Gabriella Garruti

Low dehydroepiandrosterone circulating levels in premenopausal obese women with very high body mass index

Dehydroepiandrosterone (DHEA) has an anti-obesity effect in rodents and reduces body fat in normal men. Therefore, the plasma levels of DHEA were evaluated in nine premenopausal healthy women and in 13 menstrually active nondiabetic obese women, including patients (n = 6) with body mass index (BMI) over 40. In the obese group, a significant inverse correlation between DHEA levels and BMI was found. These results suggest that patients with severe obesity are unable to increase the DHEA adrenal production rate in order to parallel the increase in the hormone metabolic clearance rate (due to enlargement of body fat mass per se). The deficiency of this mechanism might itself contribute to the progressive fat accumulation in severe obesity.

GnRH agonist versus GnRH antagonist in in vitro fertilization and embryo transfer (IVF/ET)

Several protocols are actually available for in Vitro Fertilization and Embryo Transfer. The review summarizes the main differences and the clinic characteristics of the protocols in use with GnRH agonists and GnRH antagonists by emphasizing the major outcomes and hormonal changes associated with each protocol. The majority of randomized clinical trials clearly shows that in “in Vitro” Fertilization and Embryo Transfer, the combination of exogenous Gonadotropin plus a Gonadotropin Releasing Hormone (GnRH) agonist, which is able to suppress pituitary FSH and LH secretion, is associated with increased pregnancy rate as compared with the use of gonadotropins without a GnRH agonist. Protocols with GnRH antagonists are effective in preventing a premature rise of LH and induce a shorter and more cost-effective ovarian stimulation compared to the long agonist protocol. However, a different synchronization of follicular recruitment and growth occurs with GnRH agonists than with GnRH antagonists. Future developments have to be focused on timing of the administration of GnRH antagonists, by giving a great attention to new strategies of stimulation in patients in which radio-chemotherapy cycles are needed.

Obesity and the risk and prognosis of gallstone disease and pancreatitis

Obesity is a risk factor for the formation of cholesterol gallstones and exposes patients to increased risk of gallstone-related complications and cholecystectomy. Rapid weight loss achieved by very low calorie diets or bariatric surgery is also a risk factor for cholelithiasis in obese patients, and therapy should take into account the higher prevalence of gallstones, the possibility of more frequent complications and the need for prophylactic treatment with oral ursodeoxycholic acid during weight loss. Obesity is also frequent in children and adolescents, and the burden of cholesterol cholelithiasis is increasing in this population. The chance to develop acute pancreatitis and the severity of the disease are higher in obese subjects because of specific pathogenic factors, including supersaturated bile and crystal formation, rapid weight loss, and visceral obesity. All health policies aimed at reducing the incidence of obesity worldwide will decrease the incidence of gallstones and gallstone-related complications. The pathophysiological scenarios and the therapeutic implications for obesity, gallstone disease, and pancreatitis are discussed.

Prevention of cholesterol gallstones by inhibiting hepatic biosynthesis and intestinal absorption of cholesterol

Cholesterol cholelithiasis is a multifactorial disease influenced by a complex interaction of genetic and environmental factors and represents a failure of biliary cholesterol homoeostasis in which the physical–chemical balance of cholesterol solubility in bile is disturbed.

The dangerous link between childhood and adulthood predictors of obesity and metabolic syndrome

The purpose of this review is to evaluate whether some risk factors in childhood work as significant predictors of the development of obesity and the metabolic syndrome in adulthood. These factors include exposures to risk factors in the prenatal period, infancy and early childhood, as well as other socio-demographic variables. We searched articles of interest in PubMed using the following terms: ‘predictors AND obesity OR Metabolic syndrome AND (children OR adolescents) AND (dyslipidemia OR type 2 diabetes OR atherosclerosis OR hypertension OR hypercholesterolemia OR cardiovascular disease)’ AND genetic OR epigenetic. Maternal age, smoking and weight gain during pregnancy, parental body mass index, birth weight, childhood growth patterns (early rapid growth and early adiposity rebound), childhood obesity and the parents’ employment have a role in early life. Furthermore, urbanization, unhealthy diets, increasingly sedentary lifestyles and genetic/epigenetic variants play a role in the persistence of obesity in adulthood. Health promotion programs/agencies should consider these factors as reasonable targets to reduce the risk of adult obesity. Moreover, it should be a clinical priority to correctly identify obese children who are already affected by metabolic comorbidities.

Oocyte morphological abnormalities in overweight women undergoing in vitro fertilization cycles

The effect of elevated body mass index (BMI) on the oocyte quality was investigated in women undergoing in vitro fertilization (IVF) cycles. A total of 268 patients classified on the basis of BMI subject to the first reproductive treatment were included in this study: the normal weight (NW) group consisted of 160 patients with BMI 19–24.9 kg/m2 and the overweight (OW) group consisted of 108 patients with BMI ≥25 kg/m2. All women were treated with a standard long luteal protocol. The oocyte features were classified as extracytoplasmic or cytoplasmic abnormalities. Outcomes were oocyte morphology, embryo quality, fertilization and implantation rates, and the ovarian response to stimulation. A higher percentage of oocytes with granular cytoplasm was found in women with BMI ≥25 (p = 0.04). However, percentages of mature, immature oocytes and germinal vesicle were similar in both groups. No differences were found in fertilization and cleavage rates and percentages of embryo quality. The implantation rate (p < 0.001) was significantly lower in the OW group than in the NW group. The amount of gonadotrophins was significantly higher in OW group (p = 0.003). These findings suggest that the poor reproductive outcome of obese women is influenced by the release of ova with reduced fertilization potential.

A Pleiotropic Role for the Orphan Nuclear Receptor Small Heterodimer Partner in Lipid Homeostasis and Metabolic Pathways

Nuclear receptors (NRs) comprise one of the most abundant classes of transcriptional regulators of metabolic diseases and have emerged as promising pharmaceutical targets. Small heterodimer partner (SHP; NR0B2) is a unique orphan NR lacking a DNA-binding domain but contains a putative ligand-binding domain. SHP is a transcriptional regulator affecting multiple key biological functions and metabolic processes including cholesterol, bile acid, and fatty acid metabolism, as well as reproductive biology and glucose-energy homeostasis. About half of all mammalian NRs and several transcriptional coregulators can interact with SHP. The SHP-mediated repression of target transcription factors includes at least three mechanisms including direct interference with the C-terminal activation function 2 (AF2) coactivator domains of NRs, recruitment of corepressors, or direct interaction with the surface of NR/transcription factors. Future research must focus on synthetic ligands acting on SHP as a potential therapeutic target in a series of metabolic abnormalities. Current understanding about the pleiotropic role of SHP is examined in this paper, and principal metabolic aspects connected with SHP function will be also discussed.

Influence of free testosterone on antigen levels of plasminogen activator inhibitor-1 in premonopausal women with central obesity

Women with upper body obesity are at increased risk for cardiovascular disease (CVD). Several studies have demonstrated a reduced fibrinolytic activity in these patients, mainly due to an enhanced activity of plasminogen activator inhibitor-1 (PAI-1). Since an increase of androgenic activity is a feature of central obesity in women, the present study was aimed at evaluating the possibility of a relationship between androgens and PAI-1 (antigen and activity) in 20 premenopausal women, 10 with upper body obesity and 10 controls. In obese women, PAI-1 antigen showed a positive Pearson correlation with free testosterone (FT), insulin, c-peptide, triglycerides (TG), and waist to hip ratio (WHR) (P less than .01), whereas PAI-1 activity correlated positively only with insulin and WHR (P less than .01). In control women, PAI-1 antigen and activity were positively related only to TG (P less than .01). When we applied the multiple regression model with stepwise backward method to our data, both PAI-1 antigen and activity did not maintain any significant association. However, when the data from both the groups were pooled (n = 20), and PAI-1 antigen was considered as the dependent variable, body weight (Sig T = 0.0001), TG (Sig T = 0.0053), FT (Sig T = 0.013), and luteinizing hormone (LH) (Sig T = 0.0474) met the stepwise criteria, suggesting an independent effect of each of these parameters on PAI-1 antigen. On the other hand, when PAI-1 activity was tested as the dependent variable, only body weight maintained a significant relationship with this parameter (Sig T = 0.0006).(ABSTRACT TRUNCATED AT 250 WORDS)

Links between Metabolic Syndrome and Cardiovascular Autonomic Dysfunction

Background. Type 2 diabetes (T2D) might occur within metabolic syndrome (MbS). One of the complications of T2D is an impaired (imp) cardiovascular autonomic function (CAF). Aims. In subjects with T2D and age ≤ 55 years, the prevalence of impCAF and its relationship with BMI, waist, HbA1c values, MbS, hypertension, and family history of T2D and/or hypertension were analysed. Methods. 180 subjects consecutively undergoing a day hospital for T2D were studied. The IDF criteria were used to diagnose MbS. To detect impCAF, 5 tests for the evaluation of CAF were performed with Cardionomic (Meteda, Italy). Univariate and multivariate analyses were performed. Results. The prevalence of impCAF and MbS were 33.9% and 67.8%, respectively. Among diabetics with impCAF, 86.9% had MbS. ImpCAF was significantly associated with MbS, overweight, and HbA1c > 7%. Both logistic (P = 0.0009) and Poisson (P = 0.0113) models showed a positive association between impCAF and MbS. The degree of ImpCAF showed a positive linear correlation with BMI and HbA1c values. Conclusions. The study demonstrates that glycaemic control and overweight influence CAF and that T2D + MbS is more strongly associated with impCAF than isolated T2D. We suggest that MbS not only increases the cardiovascular risk of relatively young subjects with T2D but is also associated with impCAF.

Expression and Secretion of the Atrial Natriuretic Peptide in Human Adipose Tissue and Preadipocytes

Objective: Atrial natriuretic peptide (ANP) is a secretory hormone displaying diuretic, natriuretic, and vasorelaxant activities. Recently, its lipolytic activity has been reported. Since the expression of ANP in adipose tissue has not been documented, we used real‐time reverse transcriptase polymerase chain reaction (RT‐PCR) to investigate the expression of ANP in human adipose tissue and preadipocytes.