F Santini

Università di Pisa, Pisa, Tuscany, Italy

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Publications (123)450.56 Total impact

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    ABSTRACT: Aim of this study was to validate the Comprehensive Appropriateness Scale for the Care of Obesity in Rehabilitation (CASCO-R) and to determine the cut-off score for indicating the most appropriate health care setting for patients with obesity.
    Annali di igiene: medicina preventiva e di comunità 05/2014; 26(3):195-204.
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    ABSTRACT: Objective: Sulfate conjugation of thyroid hormones is an alternate metabolic pathway that facilitates the biliary and urinary excretion of iodothyronines and enhances their deiodination rate, leading to the generation of inactive metabolites. A de-sulfating pathway reverses this process and thyromimetic effects have been observed following the parenteral administration of 3,5,3'-triiodothyronine sulfate (T3S) in rats. The present study investigated whether T3S is absorbed after oral administration in humans and if it represents a source of 3,5,3'-triiodothyronine (T3).Methods: Twenty-eight hypothyroid patients (7 men and 21 women, mean age ± SD = 44 ± 11 years) who had a thyroidectomy for thyroid carcinoma were enrolled. Replacement thyroid hormone therapy was withdrawn (42 days for thyroxine, 14 days for T3) prior to radioiodine remnant ablation. A single oral dose of 20, 40, 80 (4 patients/group) or 160 μg (16 patients/group) T3S was administered 3 days before the planned administration of 131I. Blood samples for serum T3S and total T3 (TT3) concentrations were obtained at various times up to 48 hours after T3S administration.Results: At all T3S doses, serum T3S concentrations increased reaching a peak at 2-4 hours and progressively returned to basal levels within 8 to 24 h. The T3S Cmax and area under the curve (AUC0-48h) were directly and significantly related to the administered dose.An increase in serum TT3 concentration levels was observed, significant after 1 hour, further increased at 2 and 4 hours, and then remained steady up to 48 hours after T3S administration. There was a significant direct correlation between the TT3 AUC0-48h and the administered dose of T3S. No changes in serum free thyroxine (FT4) concentrations during the entire study period were observed, while serum TSH levels increased slightly at 48 hours not related to the dose of administered T3S. No adverse events were reported.Conclusions: 1) T3S is absorbed following oral administration in hypothyroid humans; 2) the oral administration of a single dose of T3S is converted to T3 in a dose-dependent manner and results in steady state serum T3 concentrations for 48 hours; 3) T3S may represent a new agent in combination with thyroxine (T4) in the therapy of hypothyroidism, if similar conversion of T3S to T3 can be demonstrated in euthyroid patients who are already taking T4.
    Endocrine Practice 02/2014; · 2.49 Impact Factor
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    ABSTRACT: Objective Progressive lipodystrophy is one of the major features of the rare MDPL syndrome. Until now, 9 patients affected by this syndrome have been described and a recent study identified in 4 of them an in-frame deletion (Ser605del) of a single codon in the POLD1 gene. Sequence alterations of the POLD1 gene at different sites have been previously reported in human colorectal and endometrial carcinomas. Materials/Methods A 48-year-old woman was admitted to our Department for the assessment of a previously diagnosed lipodystrophy. She did not report a family history of diabetes or other metabolic disorders. Hypertriglyceridemia was diagnosed incidentally when she was 25 years old. At that time she was also diagnosed with sensorineural bilateral hearing loss. At physical examination she presented lipoatrophy affecting nearly the entire body, mandibular hypoplasia, bird-like face, beaked nose, progeroid facial features, with crowded teeth, small mouth and uvula. Abdominal ultrasound showed hepatomegaly and hepatosteatosis. Fat Mass Index measured with DXA was 4.59 Kg/m2, indicating a fat deficit; the oral glucose tolerance test showed an impaired glucose tolerance. Results Sequence analysis of the entire coding region of the POLD1 gene, disclosed a novel heterozygous mutation in exon 13 (R507C). Conclusion The MDPL patient herein described harbors a novel mutation in the exonuclease domain of POLD1. This new variant provides further evidence for a role of POLD1 in the pathogenesis of MDPL. The mechanisms that link changes at various sites of the protein with different diseases remain to be clarified.
    Metabolism. 01/2014;
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    ABSTRACT: Oxidative stress (OS) plays a major role on tissue function. Several catabolic or stress conditions exacerbate OS, inducing organ deterioration. Haptoglobin (Hp) is a circulating acute phase protein, produced by liver and adipose tissue, and has an important anti-oxidant function. Hp is induced in pro-oxidative conditions such as systemic inflammation or obesity. The role of systemic factors that modulate oxidative stress inside muscle cells is still poorly investigated.
    PLoS ONE 01/2014; 9(6):e100745. · 3.73 Impact Factor
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    ABSTRACT: Serotonin (5-HT) is a well-known modulator of eating behavior. However, the molecular mechanisms linking its action to body weight balance have been only partially elucidated. Since platelets are a suitable peripheral model to study 5-HT transport, metabolism and release, we herein evaluated the expression of the platelet 5-HT re-uptake system (SERT) by [3H]-paroxetine binding assay. A cohort of 114 unrelated individuals (34 males, 80 females; age, mean +/- SD: 38.57 +/- 12.47 years) without major psychiatric disorders, was recruited following a naturalistic design regarding age or gender and classified accordingly to their body mass index (BMI). Subjects were divided into 5 groups: normal-weight (NW), overweight (OW) and grade I-III obese (OB) individuals. For gender analyses, data were transformed into [3H]-paroxetine density (Bmax)/BMI ratios to overcome both the disparity of women vs. men number and anthropometric differences between sexes. [3H]-paroxetine Bmax (SERT density, fmol/mg proteins) was reduced in platelet membranes of grade II (p < 0.01) and III (p < 0.001) obese subjects vs. controls and in overweight subjects (p < 0.05) vs. grade III obese individuals. Considering all patients together, a strong negative correlation between Bmax and BMI (r = -0.449; P < 0.0001) was demonstrated. Conversely, [3H]-paroxetine KD (dissociation constant, nM) did not differ among groups. No gender-related variation concerning Bmax/BMI ratios was observed in this cohort of subjects. The down-regulation of SERT in platelet membranes of severe human obesity (BMI > 35 Kg/m2) confirms the involvement of 5-HT system in body weight gain. Moreover, this findings may help to elucidate those monoamine-endocrine networks acting on fat storage, adipocyte signaling and energy balance. Targeting 5-HT/5-HT-related markers will possibly uncover the existence of human obesity subtypes.
    BMC Neuroscience 10/2013; 14(1):128. · 3.00 Impact Factor
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    ABSTRACT: Background: GPR7, the endogenous coupled receptor for neuropeptide B and neuropeptide W, is expressed in several regions of the Central Nervous System (CNS), which are involved in the regulation of feeding behaviour. GPR7 affects the regulation of energy balance through a mechanism independent of leptin and melanocortin pathways. Aim: Aim of this study was to investigate whether GPR7 gene mutations can be detected in human subjects and, in that event, if they are differently distributed among lean and obese subjects. Subjects and Methods: The coding region of GPR7 were sequenced in 150 obese patients and 100 normal-weight unrelated controls. Functional studies of the allelic variants were performed. Results: One genetic GPR7 variant was found (Tyr135Phe - rs33977775) in obese subjects (13,3%) and lean control (25%). Functional studies did not reveal significant differences between the wild type and the Tyr135Phe allelic variants in their NPW mediated capacity to inhibit forskolin-induced cAMP production. Conclusions: Screening of GPR7 gene mutations among lean and obese subjects revealed a Tyr135Phe allelic variant that was fairly common in the study population. As indicated by in vitro and in silico studies, this variant is unlikely to cause a functional derangement of the receptor.
    Journal of endocrinological investigation 04/2013; · 1.65 Impact Factor
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    ABSTRACT: Background:Short sleep and weight gain are inversely related. Sleep deprivation acutely increases food intake but little is known about eating behavior in chronically sleep-deprived, obese individuals.Objective:To characterize the relationship between sleep, food intake and alcohol consumption under free-living conditions in obese, chronically sleep-deprived individuals.Design:Cross-sectional study of a cohort of obese men and premenopausal women.Subjects:A total of 118 obese subjects (age: 40.3±6.7 years; 91 females/27 males; body mass index 38.7±6.4 kg m(-2)).Measurements:Energy, macronutrient, alcohol and caffeine intake assessed by 3-day food records. Sleep duration estimated by actigraphy. Respiratory disturbance index assessed by a portable device.Results:Subjects slept 360.7±50.2 min per night and had a total energy intake of 2279.1±689 kcal per day. Sleep duration and energy intake were inversely related (r=-0.230, P=0.015). By extrapolation, each 30-min deficit per day in sleep duration would translate to an ∼83 kcal per day increase in energy intake. In addition, sleep apnea was associated with a shift from carbohydrate to fat intake. Alcohol intake in subjects consuming >3.5 g of alcohol per day (N=41) was inversely related to sleep duration (r=-0.472, P=0.002).Conclusions:Shorter sleep duration and obstructive sleep apnea are associated with higher energy, fat and alcohol intakes in obese individuals. The importance of this study relies on the population studied, obese subjects with chronic sleep deprivation. These novel findings apply to the large segment of the US population who are obese and sleep-deprived.
    Nutr Diabetes. 01/2013;
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    ABSTRACT: Mutations in the coding sequence of the X-linked gene MeCP2 (Methyl CpG-binding protein) are present in around 80% of patients with Rett Syndrome, a common cause of intellectual disability in female and to date without any effective pharmacological treatment. A relevant, and so far unexplored feature of RTT patients, is a marked reduction in peripheral circulation. To investigate the relationship between loss of MeCP2 and this clinical aspect, we used the MeCP2 null mouse model B6.129SF1-MeCP2tm1Jae for functional and pharmacological studies. Functional experiments were performed on isolated resistance mesenteric vessels, mounted on a pressurized myograph. Vessels from female MeCP2(+/-) mice show a reduced endothelium-dependent relaxation, due to a reduced Nitric Oxide (NO) availability secondary to an increased Reactive Oxygen Species (ROS) generation. Such functional aspects are associated with an intravascular increase in superoxide anion production, and a decreased vascular eNOS expression. These alterations are reversed by curcumin administration (5% (w/w) dietary curcumin for 21 days), which restores endothelial NO availability, decreases intravascular ROS production and normalizes vascular eNOS gene expression. In conclusion our findings highlight alterations in the vascular/endothelial system in the absence of a correct function of MeCP2, and uncover related cellular/molecular mechanisms that are rescued by an anti-oxidant treatment.
    PLoS ONE 01/2013; 8(5):e64863. · 3.73 Impact Factor
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    ABSTRACT: The prevalence of severe obesity, defined as body mass index (BMI) ≥35.0 kg/m(2), is rising rapidly. Given the disproportionately high health burden and healthcare costs associated with this condition, understanding the underlying aetiology, including predisposing genetic factors, is a biomedical research priority. Previous studies have suggested that severe obesity represents an extreme tail of the population BMI variation, reflecting shared genetic factors operating across the spectrum. Here, we sought to determine whether a panel of 32 known common obesity-susceptibility variants contribute to severe obesity in patients (n = 1,003, mean BMI 48.4±8.1 kg/m(2)) attending bariatric surgery clinics in two European centres. We examined the effects of these 32 common variants on obesity risk and BMI, both as individual markers and in combination as a genetic risk score, in a comparison with normal-weight controls (n = 1,809, BMI 18.0-24.9 kg/m(2)); an approach which, to our knowledge, has not been previously undertaken in the setting of a bariatric clinic. We found strong associations with severe obesity for SNP rs9939609 within the FTO gene (P = 9.3×10(-8)) and SNP rs2815752 near the NEGR1 gene (P = 3.6×10(-4)), and directionally consistent nominal associations (P<0.05) for 12 other SNPs. The genetic risk score associated with severe obesity (P = 8.3×10(-11)) but, within the bariatric cohort, this score did not associate with BMI itself (P = 0.264). Our results show significant effects of individual BMI-associated common variants within a relatively small sample size of bariatric patients. Furthermore, the burden of such low-penetrant risk alleles contributes to severe obesity in this population. Our findings support that severe obesity observed in bariatric patients represents an extreme tail of the population BMI variation. Moreover, future genetic studies focused on bariatric patients may provide valuable insights into the pathogenesis of obesity at a population level.
    PLoS ONE 01/2013; 8(8):e70735. · 3.73 Impact Factor
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    ABSTRACT: Background:Short sleep and weight gain are inversely related. Sleep deprivation acutely increases food intake but little is known about eating behavior in chronically sleep-deprived, obese individuals.Objective:To characterize the relationship between sleep, food intake and alcohol consumption under free-living conditions in obese, chronically sleep-deprived individuals.Design:Cross-sectional study of a cohort of obese men and premenopausal women.Subjects:A total of 118 obese subjects (age: 40.3±6.7 years; 91 females/27 males; body mass index 38.7±6.4 kg m(-2)).Measurements:Energy, macronutrient, alcohol and caffeine intake assessed by 3-day food records. Sleep duration estimated by actigraphy. Respiratory disturbance index assessed by a portable device.Results:Subjects slept 360.7±50.2 min per night and had a total energy intake of 2279.1±689 kcal per day. Sleep duration and energy intake were inversely related (r=-0.230, P=0.015). By extrapolation, each 30-min deficit per day in sleep duration would translate to an ∼83 kcal per day increase in energy intake. In addition, sleep apnea was associated with a shift from carbohydrate to fat intake. Alcohol intake in subjects consuming >3.5 g of alcohol per day (N=41) was inversely related to sleep duration (r=-0.472, P=0.002).Conclusions:Shorter sleep duration and obstructive sleep apnea are associated with higher energy, fat and alcohol intakes in obese individuals. The importance of this study relies on the population studied, obese subjects with chronic sleep deprivation. These novel findings apply to the large segment of the US population who are obese and sleep-deprived.
    Nutrition & Diabetes 01/2013; 3:e58.
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    ABSTRACT: Haptoglobin (Hp) is an inflammatory and adiposity marker, its expression during obesity being specifically induced in the white adipose tissue (WAT). We previously reported that when challenged with a high fat diet (HFD) Hp(-/-) mice are partially protected from the onset of insulin resistance and hepatosteatosis. The aim of the present study was to get further insights into Hp function in WAT. To this end, we performed histological and gene expression analysis of the Hp(-/-) WAT, both in standard and obesity conditions, and investigated how Hp deficiency impacts adipogenesis and WAT development. The average size and percentage of very large adipocytes were respectively smaller and reduced in HFD Hp(-/-) mice as compared with HFD WT. The expression of perilipin, HSL and angiogenesis related markers were increased in HFD Hp(-/-) mice. Lean adult Hp(-/-) showed significantly larger adipocytes and lower subcutaneous WAT expression of aP2 and LPL with respect to WT. Hp(-/-) young mice (P30) were characterized by larger adipocyte size and lower expression of adipocyte and adipogenesis markers. Comparison of adipocyte size distribution between young and adult mice revealed attenuated changes in Hp(-/-) mice compared with WT. Mouse embryonic fibroblasts from Hp(-/-) mice were less capable of accumulating triglycerides and exhibited lower expression of PPARγ, aP2, FAS, LPL and Leptin. In conclusion, Hp deficiency tends to blunt the effect of age and diet on the size of adipocytes, which show less susceptibility to develop hypertrophy during obesity and a reduced adipogenic/hyperplastic potential during youth. In addition, Hp deficiency impacts negatively on adipogenesis.
    Adipocyte. 07/2012; 1(3):142-183.
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    ABSTRACT: Obesity is associated with abnormalities of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis. The role of serum IGF-1 measurement for recognition of hypothalamic-pituitary diseases in obesity is still a matter of debate. This study evaluated the serum levels of IGF-1 in a population of severely obese women before and after long-term weight loss obtained by laparoscopic adjustable gastric banding (LAGB). Eighty obese women with body mass index (BMI) of more than 34 kg/m(2) and 80 unrelated age-matched lean controls were enrolled. IGF-1 serum levels were measured together with BMI, liver volume, and intra-abdominal fat thickness assessed by ultrasound. Evaluation was repeated 2 years after LAGB. Our results showed that mean IGF-1 levels in obese subjects before LAGB were significantly lower (p < 0.001) than that observed in age-matched controls. Age and BMI were independent predictors of serum IGF-1 values, overall accounting for 39 % of IGF-1 variability. The mean IGF-1 concentration significantly increased 2 years after LAGB. BMI reduction was independently associated with IGF-1 increase (r = -0.29, p < 0.001). For each point of BMI reduction, the mean increase of serum IGF-1 was 4.39 ng/mL. (1) Severely obese women have low IGF-1 serum levels with respect to normal weight age-matched controls; (2) the extent of IGF-1 deficiency is proportional to increased BMI; (3) after LAGB a spontaneous raise of serum IGF-1 occurs, proportional to the extent of weight reduction; and (4) serum IGF-1 in severely obese subjects may have a limited value for detection of hypothalamic-pituitary diseases.
    Obesity Surgery 05/2012; 22(8):1276-80. · 3.10 Impact Factor
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    ABSTRACT: Obesity is frequently associated with left ventricular hypertrophy (LVH), a condition leading to an increased cardiovascular risk. The objective of this study was to evaluate the prevalence of LVH in a cohort of obese women, with a main focus on the anthropometric and clinical parameters that are associated with an increased left ventricular mass (LVM). The study was performed in 166 obese female patients. LVM was measured by echocardiography. The influence of various parameters on LVM was assessed by multivariate analysis. The prevalence of LVH was drastically different depending on the type of indexed LVM, being 19.9% when the LVM was indexed for body surface area and 72.3% when indexed for height. Age, duration of obesity, weight, waist-to-hip ratio, pulse pressure and hypertension retained an independent direct correlation with the LVM, explaining 39.6% of the overall LVM variability. Among the parameters of the metabolic syndrome, the increase in blood pressure was the main determinant of increased LVM. By using allometric indexation of LVM for height, the results of our study indicate a high prevalence of LVH in a cohort of obese women. Hypertension, pulse pressure, age, duration of obesity, bodyweight and fat distribution, expressed as waist-to-hip ratio, predict 40% of LVM variation.
    High Blood Pressure & Cardiovascular Prevention 03/2012; 19(1):33-9.
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    ABSTRACT: Nonalcoholic fatty liver disease is a common finding in obese subjects. Increasing evidence has been provided suggesting that it represents the hepatic component of the metabolic syndrome. Aim of this longitudinal study was to evaluate the relationships between several anthropometric measures, including the hepatic left lobe volume (HLLV), and various indicators of the metabolic syndrome in a cohort of severely obese women before and after laparoscopic adjustable gastric banding (LAGB). Seventy-five obese women (mean age 45 ± 10 years and body mass index (BMI) 42.5 ± 4.8 kg m(-2)) underwent LAGB and completed an average (± s.d.) post-surgical follow-up of 24 ± 6 months. Determination of HLLV, subcutaneous and intra-abdominal fat (IAF) was based on ultrasound. The principal component statistical analysis applied to pre-operative measurements, highlighted HLLV as a parameter that clustered with serum insulin, IAF, serum glucose and uric acid, along with triglycerides (TGs), alkaline phosphatase and high-density lipoprotein cholesterol. After LAGB, the average reduction of BMI was 23%, 12% for subcutaneous fat (SCF), 42% for HLLV and 40% for visceral fat. Among body weight, BMI, SCF, IAF and HLLV, reduction of the latter was an independent predictor of reduction of serum transaminases and γ-Glutamyltransferase, glucose, insulin and TGs. In severely obese women: (i) HLLV is a sensitive indicator of ectopic fat deposition, clustering with parameters defining the metabolic syndrome; (ii) weight loss achieved by LAGB is associated with a reduction of liver volume as estimated by HLLV; (iii) among various anthropometric parameters measured, reduction of HLLV that follows LAGB represents the best single predictor of improvement of various cardiometabolic risk factors.
    International journal of obesity (2005) 12/2011; 36(3):336-41. · 5.22 Impact Factor
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    ABSTRACT: Leptin is a master regulator of energy homeostasis. Its expression, prevalently localized in adipocytes, is positively related to adipose mass. Epigenetics is emerging as an important contributor to the changes in gene expression undergone by adipose tissue during obesity. We herein investigated the involvement of methylation-dependent mechanisms in leptin regulation in humans. We studied the methylation profile of a 305 bp region in the leptin promoter and analyzed the correspondent leptin expression in visceral adipocyte fraction (AF) and stromal vascular fraction (SVF) of white adipose tissue (WAT) and liver. We found an inverse relationship between methylation and leptin expression with AF displaying a lower methylation density (8%) than SVF and liver (18%, 21%). We evidenced a hot spot region, which mostly differentiates AF versus liver. This includes C15 and 21, which are within the recognition sequences for the transcription factors Sp1 and C/EBP, and C22-23/24, flanking a TATA box. In vitro studies demonstrated that demethylation (by decitabine) increase or de novo activate leptin expression in primary fibroblasts and HeLa cells, respectively. A longitudinal study carried out in patients analyzed before and after bariatric surgery-induced weight loss indicated that in this case decrease in WAT leptin expression (about 50%) does not correspond to changes in promoter methylation density. In conclusion, methylation density in the leptin promoter constitutes one control level for cell type specific leptin expression, whereas weight-loss induced changes in leptin expression does not seem to be methylation-dependent.
    Epigenetics: official journal of the DNA Methylation Society 10/2011; 6(10):1198-206. · 4.58 Impact Factor
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    ABSTRACT: Haptoglobin (Hp) is upregulated in both inflammation and obesity. The low chronic inflammatory state, caused by massive adipose tissue macrophage (ATM) infiltration found in obesity, and low adiponectin have been implicated in the development of insulin resistance and hepatosteatosis. The aim of this work was to investigate whether and how Hp interferes with the onset of obesity-associated complications. Hp-null (Hp(-/-)) and wild-type (WT) mice were metabolically profiled under chow-food diet (CFD) and high-fat diet (HFD) feeding by assessing physical parameters, glucose tolerance, insulin sensitivity, insulin response to glucose load, liver triglyceride content, plasma levels of leptin, insulin, glucose, and adiponectin. ATM content was evaluated by using immunohistochemistry (anti-F4/80 antibody). Adiponectin expression was measured in Hp-treated, cultured 3T3-L1 and human adipocytes. No genotype-related difference was found in CFD animals. HFD-Hp(-/-) mice revealed significantly higher glucose tolerance, insulin sensitivity, glucose-stimulated insulin secretion, and adiponectin expression and reduced hepatomegaly/steatosis compared with HFD-WT mice. White adipose tissue (WAT) of HFD-Hp(-/-) mice showed higher activation of insulin signaling cascade, lower ATM, and higher adiponectin expression. Hp was able to inhibit adiponectin expression in cultured adipocytes. We demonstrated that in the absence of Hp, obesity-associated insulin resistance and hepatosteatosis are attenuated, which is associated with reduced ATM content, increased plasma adiponectin, and higher WAT insulin sensitivity.
    Diabetes 08/2011; 60(10):2496-505. · 7.90 Impact Factor
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    ABSTRACT: The aim of this study was to assess whether small arteries from visceral fat of obese patients show a reduced nitric oxide (NO)-dependent relaxation, as compared with lean control subjects, focusing on the role of the pro-inflammatory cytokine tumor necrosis factor (TNF)-α. Visceral obesity is characterized by endothelial dysfunction. Small arteries from 14 obese (body mass index 48.4 ± 11 kg/m(2)) and 14 control subjects (body mass index 24.9 ± 2 kg/m(2)), dissected after a visceral fat biopsy (laparoscopy), were evaluated on a pressurized micromyograph. Endothelium-dependent relaxation was assessed by acetylcholine. The NO availability, superoxide production, and inflammation were assessed by testing acetylcholine under the nitric oxide synthase (NOS) inhibitor N(ω)-nitro-L-arginine methylester, tempol (superoxide scavenger), and infliximab (monoclonal anti-TNF-α antibody), respectively. The roles of nicotinamide adenine dinucleotide phosphate oxidase and inducible nitric oxide synthase (iNOS) were assessed by their selective inhibitors apocynin and S-methylisothiourea (SMT), respectively. Vascular superoxide generation (dihydroethidium staining) protein expression of TNF-α and NOS isoforms (Western Blot) and TNF-α localization (immunohistochemistry) were assessed. Vessels from obese patients displayed a blunted relaxation to acetylcholine and a reduced inhibitory effect of N(ω)-nitro-L-arginine methylester. These alterations were normalized by tempol or infliximab while being partly ameliorated by apocynin and SMT. Vascular superoxide generation was increased (p < 0.01) in obese patients. This condition was abrogated by both tempol and infliximab and partly (p < 0.05 vs. control subjects) reduced by apocynin or SMT. Enhanced TNF-α and iNOS expression together with increased TNF-α localization in the vascular media were detected. Small arteries from visceral fat of obese patients are characterized by an increased TNF-α production, which reduces NO availability by promoting superoxide generation via nicotinamide adenine dinucleotide phosphate oxidase and iNOS activation.
    Journal of the American College of Cardiology 07/2011; 58(3):238-47. · 14.09 Impact Factor
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    ABSTRACT: A 54-year-old Italian female patient was admitted to our Department with the diagnosis of type 2 diabetes poorly controlled with insulin therapy. The patient was born by consanguineous parents (first degree cousins); she had acromegaloid features, diffuse lipoatrophy and muscular pseudo-hypertrophy since childhood. To confirm the clinical hypothesis of congenital generalized lipodystrophy (CGL) or Berardinelli-Seip syndrome, the sequences of AGPAT2 (encoding for 1-acyl-sn-glycerol-3-phosphate acyltransferase beta) and BSCL2 (encoding for seipin) candidate genes were analyzed. DNA analysis showed the presence of a homozygous mutation in exon 3 of the AGPAT2 gene (P112L). This is the first description of a Caucasian subject with CGL who carries the pathologic allelic variant P112L of the AGPAT2 gene.
    Acta Diabetologica 07/2011; 48(3):243-6. · 4.63 Impact Factor
  • Clinical Chemistry and Laboratory Medicine 05/2011; 49(8):1385-7. · 3.01 Impact Factor

Publication Stats

2k Citations
450.56 Total Impact Points

Institutions

  • 1987–2014
    • Università di Pisa
      • • Department of Clinical and Experimental Medicine
      • • Department of Chemistry and Industrial Chemistry
      Pisa, Tuscany, Italy
  • 2009–2011
    • Dulbecco Telethon Institute
      Dublin, California, United States
  • 2010
    • Scuola Normale Superiore di Pisa
      • Neurobiology Laboratory
      Pisa, Tuscany, Italy
  • 1994–1998
    • Università degli Studi del Sannio
      Benevento, Campania, Italy
  • 1992–1993
    • University of California, Los Angeles
      • Department of Medicine
      Los Angeles, CA, United States