Search

Summary: Objective ANGPTL4 inhibits lipoprotein lipase in adipose tissue, regulating plasma triglycerides levels. In persons with obesity plasma ANGPTL4 levels have been positively correlated with body fat mass, TG levels and low HDL. A loss‐of‐function E40K mutation in ANGPTL4 prevents LPL inhibition, resulting in lower TGs and higher HDLc in the general population. Since obesity determines metabolic alterations and consequently is a major risk factor for cardiovascular disease, the aim was to explore if obesity‐related metabolic abnormalities are modified by the ANGPTL4‐E40K mutation. Methods: ANGPTL4‐E40K was screened in 1206 Italian participants, of which 863 (71.5%) with obesity. All subjects without diabetes underwent OGTT with calculation of indices of insulin‐sensitivity. Results: Participants with obesity carrying the E40K variant had significantly lower TG (p = 0.001) and higher HDLc levels (p = 0.024). Also in the whole population low TGs and high HDLc were confirmed in E40K carriers. In the obese subpopulation it was observed that almost all E40K carriers were within the lowest quartile of TGs (p = 1.1 × 10−9). E40K had no substantial effect of on glucose metabolism. Finally, none of the obese E40K carriers had T2D, and together with the favourable lipid profile, they resemble a metabolically healthy obese (MHO) phenotype, compared to 38% of E40E wild‐type obese that had diabetes and/or dyslipidaemia (p = 0.0106). Conclusions: In participants with obesity the ANGPTL4‐E40K variant protects against dyslipidemia. The phenotype of obese E40K carriers is that of a patient with obesity without metabolic alterations, similar to the phenotype described as metabolic healthy obesity. [ABSTRACT FROM AUTHOR]

Background: Roux-en-Y (RYGB) and one anastomosis gastric bypass (OAGB) represent two of the most used bariatric/metabolic surgery (BMS) procedures. Gut microbiota (GM) shift after bypass surgeries, currently understated, may be a possible key driver for the short- and long-term outcomes., Methods: Prospective, multicenter study enrolling patients with severe obesity, randomized between OAGB or RYGB. Fecal and blood samples were collected, pre- (T0) and 24 months postoperatively (T1). GM was determined by V3-V4 16S rRNA regions sequencing and home-made bioinformatic pipeline based on Qiime2 plugin and R packages., Objects: To compare OAGB vs RYGB microbiota profile at T1 and its impact on metabolic and nutritional status., Results: 54 patients completed the study, 27 for each procedure. An overall significant variation was detected in anthropometric and serum nutritional parameters at T1, with a significant, similar decrease in overall microbial alpha and beta diversity observed in both groups. An increase in relative abundances of Actinobacteria and Proteobacteria and a reduction of Bacteroidetes, no significant changes in Firmicutes and Verrucomicrobia, with an increase of the Firmicutes/Bacteroidetes ratio were observed., Conclusions: BMS promotes a dramatic change in GM composition. This is the first multicenter, RCT evaluating the impact of OAGB vs Roux-en-Y bypass on GM profile. The bypass technique per se did not impact differently on GM or other examined metabolic parameters. The emergence of slightly different GM profile postoperatively may be related to clinical conditions or may influence medium or long-term outcomes and as such GM profile may represent a biomarker for bariatric surgery's outcomes., (© 2024. The Author(s).)

The introduction of the term "Metabolic Steatotic Liver Disease" (MASLD) underscores the critical role of metabolic dysfunction in the development and progression of chronic liver disease and emphasizes the need for strategies that address both liver disease and its metabolic comorbidities. In recent years, a liver-focused perspective has revealed that altered endocrine function of the fatty liver is a key contributor to the metabolic dysregulation observed in MASLD. Due to its secretory capacity, the liver's increased production of proteins known as "hepatokines" has been linked to the development of insulin resistance, explaining why MASLD often precedes dysfunction in other organs and ultimately contributes to systemic metabolic disease. Among these hepatokines, fibroblast growth factor 21 (FGF21) and fetuin-A play central roles in regulating the metabolic abnormalities associated with MASLD, explaining why their dysregulated secretion in response to metabolic stress has been implicated in the metabolic abnormalities of MASLD. This review postulates why their modulation by GLP1-Ras may mediate the beneficial metabolic effects of these drugs, which have increased attention to their emerging role as pharmacotherapy for MASLD. By discussing the crosstalk between GLP1-Ras-FGF21-fetuin-A, this review hypothesizes that the possible modulation of fetuin-A by the novel GLP1-FGF21 dual agonist pharmacotherapy may contribute to the management of metabolic and liver diseases. Although research is needed to go into the details of this crosstalk, this topic may help researchers explore the mechanisms by which this type of pharmacotherapy may manage the metabolic dysfunction of MASLD.

The primary cause of the pandemic scale of type 2 diabetes (T2D) is the excessive and/or abnormal accumulation of adiposity resulting from a chronic positive energy balance. Any form of weight loss dramatically affects the natural history of T2D, favoring prevention, treatment, and even remission in the case of significant weight loss. However, weight regain, which is often accompanied by the recurrence or worsening of obesity complications such as T2D, is an inevitable biological phenomenon that is an integral part of the pathophysiology of obesity. This can occur not only after weight loss, but also during obesity treatment if it is not effective enough to counteract the physiological responses aimed at restoring adiposity to its pre-weight-loss equilibrium state. Over the past few years, many controlled and randomized studies have suggested a superior efficacy of bariatric surgery compared to conventional therapy in terms of weight loss, glycemic control, and rates of T2D remission. Recently, the therapeutic armamentarium in the field of diabetology has been enriched with new antihyperglycemic drugs with considerable efficacy in reducing body weight, which could play a pathogenetic role in the remission of T2D, not through the classical incretin effect, but by improving adipose tissue functions. All these concepts are discussed in this position statement, which aims to deepen the pathogenetic links between obesity and T2D, shift the paradigm from a "simple" interaction between insulin resistance and insulin deficiency, and evaluate the efficacy of different therapeutic interventions to improve T2D management and induce diabetes remission whenever still possible., (© 2024. The Author(s).)

Background: Type 2 diabetes (T2D) is a risk factor for female breast cancer (FBC). Obesity has also been associated with FBC, also depending on menopausal status. This study aimed to evaluate the impact of obesity and T2D on the development, aggressiveness, and invasiveness of FBC., Methods: Demographic, clinical, and histopathological data from 335 women with FBC were collected, and analyzed according to weight category (102 normal weight, 117 overweight, and 116 living with obesity) and the presence/absence of T2D., Results: Age at oncologic diagnosis was not statistically significantly different for body weight; women with overweight or obesity were more likely to have an oncologic diagnosis after menopause than normal weight ( p  < 0.001). The presence of overweight/obesity and T2D seemed to be associated with a higher incidence of metastasis, recurrence, and triple-negative breast cancer (TNBC) subtype ( p  < 0.001). Excess body weight was also associated with high histologic grade (G3) ( p  < 0.005)., Conclusions: These results confirm excess body weight and T2D as unfavorable prognostic factors in terms of the presence of the TNBC subtype, tumor metastasis, recurrence, and aggressiveness (G3 and Ki-67 > 20%). This study highlights the importance of prevention in all women, with early screening, and adequate nutritional programs., Competing Interests: We have no conflicts of interest to disclose., (© 2024 The Author(s). Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Introduction: Patient engagement is essential to achieve long-term goals in obesity management. It is crucial to identify patients' perspectives, misperceptions and unmet educational needs on obesity etiology and treatments, to establish a correct therapeutic alliance between healthcare providers and patients., Methods: Objective: This study, promoted by the regional section of the Italian Obesity Society (SIO Lazio), explores attitudes towards obesity, self-awareness, misperceptions of weight loss strategies, experiences of weight stigma and educational needs of patients living with overweight or obesity. Design and subject: We conducted an anonymous survey among patients who accessed an Obesity Management Centers across the Lazio region of Italy for the first time, from October 2023 to April 2024. Approach: The survey consisted of 27 closed-ended questions grouped into 4 sections: (1) sociodemographic factors and self-reported anthropometric measures; (2) self-awareness and attitudes towards obesity and weight loss strategies; (3) experiences of obesity-related stigma; (4) knowledge and perceptions of obesity treatment options., Results: A total of 300 patients (67.9% women, aged 49.1 ± 14.4 years) returned completed surveys. Despite the self-reported BMI 35.3 ± 7.0 kg/m 2 with three out of four (75.3%) of participants having a BMI ≥ 30 kg/m 2 , only 49% correctly identified themselves as affected by obesity. Almost one-third of the patients believed that obesity does not imply a genetic predisposition (31.9%) and that it is always secondary to psychological or behavioral disorders (29.7%). Interestingly, 66.7% of the patients declared themselves as completely responsible for their own condition and 39.4% considered obesity always treatable by means of lifestyle interventions. Stigma and weight discrimination in healthcare settings were reported by a substantial portion of patients (31.9%). A perception of inadequate support from the National Healthcare System emerged in most of the interviews (61.9%). Most patients (72.1%) felt they were not sufficiently informed about anti-obesity medications and a relevant part of their knowledge was derived from healthcare providers (57.7%) and social networks (19.1%). Weight loss medications were considered useful (63.2%) or necessary (18.4%) by the majority of patients, but only 60.1% would accept without any hesitation a pharmacologic treatment. The main reasons for refusal of pharmacological treatments were the belief that lifestyle intervention is a sufficient treatment (46.9%), the fear of adverse effects (28.1%) and feeling defeated (12.5%). Similarly, for most of participants bariatric surgery is useful (73.3%) or necessary (13.6%)., Conclusion: Despite advancements in obesity research, this study underscores the need to improve patient education and public awareness to optimize the management and treatment of obesity. Addressing misconceptions, stigma, and gaps in knowledge are critical steps towards improving patient outcomes and fostering a supportive healthcare environment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor MW declared a shared affiliation with the authors SM & DC at the time of review. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Colangeli, Russo, Capristo, Mariani, Tuccinardi, Manco, Scipione, Parrotta, Capoccia and Guglielmi.)

Background : Sex differences characterize the prevalence and attitudes toward weight management. Despite limited evidence suggesting greater weight loss in women with anti-obesity pharmacotherapy, sex-specific analysis remains underexplored. This retrospective study aimed to evaluate the sex-specific response to liraglutide 3.0 mg treatment in people with obesity without type 2 diabetes (T2D). Methods : Data were collected from 47 patients (31 women, 16 men) with age > 18 years; BMI ≥ 30 kg/m 2 ; absence of T2D; and exclusion of prior anti-obesity treatment, comorbidities, or bariatric surgery. Only patients who maintained the liraglutide 3.0 mg dose for at least 6 months were included. Results : Both sexes showed significant reductions in weight and BMI at 3 and 6 months. Men achieved greater weight loss (WL), BMI reduction, %WL, WL > 5%, and >10% than women, and they also showed more significant improvements in metabolic parameters (total and LDL cholesterol, Fibrosis-4 Index FIB-4). No significant sex differences were observed in glucose metabolism or renal function. Conclusions : This study showed a greater therapeutic effect of liraglutide 3.0 mg in men. Given men's higher risk of cardiovascular disease (CVD), and underrepresentation in clinical weight loss programs, these findings may increase male engagement and improve their CVD risk.

Background: Primary care providers (PCPs) play an essential role in obesity care as they represent the first contact for patients seeking weight loss interventions., Objective: This study explored the knowledge, experiences, and perceptions of PCPs in the Lazio Region of Italy in the management of obesity., Design and Subjects: We conducted an anonymous survey delivered from March to July 2022 via the newsletter of Rome Provincial Order of Physicians and Dentists and at the annual meeting of the regional section of the Italian Obesity Society., Approach: The survey consisted of 24 closed-ended questions grouped into 5 sections: sociodemographic and work information; assessment of obesity; management of obesity; connections with regional Centres for Obesity Management; attitudes towards obesity., Key Results: A total of 92 PCPs accessed the survey. Of those, 2.2% were excluded because they did not see any patients with obesity. A total of 68 PCPs (75.6%) had complete questionnaires and were included in this analysis. All participants reported asking their patients about their eating habits, lifestyle, and clinical complications at the first assessment. Body weight and blood pressure were measured by 98.5% of participants and 82% calculate body mass index (BMI), while a small proportion of PCPs analysed body composition and fat distribution. Over 80% prescribed laboratory tests and ECG. Approximately 40% of PCPs did not refer patients for nutritional counselling, and most prescribed a low-calorie diet. Sixty-three percent referred patients to an endocrinologist, 48.5% to a psychotherapist, and a minority to specialists for obesity complications. Twenty-three percent prescribed anti-obesity medications and 46.5% referred patients for bariatric surgery only in severe cases. Ninety-one percent stated that obesity is "a complex and multifactorial disease" and 7.4% considered obesity to be secondary to other conditions., Conclusions: Despite most PCPs adopt a correct approach to manage patients with obesity, many aspects could be improved to ensure optimal and multidisciplinary management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer CC declared a shared affiliation with the authors CL, SM, EP to the handling editor at the time of review., (Copyright © 2023 Guglielmi, Capoccia, Russo, Lubrano, Mariani, Poggiogalle, Furia, Alizadeh, Patrizi, Sapienza, Damiani, Tarsitano, Conte and Frontoni.)

Introduction: gut microbiota (GM) seems to be involved in the pathophysiology and progression of both metabolic syndrome (MS) and obesity. The aim was to investigate GM's composition in patients with severe obesity, candidates for bariatric/metabolic surgery BMS., Materials and Methods: Multicentre, prospective, cohort study, enrolling 84 patients with BMI 40-55 kg/m 2 , divided bymetabolic status (MS) inhealthy(group A), pre-MS (B), or MS (C)., Results: No differences were foundregarding anthropometric,nutritional parameters, except for vitamin D.As a whole the alpha and beta diversity examinations showed no statistical differences in GM profile. A total of 5/7 phyla with relative frequencies were identified above 0.1% (Actinobacteria,Bacteroidetes,Firmicutes,Proteobacteria,Verrucomicrobia).FusobacteriaandPatescibacteriarepresented the less abundant. There were no significant differences in the top ten genera.Data onBacteroidetes(inversely related to triglycerides and LDL and directly related to HDL levels) and onFirmicutes(opposite trend) relative abundances suggest no differences among the three conditions.No correlation between the relative abundance of themain phylaand plasmatic glucose levels was observed., Conclusions: In a selected cohort of patients with obesity, MS did not affect the preoperative GM's profile. Severe obesity, per se, seems to be an independent condition affecting GM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Purpose: To evaluate posturography measurements, and their association with other clinical tests used for cervicogenic dizziness diagnosis, in a cohort of subjects suffering from cervicogenic dizziness, compared with healthy subjects., Materials and Methods: Ninety-three cervicogenic dizziness patients and 98 age- and gender-matched healthy subjects underwent video-Head impulse test, posturography testing, evaluation of cervical spine movements by means of cervical range of motion goniometer and self-report and performance measures, including Dizziness Handicap Inventory, Neck Disability Index, Neck Pain Intensity, Tampa Scale for Kinesiophobia and Hospital Anxiety and Depression Scale., Results: Cervicogenic dizziness patients demonstrated significant increases in classical posturography parameters (i.e., surface and length) and in power spectra values within middle and high-frequency interval depicting balance control alterations especially due to proprioceptive integration changes. Furthermore, decreases in degrees of cervical range of motion and increases of self-report and performance measures - highlighting significant complaints of subjective feeling of dizziness - were found in these patients when compared with healthy subjects. Multiple correlations were found between posturography testing and cervical range of motion and Dizziness Handicap Inventory as well as between different self-report and performance measures in cervicogenic dizziness patients., Conclusions: The implementation of posturography - including power spectra analysis - coupled with appropriate exclusion of other disorders, may represent a useful tool in improving cervicogenic dizziness assessment in terms of cost, time consumption and correlation with other measurements.Implications for rehabilitationUncertainties in diagnostic assessment of cervicogenic dizziness reflect doubts regarding the causes underpinning the symptoms of imbalance, unsteadiness, and disorientation.Posturography measurement is a low-cost, time-sparing technique and its implementations have proven to be useful in detecting significant alterations in body sway during perturbating situations.Implementation of power spectra analysis on posturography testing may represent a useful tool in improving cervicogenic dizziness assessment also in terms of rehabilitative treatment follow-up.

Background: Obesity represents a risk factor for COVID-19 infection. Therefore, in order to reduce COVID-19 related comorbidities in obese population a continuation of obesity treatment is needed. However, bariatric procedures were postponed because of COVID-19 restrictions, delaying treatment for obese patients seeking for surgery. This study aimed to test the feasibility of a telematics pre-operative psychological and nutritional assessment as an alternative tool during COVID-19 outbreak., Methods: Twenty-six patients were contacted. The pre-operative assessment consisted in 3-weekly one-to-one online sessions and a final in-person multidisciplinary session. The protocol feasibility has been evaluated on the following outcome: rejection rate (%), dropout rate (%), compliance and satisfaction's degree., Results: Eighteen participants completed the whole protocol and 10% dropped-out. Seventy-two percent of participants obtained an excess weight loss ≥5%. All participants were satisfied of the telematics assessment., Conclusions: COVID-19 emergency has changed standard hospital procedures and this study could represent a landmark for an online pre-operative assessment method to adopt in case of new restrictions.

Aims: Experimental data suggest that visceral adipose tissue (VAT) dysfunction contributes to non-alcoholic fatty liver disease (NAFLD) development in obesity, however, data on humans are limited. Aims of this study were to investigate the relationship between NAFLD and VAT morphofunctional impairment and to determine whether the extent of VAT remodelling is associated with liver damage and metabolic alterations in obesity., Methods: We analysed data from 40 obese individuals candidate to bariatric surgery in whom paired intraoperative liver and omental biopsies were performed for diagnosing NAFLD and VAT inflammation by immunohistochemistry and mRNA expression studies., Results: Within our study population, NAFLD was significantly associated with greater VAT CD68 + macrophages infiltration (P = .04), fibrosis (P = .04) and impaired microvascular density (P = .03) as well as increased expression of markers of local hypoxia, apoptosis and inflammation (UNC5B, CASP7, HIF1-α, IL-8, MIP2, WISP-1, all P < .01). The degree of VAT inflammation correlated with the severity of hepatic injury (steatosis, inflammation, fibrosis; all P < .01) and impaired gluco-metabolic profile., Conclusions: In obese patients, NAFLD is associated in a dose-dependent manner with signs of VAT remodelling, which reflect more severe clinical metabolic impairment. Our study depicts morphological alterations and novel mediators of VAT dysfunction, adding knowledge for future therapeutic approaches to NAFLD and its metabolic complications., (© 2020 John Wiley & Sons Ltd.)

Biliverdin reductase A (BVR-A) is an enzyme involved in the regulation of insulin signalling. Knockout (KO) mice for hepatic BVR-A, on a high-fat diet, develop more severe glucose impairment and hepato-steatosis than the wild type, whereas loss of adipocyte BVR-A is associated with increased visceral adipose tissue (VAT) inflammation and adipocyte size. However, BVR-A expression in human VAT has not been investigated. We evaluated BVR-A mRNA expression levels by real-time PCR in the intra-operative omental biopsy of 38 obese subjects and investigated the association with metabolic impairment, VAT dysfunction, and biopsy-proven non-alcoholic fatty liver disease (NAFLD). Individuals with lower VAT BVR-A mRNA levels had significantly greater VAT IL-8 and Caspase 3 expression than those with higher BVR-A. Lower VAT BVR-A mRNA levels were associated with an increased adipocytes' size. An association between lower VAT BVR-A expression and higher plasma gamma-glutamyl transpeptidase was also observed. Reduced VAT BVR-A was associated with NAFLD with an odds ratio of 1.38 (95% confidence interval: 1.02-1.9; χ 2 test) and with AUROC = 0.89 ( p = 0.002, 95% CI = 0.76-1.0). In conclusion, reduced BVR-A expression in omental adipose tissue is associated with VAT dysfunction and NAFLD, suggesting a possible involvement of BVR-A in the regulation of VAT homeostasis in presence of obesity.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and an independent risk factor for cardiovascular mortality. Angiopoietin-like proteins (ANGPTLs) are targets for vitamin D receptor (VDR)-mediated gene transcription and this axis may promote NAFLD. ANGPTL3 is a hepatokine which inhibits lipoprotein lipase and its experimentally induced inactivation reduces hepatosteatosis. Little is known on ANGPTL3 in human NAFLD and no data exist on its relationship with hepatic VDR/VD-related genes. The aim of this research was to investigate hepatic ANGPTLs and VDR/VD-related gene expression in human obesity in relation to NAFLD., Methods: We conducted a cross-sectional investigation on forty obese subjects with/without NAFLD. We evaluated hepatic ANGPTL3, ANGPTL4, ANGPTL8, LPL, VDR, CYP27A1 and CYP2R1 mRNA expression in liver biopsies by RT-PCR; VDR expression was further investigated by immunohistochemistry; circulating ANGPTL3 was measured by Milliplex assay., Results: Compared to non-NAFLD, NAFLD individuals had significantly higher hepatic VDR, ANGPTL3 and LPL expression. ANGPTL3 correlated with steatosis grade, LPL, VDR, CYP27A1 and CYP2R1 expression. Plasma ANGPTL3 concentrations were positively associated with clinical/histological markers of NAFLD/NASH and with hepatic ANGPTL3 expression. Greater hepatic VDR expression was the main determinant of hepatic ANGPTL3 after adjusting for multiple confounders., Conclusions: Hepatic ANGPTL3 expression correlates with greater VDR expression, presence and severity of NAFLD and translates in increased circulating ANGPTL3, likely as a result of its modulation by up-regulated hepatic VDR in NAFLD. This study provides novel insights to potential mechanisms underlying ANGPTLs-mediated ectopic fat accumulation and NAFLD development in obesity., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Purpose: This pilot project describes the development and implementation of two specialised aviation-style checklist designs for a low-frequency high-risk patient population in a cardiac intensive care unit. The effect of the checklist design as well as the implementation strategies on patient outcomes and adherence to best practice guidelines were also explored. The long-term objective was to improve adherence to accepted processes of care by establishing the checklists as standard practice thereby improving patient safety and outcomes., Methods: During this project, 10specialised crisis checklists using two specific aviation-style designs were developed. A quasiexperimental prospective pre-post repeated measure design including surveys along with repetitive simulations were used to evaluate self-confidence and self-efficacy over time as well as the perceived utility, ease of use, fit into workflow and benefits of the checklists use to patients. Performance, patient outcomes and manikin outcomes were also used to evaluate the effectiveness of the crisis checklists on provider behaviours and patient outcomes., Results: Overall self-confidence and self-confidence related to skills and knowledge while not significant demonstrated clinically relevant improvements that were sustained over time. Perceptions of the checklists were positive with consistent utilisation sustained over time. More importantly, use of the checklists demonstrated a reduction in errors both in the simulated and clinical setting., Conclusion: Recommendations from this study consist of key considerations for development and implementation of checklists including: utilisation of stakeholders in the development phase; implementation in real and simulated environments; and ongoing reinforcement and training to sustain use., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)