Metabolism Disorders
Phisiopatology and Treatment of Obesity
24
Scopus Publications
Scopus Publications
Oxytocin, Weight Loss and Ketosis in Response to a Very-Low-Calorie Ketogenic Diet: An Exploratory Study Elena Gangitano, Rebecca Rossetti, Rossella Tozzi, Paola Nevi, Davide Masi, et al. Nutrients, 2026 Background/Objectives: Obesity is a chronic relapsing disorder associated with many comorbidities. Some evidence suggests that oxytocin (OT) has an anorexigenic effect, but its levels are often increased in obesity. This study investigates the effects of weight loss induced by a very-low-calorie ketogenic diet (VLCKD) on oxytocin levels. Methods: A total of 47 subjects with overweight or obesity, 28 females (60%) and 19 males, with a mean age of 55.5 ± 7.3 years and mean BMI 35.9 ± 4.4 kg/m2, underwent VLCKD for 45 days. We assessed anthropometric parameters, metabolic profile, body composition and OT levels at baseline (t0) and at the end of the diet (t1). Results: After weight loss, plasma OT levels significantly dropped. Baseline OT correlated with BMI, fat mass and trunk fat. A linear relationship was observed between Delta OT levels and Delta BMI. Baseline OT was an independent predictor of weight loss and directly correlated with blood ketone levels at the end of the study. An optimal serum OT cut-off that predicts ketosis occurrence was identified. Conclusions: Weight loss obtained with a VLCKD reduces OT levels in patients with excess weight. Baseline OT predicts weight loss and correlates with ketone body levels during a VLCKD.
A comparison of the effects of direct oral anticoagulants versus vitamin K antagonists and antiplatelet agents on the timing and outcomes of hip fracture surgery in patients older than 65 years: the ORTHO-GER-DOAC study Emilio Martini, Rossella Tozzi, Giulia Annessi, Laura Borgese, Maria Lia Lunardelli, et al. European Geriatric Medicine, 2025 Introduction The use of direct oral anticoagulants (DOACs) may delay surgery in older hip fracture patients. Aim To assess whether preoperative DOAC activity measurement enables surgery within 48 h in hip fracture patients at a similar prevalence compared to patients receiving other antithrombotics or no antithrombotics. Methods A retrospective observational cohort study of hip fracture patients older than 65 years admitted to three Orthogeriatrics units in Italy from 2015 to 2022 was conducted. At admission, demographical and comorbid conditions were recorded, and antithrombotics were stopped. Patients on vitamin K antagonists (VKAs) underwent international normalized ratio (INR) assessments and received vitamin K to achieve an INR below 1.5. Patients receiving DOACs who were enrolled before 2018 underwent daily drug testing, and surgery was performed only after DOAC levels were near or below trough levels. Hours from hospital admission to surgery, perioperative total blood loss, major bleeding and mortality at 90 days were recorded. Results Amongst the 747 patients (median age 85 years; M/F: 192/555), the prevalence of surgery within 48 h was significantly lower amongst patients receiving DOACs (47%) than amongst patients receiving antiplatelet agents (77%) and patients receiving no antithrombotic agents (73%). Preoperative DOAC measurements significantly delayed the time to surgery (median 51 vs. 42 h: P < 0.05). The major bleeding and mortality rates at 90 days did not differ based on the type of antithrombotics used. The degree of perioperative blood loss was greater in patients receiving DOACs, regardless of drug measurement, than in patients taking other antithrombotics. Conclusions DOAC measurement may delay hip fracture surgery, as even low presurgical levels of DOACs are associated with greater perioperative blood loss.
Does HLA explain the high incidence of childhood-onset type 1 diabetes in the Canary Islands? The role of Asp57 DQB1 molecules Yeray Nóvoa-Medina, Itahisa Marcelino-Rodriguez, Nicolás M. Suárez, Marta Barreiro-Bautista, Eva Rivas-García, et al. BMC Pediatrics, 2024 The Canary Islands inhabitants, a recently admixed population with significant North African genetic influence, has the highest incidence of childhood-onset type 1 diabetes (T1D) in Spain and one of the highest in Europe. HLA accounts for half of the genetic risk of T1D. Aims To characterize the classical HLA-DRB1 and HLA-DQB1 alleles in children from Gran Canaria with and without T1D. Methods We analyzed classic HLA-DRB1 and HLA-DQB1 alleles in childhood-onset T1D patients (n = 309) and control children without T1D (n = 222) from the island of Gran Canaria. We also analyzed the presence or absence of aspartic acid at position 57 in the HLA-DQB1 gene and arginine at position 52 in the HLA-DQA1 gene. Genotyping of classical HLA-DQB1 and HLA-DRB1 alleles was performed at two-digit resolution using Luminex technology. The chi-square test (or Fisher's exact test) and odds ratio (OR) were computed to assess differences in allele and genotype frequencies between patients and controls. Logistic regression analysis was also used. Results Mean age at diagnosis of T1D was 7.4 ± 3.6 years (46% female). Mean age of the controls was 7.6 ± 1.1 years (55% female). DRB1*03 (OR = 4.2; p = 2.13–13), DRB1*04 (OR = 6.6; p ≤ 2.00–16), DRB1* 07 (OR = 0.37; p = 9.73–06), DRB1*11 (OR = 0.17; p = 6.72–09), DRB1*12, DRB1*13 (OR = 0.38; p = 1.21–05), DRB1*14 (OR = 0.0; p = 0.0024), DRB1*15 (OR = 0.13; p = 7.78–07) and DRB1*16 (OR = 0.21; p = 0.003) exhibited significant differences in frequency between groups. Among the DQB1* alleles, DQB1*02 (OR: 2.3; p = 5.13–06), DQB1*03 (OR = 1.7; p = 1.89–03), DQB1*05 (OR = 0.64; p = 0.027) and DQB1*06 (OR = 0.19; p = 6.25–14) exhibited significant differences. A total of 58% of the studied HLA-DQB1 genes in our control population lacked aspartic acid at position 57. Conclusions In this population, the overall distributions of the HLA-DRB1 and HLA-DQB1 alleles are similar to those in other European populations. However, the frequency of the non-Asp-57 HLA-DQB1 molecules is greater than that in other populations with a lower incidence of T1D. Based on genetic, historical and epidemiological data, we propose that a common genetic background might help explain the elevated pediatric T1D incidence in the Canary Islands, North-Africa and middle eastern countries.
SIRT1 Serum Concentrations in Lipodystrophic Syndromes Luisa Salvatori, Silvia Magno, Giovanni Ceccarini, Rossella Tozzi, Savina Contini, et al. International Journal of Molecular Sciences, 2024 Lipodystrophies (LDs) are rare, complex disorders of the adipose tissue characterized by selective fat loss, altered adipokine profile and metabolic impairment. Sirtuins (SIRTs) are class III NAD+-dependent histone deacetylases linked to fat metabolism. SIRT1 plays a critical role in metabolic health by deacetylating target proteins in tissue types including liver, muscle, and adipose. Circulating SIRT1 levels have been found to be reduced in obesity and increased in anorexia nervosa and patients experiencing weight loss. We evaluated circulating SIRT1 levels in relation to fat levels in 32 lipodystrophic patients affected by congenital or acquired LDs compared to non-LD subjects (24 with anorexia nervosa, 22 normal weight, and 24 with obesity). SIRT1 serum levels were higher in LDs than normal weight subjects (mean ± SEM 4.18 ± 0.48 vs. 2.59 ± 0.20 ng/mL) and subjects with obesity (1.7 ± 0.39 ng/mL), whereas they were close to those measured in anorexia nervosa (3.44 ± 0.46 ng/mL). Our findings show that within the LD group, there was no relationship between SIRT1 levels and the amount of body fat. The mechanisms responsible for secretion and regulation of SIRT1 in LD deserve further investigation.
Pituitary T1 signal intensity at magnetic resonance imaging is reduced in patients with obesity: results from the CHIASM study Giulia Puliani, Emilia Sbardella, Alessia Cozzolino, Valentina Sada, Rossella Tozzi, et al. International Journal of Obesity, 2023 Background Despite obesity being well known to be associated with several pituitary hormone imbalances, pituitary appearance in magnetic resonance imaging (MRI) in patients with obesity is understudied. Objective To evaluate the pituitary volume and signal intensity at MRI in patients with obesity. Methods This is a prospective study performed in an endocrine Italian referral center (ClinicalTrial.gov Identifier: NCT03458533). Sixty-nine patients with obesity (BMI > 30 kg/m2) and twenty-five subjects without obesity were enrolled. Thirty-three patients with obesity were re-evaluated after 3 years of diet and lifestyle changes, of whom 17 (51.5%) achieved a > 5% loss of their initial body weight, whereas the remaining 16 (48.5%) had maintained or gained weight. Evaluations included metabolic and hormone assessments, DEXA scan, and pituitary MRI. Pituitary signal intensity was quantified by measuring the pixel density using ImageJ software. Results At baseline, no difference in pituitary volume was observed between the obese and non-obese cohorts. At the 3-year follow-up, pituitary volume was significantly reduced (p = 0.011) only in participants with stable-increased body weight. Furthermore, a significant difference was noted in the mean pituitary intensity of T1-weighted plain and contrast-enhanced sequences between the obese and non-obese cohorts at baseline (p = 0.006; p = 0.002), and a significant decrease in signal intensity was observed in the subgroup of participants who had not lost weight (p = 0.012; p = 0.017). Insulin-like growth factor-1 levels, following correction for BMI, were correlated with pituitary volume (p = 0.001) and intensity (p = 0.049), whereas morning cortisol levels were correlated with pituitary intensity (p = 0.007). The T1-weighted pituitary intensity was negatively correlated with truncal fat (p = 0.006) and fibrinogen (p = 0.018). Conclusions The CHIASM study describes a quantitative reduction in pituitary intensity in T1-weighted sequences in patients with obesity. These alterations could be explained by changes in the pituitary stromal tissue, correlated with low-grade inflammation.
Genome Editing and Obesity Davide Masi, Rossella Tozzi, Mikiko Watanabe Advances in Experimental Medicine and Biology, 2023
Ketogenic Diet Increases Serum and White Adipose Tissue SIRT1 Expression in Mice Rossella Tozzi, Federica Campolo, Enke Baldini, Mary Anna Venneri, Carla Lubrano, et al. International Journal of Molecular Sciences, 2022 Overnutrition and its sequelae have become a global concern due to the increasing incidence of obesity and insulin resistance. A ketogenic diet (KD) is widely used as a dietary treatment for metabolic disorders. Sirtuin1 (SIRT1), a metabolic sensor which regulates fat homeostasis, is modulated by dietary interventions. However, the influence of nutritional ketosis on SIRT1 is still debated. We examined the effect of KD on adipose tissue, liver, and serum levels of SIRT1 in mice. Adult C57BL/6J male mice were randomly assigned to two isocaloric dietary groups and fed with either high-fat KD or normal chow (NC) for 4 weeks. Serum SIRT1, beta-hydroxybutyrate (βHB), glucose, and triglyceride levels, as well as SIRT1 expression in visceral (VAT), subcutaneous (SAT), and brown (BAT) adipose tissues, and in the liver, were measured. KD-fed mice showed an increase in serum βHB in parallel with serum SIRT1 (r = 0.732, p = 0.0156), and increased SIRT1 protein expression in SAT and VAT. SIRT1 levels remained unchanged in BAT and in the liver, which developed steatosis. Normal glycemia and triglycerides were observed. Under a KD, serum and white fat phenotypes show higher SIRT1, suggesting that one of the molecular mechanisms underlying a KD’s potential benefits on metabolic health involves a synergistic interaction with SIRT1.
Ketone Bodies and SIRT1, Synergic Epigenetic Regulators for Metabolic Health: A Narrative Review Rossella Tozzi, Fiammetta Cipriani, Davide Masi, Sabrina Basciani, Mikiko Watanabe, et al. Nutrients, 2022 Ketone bodies (KBs) and Sirtuin-1 (SIRT1) have received increasing attention over the past two decades given their pivotal function in a variety of biological contexts, including transcriptional regulation, cell cycle progression, inflammation, metabolism, neurological and cardiovascular physiology, and cancer. As a consequence, the modulation of KBs and SIRT1 is considered a promising therapeutic option for many diseases. The direct regulation of gene expression can occur in vivo through histone modifications mediated by both SIRT1 and KBs during fasting or low-carbohydrate diets, and dietary metabolites may contribute to epigenetic regulation, leading to greater genomic plasticity. In this review, we provide an updated overview of the epigenetic interactions between KBs and SIRT1, with a particular glance at their central, synergistic roles for metabolic health.
Growth Hormone Secretory Capacity Is Associated with Cardiac Morphology and Function in Overweight and Obese Patients: A Controlled, Cross-Sectional Study Elena Gangitano, Giuseppe Barbaro, Martina Susi, Rebecca Rossetti, Maria Elena Spoltore, et al. Cells, 2022 Obesity is associated with increased cardiovascular morbidity. Adult patients with growth hormone deficiency (GHD) show morpho-functional cardiological alterations. A total of 353 overweight/obese patients are enrolled in the period between 2009 and 2019 to assess the relationships between GH secretory capacity and the metabolic phenotype, cardiovascular risk factors, body composition and cardiac echocardiographic parameters. All patients underwent GHRH + arginine test to evaluate GH secretory capacity, DEXA for body composition assessment and transthoracic echocardiography. Blood samples are also collected for the evaluation of metabolic parameters. In total, 144 patients had GH deficiency and 209 patients had normal GH secretion. In comparing the two groups, we found significant differences in body fat distribution with predominantly visceral adipose tissue accumulation in GHD patients. Metabolic syndrome is more prevalent in the GHD group. In particular, fasting glycemia, triglycerides and systolic and diastolic blood pressure are found to be linearly correlated with GH secretory capacity. Epicardial fat thickness, E/A ratio and indexed ventricular mass are worse in the GHD group. In the population studied, metabolic phenotype, body composition, cardiovascular risk factors and cardiac morphology are found to be related to the GH secretory capacity. GH secretion in the obese patient seems to be an important determinant of metabolic health.
