).

Subjects And Methods: Ninety-six consecutive patients with active acromegaly (46 males, mean age 49±14 years) underwent 24-h ABPM and evaluation of cardiovascular risk factors.

Stem-cell therapy in an experimental model of pulmonary hypertension and right heart failure: role of paracrine and neurohormonal milieu in the remodeling process.

Background: In this study we investigated the effect of human amniotic fluid stem (hAFS) cells and rat adipose tissue stromal vascular fraction GFP-positive cell (rSVC-GFP) therapy and the contribution of the paracrine and neurohormonal milieu to cardiac and pulmonary vascular remodeling in a rat model of pulmonary hypertension (PH) and right heart failure (RHF).

Methods: Sprague-Dawley rats were injected with monocrotaline (MCT). Four million hAFS or rSVC-GFP cells were injected via the tail vein 3 weeks after MCT.

The progression from obesity to type 2 diabetes in Alström syndrome.

Background: Alström syndrome (ALMS) is a rare autosomal recessive monogenic disease associated with obesity, hyperinsulinemia, and alterations of glucose metabolism that often lead to the development of type 2 diabetes at a young age.

Objective: To study the relationship between weight and metabolism in a group of ALMS patients and matched controls.

Research Design And Methods: Fifteen ALMS patients (eight males, seven females; aged 3-51) were compared in a cross-sectional study with an age- and weight-matched control population.

ALMS1-deficient fibroblasts over-express extra-cellular matrix components, display cell cycle delay and are resistant to apoptosis.

Alström Syndrome (ALMS) is a rare genetic disorder (483 living cases), characterized by many clinical manifestations, including blindness, obesity, type 2 diabetes and cardiomyopathy. ALMS is caused by mutations in the ALMS1 gene, encoding for a large protein with implicated roles in ciliary function, cellular quiescence and intracellular transport. Patients with ALMS have extensive fibrosis in nearly all tissues resulting in a progressive organ failure which is often the ultimate cause of death.

Insulin signaling in adipose tissue of patients with primary aldosteronism.

Objective: We studied phosphorylation of insulin-receptors substrate downstream molecules: 1) in the ex-vivo visceral adipose tissue (VAT) of patients with aldosterone-producing adenoma (APA) (no.=7) and non-functioning adenoma (NFA) (no.=7) undergoing laparoscopic adrenalectomy; 2) in aldosterone-treated sc adipocytes of subjects (no.

A dose-response elevation in hepatic glucose uptake is paralleled by liver triglyceride synthesis and release.

Background And Aims: Enhanced release of triglycerides (TG) by the liver is implicated in the pathogenesis of the metabolic syndrome. The aim of the study was to evaluate whether a primary elevation in hepatic glucose utilization (HGU), as induced by an acute rise in circulating glucose values during physiological hyperinsulinemia, promotes TG synthesis in spite of the reduction in free fatty acids (FFA) levels.

Methods: Glucose dose-response studies were conducted in anesthetized pigs using positron emission tomography (PET) to quantify HGU during fasting euglycemic conditions (EF), and under two-step hyperglycemic hyperinsulinemia (1st-HH +3.

Cannabinoid receptor stimulation impairs mitochondrial biogenesis in mouse white adipose tissue, muscle, and liver: the role of eNOS, p38 MAPK, and AMPK pathways.

Objective: Cannabinoid type 1 (CB1) receptor is involved in whole-body and cellular energy metabolism. We asked whether CB1 receptor stimulation was able to decrease mitochondrial biogenesis in different metabolically active tissues of obese high-fat diet (HFD)-fed mice.

Research Design And Methods: The effects of selective CB1 agonist arachidonyl-2-chloroethanolamide (ACEA) and endocannabinoids anandamide and 2-arachidonoylglycerol on endothelial nitric oxide synthase (eNOS) expression were examined, as were mitochondrial DNA amount and mitochondrial biogenesis parameters in cultured mouse and human white adipocytes.

High-fat feeding stimulates endocrine, glucose-dependent insulinotropic polypeptide (GIP)-expressing cell hyperplasia in the duodenum of Wistar rats.

Aims/hypothesis: Incretins are hormones released by enteroendocrine cells in response to meals, depending upon absorption of nutrients. The present study aimed to elucidate the mechanisms through which a high-fat diet (HFD) induces insulin resistance and insulin hypersecretion by focusing on the effects on enteroendocrine cells, especially those secreting glucose-dependent insulinotropic polypeptide (GIP).

Methods: Forty male Wistar rats, 4 months old, were randomised into two groups; one group received a chow diet and the other one received a purified tripalmitin-based HFD ad libitum.

Analysis of insulin sensitivity in adipose tissue of patients with primary aldosteronism.

Objective: The objective of the study was to assess the effect of high aldosterone levels on insulin sensitivity of adipose tissue in humans.

Methods: Visceral adipose tissue (VAT) was obtained from patients with aldosterone-producing adenoma (APA; n=14) and, as controls, nonfunctioning adenoma (NFA; n=14) undergoing laparoscopic adrenalectomy. Homeostasis model assessment index was higher and potassium was lower in APA than NFA (P<0.

Lipoatrophy induced by subcutaneous insulin infusion: ultrastructural analysis and gene expression profiling.

Context And Objective: Subcutaneous adipose tissue (SAT) lipoatrophy (LA) is a rare complication of insulin therapy. We aimed to analyze the ultrastructural and molecular aspects of LA lesions.

Setting And Patients: Macroscopic and microscopic morphology of SAT beneath the LA areas from patients with type 1 diabetes treated with Lispro insulin by continuous sc insulin infusion was studied using magnetic resonance imaging, immunohistochemistry, electron microscopy, and quantitative PCR for adipose tissue-specific genes.

Evidence for osteocalcin production by adipose tissue and its role in human metabolism.

Context: The adipose tissue (AT), which is an endocrine organ, is linked to several metabolic abnormalities. Undercarboxylated osteocalcin (ucOCN) regulates insulin and adiponectin secretion.

Objective: Our objective was to investigate the involvement of OCN in obesity and to evaluate, in vitro and ex vivo, the role of AT in the modulation of this endocrine circuit.

A structure-activity study to identify novel and efficient substrates of the human semicarbazide-sensitive amine oxidase/VAP-1 enzyme.

Kinetic studies were performed with various alkanamines as "substrate probes" of the properties of the active site of the human semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1). We found that the enzyme-substrate recognition step is mainly controlled by apolar interactions and that a "good" substrate has a molecular structure containing a long aliphatic chain and a second positive charge at a distance greater than 12 A from the reactive amino group. In this context, we identified a novel substrate for the human SSAO/VAP-1, 1,12-diaminododecane (DIADO), which is characterised by the highest catalytic efficiency reported to date in comparison to the prototypic substrate benzylamine.

Increased adipogenic conversion of muscle satellite cells in obese Zucker rats.

Aims/hypothesis: Visceral and intermuscular adipose tissue (IMAT) depots account for most obesity-related metabolic and cardiovascular complications. Muscle satellite cells (SCs) are mesenchymal stem cells giving rise to myotubes and also to adipocytes, suggesting their possible contribution to IMAT origin and expansion. We investigated the myogenic differentiation of SCs and the adipogenic potential of both preadipocytes and SCs from genetically obese Zucker rats (fa/fa), focusing on the role of Wnt signaling in these differentiation processes.

Insulin resistance, adipose depots and gut: interactions and pathological implications.

This review article focuses on the many metabolic actions of insulin at the level of muscle, liver and adipose tissue. In terms of pathogenetic mechanisms, the condition of insulin resistance is complex, as multiple genetic and environmental factors, among which an increasingly sedentary lifestyle associated with high-fat diet, mutually interact according to variable patterns in time in any given individual. It is well recognized that obesity (in particular abdominal obesity) favours the development of insulin resistance.

Clonal characterization of rat muscle satellite cells: proliferation, metabolism and differentiation define an intrinsic heterogeneity.

Satellite cells (SCs) represent a distinct lineage of myogenic progenitors responsible for the postnatal growth, repair and maintenance of skeletal muscle. Distinguished on the basis of their unique position in mature skeletal muscle, SCs were considered unipotent stem cells with the ability of generating a unique specialized phenotype. Subsequently, it was demonstrated in mice that opposite differentiation towards osteogenic and adipogenic pathways was also possible.

Pancreatic acellular matrix supports islet survival and function in a synthetic tubular device: in vitro and in vivo studies.

Increasing pancreatic islet survival and function is a starting point for obtaining a valuable bioartificial pancreas for the treatment of type 1 diabetes. In this context, decellularized matrices, obtained after the removal of tissue cellular part, are known to support in vitro adhesion, growth, and function of several cell types. We demonstrate that a homologous acellular pancreatic matrix is a suitable scaffold for rat islet cultures maintaining their long-term viability and function.

Sleeve gastrectomy as revisional procedure for failed gastric banding or gastroplasty.

Background: Laparoscopic sleeve gastrectomy (LSG) is considered an effective multipurpose operation for morbid obesity, although long-term results are still lacking. Also, the best procedure to be offered in the case of failed restrictive procedures is still debated. We here reported our results of LSG as a revisional procedure for inadequate weight loss and/or complications after adjustable gastric banding or gastroplasty.

Effects of octreotide exposure during pregnancy in acromegaly.

Background: Only six women who were treated with somatostatin analogues (SSAs) throughout their pregnancies have been described so far. The influence of SSAs on the course of pregnancy and newborn outcomes remains largely unknown. Many aspects of SSAs pharmacokinetics in mother and foetus have not yet been defined.

The origin of intermuscular adipose tissue and its pathophysiological implications.

The intermuscular adipose tissue (IMAT) is a depot of adipocytes located between muscle bundles. Several investigations have recently been carried out to define the phenotype, the functional characteristics, and the origin of the adipocytes present in this depot. Among the different mechanisms that could be responsible for the accumulation of fat in this site, the dysdifferentiation of muscle-derived stem cells or other mesenchymal progenitors has been postulated, turning them into cells with an adipocyte phenotype.

The role of the endocannabinoid system in lipogenesis and fatty acid metabolism.

Endocannabinoids (ECs) regulate energy balance by modulating hypothalamic circuits controlling food intake and energy expenditure. However, convincing evidence has accumulated indicating that the EC system is present also in peripheral tissues, in particular in adipose tissue. Fat cells produce and are targets of ECs.