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IntroductionPatient 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.MethodsObjective: 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.ResultsA 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/m2 with three out of four (75.3%) of participants having a BMI ≥ 30 kg/m2, 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%).ConclusionDespite 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.

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.

BackgroundPrimary care providers (PCPs) play an essential role in obesity care as they represent the first contact for patients seeking weight loss interventions.ObjectiveThis study explored the knowledge, experiences, and perceptions of PCPs in the Lazio Region of Italy in the management of obesity.Design and subjectsWe 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.ApproachThe 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 resultsA 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.ConclusionsDespite most PCPs adopt a correct approach to manage patients with obesity, many aspects could be improved to ensure optimal and multidisciplinary management.

IntroductionThe Very Low-Calorie Ketogenic Diet (VLCKD) has emerged as a safe and effective intervention for the management of metabolic disease. Studies examining weight loss predictors are scarce and none has investigated such factors upon VLCKD treatment. Among the molecules involved in energy homeostasis and, more specifically, in metabolic changes induced by ketogenic diets, Fibroblast Growth Factor 21 (FGF21) is a hepatokine with physiology that is still unclear.MethodsWe evaluated the impact of a VLCKD on weight loss and metabolic parameters and assessed weight loss predictors, including FGF21. VLCKD is a severely restricted diet (

Abstract The Fuegians, ancient inhabitants of Tierra del Fuego, are an exemplary case of a cold-adapted population, since they were capable of living in extreme climatic conditions without any adequate clothing. However, the mechanisms of their extraordinary resistance to cold remain enigmatic. Brown adipose tissue (BAT) plays a crucial role in this kind of adaptation, besides having a protective role on the detrimental effect of low temperatures on bone structure. Skeletal remains of 12 adult Fuegians, collected in the second half of XIX century, were analyzed for bone mineral density and structure. We show that, despite the unfavorable climate, bone mineral density of Fuegians was close to that seen in modern humans living in temperate zones. Furthermore, we report significant differences between Fuegians and other cold-adapted populations in the frequency of the Homeobox protein Hox-C4 (HOXC4) rs190771160 variant, a gene involved in BAT differentiation, whose identified variant is predicted to upregulate HOXC4 expression. Greater BAT accumulation might therefore explain the Fuegians extreme cold-resistance and the protection against major cold-related damage. These results increase our understanding of how ecological challenges have been important drivers of human–environment interactions during Humankind history.

Sleep is a vital process essential for survival. The trend of reduction in the time dedicated to sleep has increased in industrialized countries, together with the dramatic increase in the prevalence of obesity and diabetes. Short sleep may increase the risk of obesity, diabetes and cardiovascular disease, and on the other hand, obesity is associated with sleep disorders, such as obstructive apnea disease, insomnia and excessive daytime sleepiness. Sleep and metabolic disorders are linked; therefore, identifying the physiological and molecular pathways involved in sleep regulation and metabolic homeostasis can play a major role in ameliorating the metabolic health of the individual. Approaches aimed at reducing body weight could provide benefits for both cardiometabolic risk and sleep quality, which indirectly, in turn, may determine an amelioration of the cardiometabolic phenotype of individuals. We revised the literature on weight loss and sleep, focusing on the mechanisms and the molecules that may subtend this relationship in humans as in animal models.

Alzheimer’s disease (AD) is a type of dementia whose cause is incompletely defined. Copper (Cu) involvement in AD etiology was confirmed by a meta-analysis on about 6000 participants, showing that Cu levels were decreased in AD brain specimens, while Cu and non-bound ceruloplasmin Cu (non-Cp Cu) levels were increased in serum/plasma samples. Non-Cp Cu was advocated as a stratification add-on biomarker of a Cu subtype of AD (CuAD subtype). To further circumstantiate this concept, we evaluated non-Cp Cu reliability in classifying subtypes of AD based on the characterization of the cognitive profile. The stratification of the AD patients into normal AD (non-Cp Cu ≤ 1.6 µmol/L) and CuAD (non-Cp Cu > 1.6 µmol/L) showed a significant difference in executive function outcomes, even though patients did not differ in disease duration and severity. Among the Cu-AD patients, a 76-year-old woman showed significantly abnormal levels in the Cu panel and underwent whole exome sequencing. The CuAD patient was detected with possessing the homozygous (c.1486T > C; p.(Ter496Argext*19) stop-loss variant in the RGS7 gene (MIM*602517), which encodes for Regulator of G Protein Signaling 7. Non-Cp Cu as an add-on test in the AD diagnostic pathway can provide relevant information about the underlying pathological processes in subtypes of AD and suggest specific therapeutic options.

Morbid obese people are more likely to contract SARS-CoV-2 infection and its most severe complications, as need for mechanical ventilation. Ketogenic Diet (KD) is able to induce a fast weight loss preserving lean mass and is particularly interesting as a preventive measure in obese patients. Moreover, KD has anti-inflammatory and immune-modulating properties, which may help in preventing the cytokine storm in infected patients. Respiratory failure is actually considered a contraindication for VLCKD, a very-low calorie form of KD, but in the literature there are some data reporting beneficial effects on respiratory parameters from ketogenic and low-carbohydrate high-fat diets. KD may be helpful in reducing ventilatory requirements in respiratory patients, so it should be considered in specifically addressed clinical trials as an adjuvant therapy for obese patients infected with SARS-CoV-2.

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.

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.

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.

Background: The research aimed to investigate the incidence of SARS-CoV-2 breakthrough infections and their determinants in a large European cohort of more than 60,000 health workers. Methods: A multicentric retrospective cohort study, involving 12 European centers, was carried out within the ORCHESTRA project, collecting data up to 18 November 2021 on fully vaccinated health workers. The cumulative incidence of SARS-CoV-2 breakthrough infections was investigated with its association with occupational and social–demographic characteristics (age, sex, job title, previous SARS-CoV-2 infection, antibody titer levels, and time from the vaccination course completion). Results: Among 64,172 health workers from 12 European health centers, 797 breakthrough infections were observed (cumulative incidence of 1.2%). The primary analysis using individual data on 8 out of 12 centers showed that age and previous infection significantly modified breakthrough infection rates. In the meta-analysis of aggregated data from all centers, previous SARS-CoV-2 infection and the standardized antibody titer were inversely related to the risk of breakthrough infection (p = 0.008 and p = 0.007, respectively). Conclusion: The inverse correlation of antibody titer with the risk of breakthrough infection supports the evidence that vaccination plays a primary role in infection prevention, especially in health workers. Cellular immunity, previous clinical conditions, and vaccination timing should be further investigated.

Idiopathic Intracranial Hypertension is a neurological disorder primarily affecting overweight women of childbearing age. It is often characterized by radiologic evidence of empty sella (ES), which is in turn frequently associated with pituitary dysfunction, with the somatotropic axis most commonly affected. No recent evidence is available relative to the presence of pituitary hormone deficiencies in adult patients with Idiopathic Intracranial Hypertension (IIH) under pharmacological therapy. We therefore explored pituitary function and morphology in a small cohort of female patients with IIH treated with acetazolamide. Fifteen female patients aged 42 ± 13 years with IIH lasting between 12 and 18 months were evaluated. All patients were affected by recurrent headaches in addition to visual changes of variable severity. IIH diagnosis was made after exclusion of other causes of raised intracranial pressure, and a specific ophthalmological evaluation was conducted to assess for the presence of papilledema. No particular endocrinological disturbances were detected during the enrolment visits, except for a high obesity prevalence (87%, BMI 35.16 ± 8.21 kg/m2), one case of total thyroidectomy for papillary thyroid carcinoma and two patients with irregular menses and mild hirsutism. All the participants underwent a pituitary MRI with contrast, and two different operators performed pituitary measurements in coronal and sagittal scans for morphologic assessment. Blood samples for the anterior pituitary axis evaluation were collected, and the somatotropic axis was further evaluated with a GHRH + Arginine test; other dynamic tests were performed in case of suspected hormonal deficiency. Despite ES being found in 73% of the patients, pituitary volume was preserved, ranging from 213.85 to 642.27mm3 (389.20 ± 125.53mm3); mean coronal pituitary height was 4.53 ± 1.33 mm. Overall, baseline anterior pituitary hormones levels were within normal ranges, and none of the patients with ES had an altered response to the GHRH + arginine stimulation test. We found one patient suffering from iatrogenic hyperthyroidism and two diagnosed with subclinical primary hypothyroidism due to Hashimoto’s thyroiditis. Two young patients were suspected of having polycystic ovary syndrome, and they were therefore further investigated. In conclusion, this case series shows that, despite the high prevalence of ES, the pituitary function of IIH patients treated with acetazolamide is preserved. To date, there is no evidence regarding the trend over time or upon treatment discontinuation in regard to the pituitary function of patients with IIH, and it is therefore not possible to infer whether our finding would be replicable in such settings. We therefore suggest an endocrine follow-up over time in order to monitor for potential pituitary dysfunction.

Chrononutrition is an emerging branch of chronobiology focusing on the profound interactions between biological rhythms and metabolism. This framework suggests that, just like all biological processes, even nutrition follows a circadian pattern. Recent findings elucidated the metabolic roles of circadian clocks in the regulation of both hormone release and the daily feeding–fasting cycle. Apart from serving as energy fuel, ketone bodies play pivotal roles as signaling mediators and drivers of gene transcription, promoting food anticipation and loss of appetite. Herein we provide a comprehensive review of the literature on the effects of the ketogenic diets on biological processes that follow circadian rhythms, among them appetite, sleep, and endocrine function.

Sirtuin1 (SIRT1) and sclerostin play important roles in adipose tissue and bone metabolism. We evaluated the circulating SIRT1 and sclerostin relationship with mass and quality of bone while considering the degree of adiposity. Sixty-six premenopausal women (16 underweight, 25 normal weight and 25 with obesity), aged p = 0.002). When spine BMD, FN BMD and TBS were standardized for BMI, a positive correlation with SIRT1 and a negative correlation with sclerostin were seen (p < 0.005). In the regression analysis, sclerostin was the best independent, negative predictor for BMD and TBS, while SIRT1 directly predicted TBS (p < 0.05). In conclusion, blood measurement of SIRT1 and sclerostin could represent a snapshot of the bone status that, taking into account the degree of adiposity, may reduce the interference of confounding factors in the interpretation of bone health parameters.

The key factors playing a role in the pathogenesis of metabolic alterations observed in many patients with obesity have not been fully characterized. Their identification is crucial, and it would represent a fundamental step towards better management of this urgent public health issue. This aim could be accomplished by exploiting the potential of machine learning (ML) technology. In a single-centre study (n = 2567), we used an ML analysis to cluster patients with metabolically healthy (MHO) or metabolically unhealthy (MUO) obesity, based on several clinical and biochemical variables. The first model provided by ML was able to predict the presence/absence of MHO with an accuracy of 66.67% and 72.15%, respectively, and included the following parameters: HOMA-IR, upper body fat/lower body fat, glycosylated haemoglobin, red blood cells, age, alanine aminotransferase, uric acid, white blood cells, insulin-like growth factor 1 (IGF-1) and gamma-glutamyl transferase. For each of these parameters, ML provided threshold values identifying either MUO or MHO. A second model including IGF-1 zSDS, a surrogate marker of IGF-1 normalized by age and sex, was even more accurate with a 71.84% and 72.3% precision, respectively. Our results demonstrated high IGF-1 levels in MHO patients, thus highlighting a possible role of IGF-1 as a novel metabolic health parameter to effectively predict the development of MUO using ML technology.

Obesity is associated with a poor COVID-19 prognosis, and it seems associated with reduced humoral response to vaccination. Public health campaigns have advocated for weight loss in subjects with obesity, hoping to eliminate this risk. However, no evidence proves that weight loss leads to a better prognosis or a stronger immune response to vaccination. We aimed to investigate the impact of rapid weight loss on the adaptive immune response in subjects with morbid obesity. Twenty-one patients followed a hypocaloric, very-low-carbohydrate diet one week before to one week after the two mRNA vaccine doses. The diet’s safety and efficacy were assessed, and the adaptive humoral (anti-SARS CoV-2 S antibodies, Abs) and cell-mediated responses (IFNγ secretion on stimulation with two different SARS CoV-2 peptide mixes, IFNγ-1 and IFNγ-2) were evaluated. The patients lost ~10% of their body weight with metabolic improvement. A high baseline BMI correlated with a poor immune response (R −0.558, p = 0.013 for IFNγ-1; R −0.581, p = 0.009 for IFNγ-2; R −0.512, p = 0.018 for Abs). Furthermore, there was a correlation between weight loss and higher IFNγ-2 (R 0.471, p = 0.042), and between blood glucose reduction and higher IFNγ-1 (R 0.534, p = 0.019), maintained after weight loss and waist circumference reduction adjustment. Urate reduction correlated with higher Abs (R 0.552, p = 0.033). In conclusion, obesity is associated with a reduced adaptive response to a COVID-19 mRNA vaccine, and weight loss and metabolic improvement may reverse the effect.

Abstract Background To provide indicators for the likelihood of sperm retrieval in patients undergoing testicular sperm extraction is a major issue in the management of male infertility by TESE. The aim of our study was to determine the impact of different parameters, including testicular histopathology, on sperm retrieval in case of reoperation in patients undergoing testicular sperm extraction. Methods We retrospectively analyzed 486 patients who underwent sperm extraction for intracytoplasmic sperm injection and testicular biopsy. Histology was classified into: normal spermatogenesis; hypospermatogenesis (reduction in the number of normal spermatogenetic cells); maturation arrest (absence of the later stages of spermatogenesis); and Sertoli cell only (absence of germ cells). Semen analysis and serum FSH, LH and testosterone were measured. Results Four hundred thirty patients had non obstructive azoospermia, 53 severe oligozoospermia and 3 necrozoospermia. There were 307 (63%) successful sperm retrieval. Higher testicular volume, lower levels of FSH, and better histological features were predictive for sperm retrieval. The same parameters and younger age were predictive factors for shorter time for sperm recovery. After multivariable analysis, younger age, better semen parameters, better histological features and lower values of FSH remained predictive for shorter time for sperm retrieval while better semen and histology remained predictive factors for successful sperm retrieval. The predictive capacity of a score obtained by summing the points assigned for selected predictors (1 point for Sertoli cell only, 0.33 points for azoospermia, 0.004 points for each FSH mIU/ml) gave an area under the ROC curve of 0.843. Conclusions This model can help the practitioner with counseling infertile men by reliably predicting the chance of obtaining spermatozoa with testicular sperm extraction when a repeat attempt is planned.

We report the results of a study on the cumulative incidence of SARS-CoV-2 infections in about 6000 workers of the University Hospital of Modena, Northern Italy, in the period March 2020–January 2021, and the relations with some individual and occupational factors. Overall, in healthcare workers (HCW) the cumulative incidence of COVID-19 during the period was 13.8%. Results confirm the role of overweight and obesity as significant risk factors for SARS-CoV-2 infection. Chronic respiratory diseases, including asthma, also proved to be significantly associated with the infection rate. Considering occupational factors, the COVID-19 risk was about threefold (OR: 2.7; 95% CI 1.7–4.5) greater in nurses and nurse aides than in non-HCW, and about double (OR: 1.9; 95% CI 1.2–3.2) in physicians. Interestingly, an association was also observed between infection risk and nightshifts at work (OR: 1.8; 95% CI 1.4–2.3), significantly related to the total number of shifts in the whole eleven-month period. Even if the vaccination campaign has now greatly modified the scenario of SARS-CoV-2 infections among HCW, the results of this study can be useful for further development of health and policy strategies to mitigate the occupational risk related to the new variants of coronavirus, and therefore the evolution of the pandemic.

Severe obesity is associated with an increased risk of admission to intensive care units and need for invasive mechanical ventilation in patients with COVID-19. The association of obesity and COVID-19 prognosis may be related to many different factors, such as chronic systemic inflammation, the predisposition to severe respiratory conditions and viral infections. The ketogenic diet is an approach that can be extremely effective in reducing body weight and visceral fat in the short term, preserving the lean mass and reducing systemic inflammation. Therefore, it is a precious preventive measure for severely obese people and may be considered as an adjuvant therapy for patients with respiratory compromise.

Nickel (Ni) is a ubiquitous metal, the exposure of which is implied in the development of contact dermatitis (nickel allergic contact dermatitis (Ni-ACD)) and Systemic Ni Allergy Syndrome (SNAS), very common among overweight/obese patients. Preclinical studies have linked Ni exposure to abnormal production/release of Growth Hormone (GH), and we previously found an association between Ni-ACD/SNAS and GH-Insulin-like growth factor 1 (IGF1) axis dysregulation in obese individuals, altogether suggesting a role for this metal as a pituitary disruptor. We herein aimed to directly evaluate the pituitary gland in overweight/obese patients with signs/symptoms suggestive of Ni allergy, exploring the link with GH secretion; 859 subjects with overweight/obesity and suspected of Ni allergy underwent Ni patch tests. Among these, 106 were also suspected of GH deficiency (GHD) and underwent dynamic testing as well as magnetic resonance imaging for routine follow up of benign diseases or following GHD diagnosis. We report that subjects with Ni allergies show a greater GH-IGF1 axis impairment, a higher prevalence of Empty Sella (ES), a reduced pituitary volume and a higher normalized T2 pituitary intensity compared to nonallergic ones. We hypothesize that Ni may be detrimental to the pituitary gland, through increased inflammation, thus contributing to GH-IGF1 axis dysregulation.

Sirtuin 1 (SIRT1) is a sensor of cell energy availability, and with leptin and adiponectin, it regulates metabolic homeostasis. Widely studied in tissues, SIRT1 is under evaluation as a plasmatic marker. We aimed at assessing whether circulating SIRT1 behaves consistently with leptin and adiponectin in conditions of deficiency, excess or normal fat content. Eighty subjects were evaluated: 27 with anorexia nervosa (AN), 26 normal-weight and 27 with obesity. Bloodstream SIRT1, leptin and adiponectin (ELISA), total and trunk fat mass (FM) %, abdominal visceral adipose tissue, liver steatosis and epicardial fat thickness (EFT) were assessed. For each fat store, the coefficient of determination (R2) was used to evaluate the prediction capability of SIRT1, leptin and adiponectin. Plasma SIRT1 and adiponectin coherently decreased with the increase of FM, while the opposite occurred with leptin. Mean levels of each analyte were different between groups (p < 0.005). A significant association between plasma variables and FM depots was observed. SIRT1 showed a good predictive strength for FM, particularly in the obesity group, where the best R2 was recorded for EFT (R2 = 0.7). Blood SIRT1, adiponectin and leptin behave coherently with FM and there is synchrony between them. The association of SIRT1 with FM is substantially superimposable to that of adiponectin and leptin. Given its homeostatic roles, SIRT1 may deserve to be considered as a plasma clinical/biochemical parameter of adiposity and metabolic health.

The use of food supplements for weight loss purposes has rapidly gained popularity as the prevalence of obesity increases. Navigating through the vast, often low quality, literature available is challenging, as is providing informed advice to those asking for it. Herein, we provide a comprehensive literature revision focusing on most currently marketed dietary supplements claimed to favor weight loss, classifying them by their purported mechanism of action. We conclude by proposing a combination of supplements most supported by current evidence, that leverages all mechanisms of action possibly leading to a synergistic effect and greater weight loss in the foreseen absence of adverse events. Further studies will be needed to confirm the weight loss and metabolic improvement that may be obtained through the use of the proposed combination.

Background: Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease. Very low-calorie ketogenic diets (VLCKD) represent a feasible treatment as they induce profound weight loss and insulin resistance (IR) improvement. Despite the recognized benefits on NAFLD deriving from pharmacological administration of fibroblast growth factor 21 (FGF21), whose endogenous counterpart is a marker of liver injury, little is known about its physiology in humans. Aim: To identify predictors of NAFLD improvement as reflected by the reduction of the non-invasive screening tool hepatic steatosis index (HSI) in obese patients undergoing a weight loss program. Methods: Sixty-five obese patients underwent a 90-day dietary program consisting of a VLCKD followed by a hypocaloric low carbohydrate diet (LCD). Anthropometric parameters, body composition, and blood and urine chemistry were assessed. Results: Unlike most parameters improving mainly during the VLCKD, the deepest HSI change was observed after the LCD (p = 0.02 and p < 0.0001, respectively). Baseline HOMA-IR and serum FGF21 were found to be positive (R = 0.414, p = 0009) and negative (R = 0.364, p = 0.04) independent predictors of HSI reduction, respectively. Conclusions: We suggest that patients with IR and NAFLD derive greater benefit from a VLCKD, and we propose a possible role of human FGF21 in mediating NAFLD amelioration following nutritional manipulation.

Very low-calorie ketogenic diets (VLCKD) are an effective and increasingly used tool for weight loss. Traditionally considered high protein, ketogenic diets are often looked at with concern by clinicians due to the potential harm they pose to kidney function. We herein evaluated the efficacy and safety of a VLCKD in patients with obesity and mild kidney failure. A prospective observational real-life study was conducted on ninety-two patients following a VLCKD for approximately 3 months. Thirty-eight had mild kidney failure and fifty-four had no renal condition and were therefore designated as control. Anthropometric parameters, bioelectrical impedance and biochemistry data were collected before and at the end of the dietary intervention. The average weight loss was nearly 20% of initial weight, with a significant reduction in fat mass. We report an improvement of metabolic parameters and no clinically relevant variation regarding liver and kidney function. Upon stratification based on kidney function, no differences in the efficacy and safety outcomes were found. Interestingly, 27.7% of patients with mild renal failure reported normalization of glomerular filtrate after dietary intervention. We conclude that, when conducted under the supervision of healthcare professionals, a VLCKD is an effective and safe treatment for weight loss in patients with obesity, including those affected by mild kidney failure.

Context: Sirtuins (SIRTs) are NAD+-dependent deacetylases, cellular sensors to detect energy availability, and modulate metabolic processes. SIRT1, the most studied family member, influences a number of tissues including adipose tissue. Expression and activity of SIRT1 reduce with weight gain and increase in conditions of starvation.Objective: To focus on SIRT1 plasma concentrations in different conditions of adiposity and to correlate SIRT1 with fat content and distribution, energy homeostasis and inflammation in under-weight, normal-weight, and obese individuals.Materials and Methods: 21 patients with anorexia nervosa, 26 normal-weight and 75 patients with obesity were evaluated. Body fat composition by dual-energy X-ray absorptiometry, ultrasound liver adiposity, echocardiographic epicardial fat thickness (EFT), inflammatory (ESR, CRP, and fibrinogen), and metabolic (FPG, insulin, LDL- and HDL-cholesterol, triglycerides) parameters, calculated basal metabolic rate (BMR) and plasma SIRT1 (ELISA) were measured.Results: SIRT1 was significantly higher in anorexic patients compared to normal-weight and obese patients (3.27 ± 2.98, 2.27 ± 1.13, and 1.36 ± 1.31 ng/ml, respectively). Linear regression models for each predictor variable adjusted for age and sex showed that SIRT1 concentration was inversely and significantly correlated with EFT, fat mass %, liver fat content, BMR, weight, BMI, WC, LDL-cholesterol, insulin, ESR. Stepwise multiple regression analysis revealed that age and EFT were the best independent correlates of SIRT1 (β = −0.026 ± 0.011, p = 0.025, and β = −0.516 ± 0.083, p < 0.001, respectively).Conclusions: Plasma SIRT1 shows a continuous pattern that inversely follows the whole spectrum of adiposity. SIRT1 significantly associates with EFT, a strong index of visceral fat phenotype, better than other indexes of adiposity studied here.

BACKGROUND:A lack of balance between energy intake and expenditure due to overeating or reduced physical activity does not seem to explain entirely the obesity epidemic we are facing, and further factors are therefore being evaluated. Nickel (Ni) is a ubiquitous heavy metal implied in several health conditions. Regarding this, the European Food Safety Authority has recently released an alert on the possible deleterious effects of dietary Ni on human health given the current levels of Ni dietary intake in some countries. Pre-clinical studies have also suggested its role as an endocrine disruptor and have linked its exposure to energy metabolism and glucose homeostasis dysregulation. Ni allergy is common in the general population, but preliminary data suggest it being even more widespread among overweight patients. OBJECTIVES:The aim of this study has been to evaluate the presence of Ni allergy and its association with the metabolic and endocrine profile in overweight and obese individuals. METHODS:We have evaluated 1128 consecutive overweight and obese outpatients. 784 were suspected of being allergic to Ni and 666 were assessed for it. Presence of Ni allergy and correlation with body mass index (BMI), body composition, metabolic parameters and hormonal levels were evaluated. RESULTS:We report that Ni allergy is more frequent in presence of weight excess and is associated with worse metabolic parameters and impaired Growth Hormone secretion. CONCLUSIONS:We confirm that Ni allergy is more common in obese patients, and we report for the first time its association with worse metabolic parameters and impaired function of the GH-IGF1 axis in human subjects.

INTRODUCTION:Recently the association between hepatic steatosis and sarcopenia has been described. GH/IGF-1 axis has been postulated to play a role in linking fatty liver and low muscle mass. The aim of our study was to explore the association between fatty liver index, sarcopenic obesity, insulin sensitivity, and GH/IGF-1 status. METHODS:427 subjects [age: 45.65±13.94 years, BMI: 36.92±6.43 kg/m2] were enrolled. Participants were divided into three groups: fatty liver index (FLI)

There is a widely acknowledged association between insulin resistance and obesity/type 2 diabetes (T2DM), and insulin sensitizing treatments have proved effective in preventing diabetes and inducing weight loss. Obesity and T2DM are also associated with increased inflammation. Mangosteen is a tropical tree, whose fruits—known for their antioxidant properties—have been recently suggested having a possible further role in the treatment of obesity and T2DM. The objective of this pilot study has been to evaluate safety and efficacy of treatment with mangosteen extract on insulin resistance, weight management, and inflammatory status in obese female patients with insulin resistance. Twenty-two patients were randomized 1:1 to behavioral therapy alone or behavioral therapy and mangosteen and 20 completed the 26-week study. The mangosteen group reported a significant improvement in insulin sensitivity (homeostatic model assessment-insulin resistance, HOMA-IR −53.22% vs. −15.23%, p = 0.004), and no side effect attributable to treatment was reported. Given the positive preliminary results we report and the excellent safety profile, we suggest a possible supplementary role of mangosteen extracts in the treatment of obesity, insulin resistance, and inflammation.

BackgroundThe ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG)-detected brown adipose tissue (BAT), is enhanced by cold stimulus and modulated by other factors that still have to be disentangled. We investigated the prevalence, mass, and glucose-uptake activity of ¹⁸F-FDG-detected BAT in a population of adults living in the temperate climatic zone of the Rome area.Methods and findingsWe retrospectively analyzed 6454 patients who underwent ¹⁸F-FDG positron emission tomography/computed tomography (PET/CT) examinations. We found ¹⁸F-FDG BAT in 217 of the 6454 patients (3.36%). Some of them underwent more than one scan and the positive scans were 278 among 8004 (3.47%). The prevalence of patients with at least one positive scan was lower in men (1.77%; 56 of 3161) compared with women (4.88%; 161 of 3293). The BAT positive patients were most frequently younger, thinner and with lower plasma glucose levels compared with BAT negative patients. The amount of BAT in the defined region of interest, the activity of BAT and the number of positive sites of active BAT were similar in both sexes. The prevalence of patients with ¹⁸F-FDG positive PET/CT was highest in December-February, lower in March-May and September-November, and lowest in June-August and was positively correlated with night length and negatively correlated with ambient temperature. Changes in day length and variations of temperature, associated with the prevalence of positive BAT patients. Among the patients who had multiple scans, outdoor temperature was significantly lower and day length was shorter on the occasion when BAT was detected.ConclusionsThis study identifies day length, outdoor temperature, age, sex, BMI, and plasma glucose levels as major determinants of the prevalence, mass, and activity of ¹⁸F-FDG-detected BAT.

Background: Obesity represents a major health hazard, affecting morbidity, psychological status, physical functionality, quality of life, and mortality. The aim of the present study was to explore the differences between metabolically healthy (MHO) and metabolically unhealthy (MUO) obese subjects with regard to physical activity, disability, and health-related quality of life (HR-QoL). Methods: All subjects underwent a multidimensional evaluation, encompassing the assessment of body composition, metabolic biomarkers and inflammation, physical activity level (IPAQ questionnaire), disability (TSD-OC test), and HR-QoL (SF-36 questionnaire). MHO and MUO were defined based on the absence or the presence of the metabolic syndrome, respectively. Results: 253 subjects were included (54 men and 199 women; age: 51.7 ± 12.8 vs. 50.3 ± 11.7 years, p = 0.46; BMI: 38.1 ± 5.7 vs. 38.9 ± 6.7 kg/m2, p = 0.37). No significant difference was observed in body composition. There was no difference between MHO and MUO considering inflammation (hs-CRP: 6517.1 ± 11,409.9 vs. 5294.1 ± 5612.2 g/L; p = 0.37), physical inactivity (IPAQ score below 3000 METs-min/week in 77.6% of MHO vs. 80% of MUO subjects; p = 0.36), obesity-related disability (TSD-OC score > 33%, indicating a high level of obesity-related disability, in 20.2% of MHO vs. 26.5% of MUO subjects; p = 0.28), and the HR-QoL (SF-36 total score: 60 ± 20.8 vs. 62.8 ± 18.2, p = 0.27). Discussion and Conclusion: The metabolic comorbidity and the impairment of functional ability and psycho-social functioning may have a different timing in the natural history of obesity. Alterations in the physical activity level and mobility disabilities may precede the onset of metabolic abnormalities. (Trial registration 2369 prot 166/12—registered 23 February 2012; Amendment 223/14—registered 13 February 2014).

Nonceruloplasmin-bound copper (“free”) is reported to be elevated in Alzheimer's disease (AD). In Wilson's disease (WD) Cu-ATPase 7B protein tightly controls free copper body levels. To explore whether the ATP7B gene harbours susceptibility loci for AD, we screened 180 AD chromosomes for sequence changes in exons 2, 5, 8, 10, 14, and 16, where most of the Mediterranean WD-causing mutations lie. No WD mutation, but sequence changes corresponding to c.1216 T>G Single-Nucleotide Polymorphism (SNP) and c.2495 A>G SNP were found. Thereafter, we genotyped 190 AD patients and 164 controls for these SNPs frequencies estimation. Logistic regression analyses revealed either a trend for the c.1216 SNP (P=.074) or a higher frequency for c.2495 SNP of the GG genotype in patients, increasing the probability of AD by 74% (P=.028). Presence of the GG genotype in ATP7B c.2495 could account for copper dysfunction in AD which has been shown to raise the probability of the disease.

Objective. To verify whether markers of metal homeostasis are related to a magnetoencephalographic index representative of glutamate-mediated excitability of the primary somatosensory cortex. The index is identified as the source strength of the earliest component (M20) of the somatosensory magnetic fields (SEFs) evoked by right median nerve stimulation at wrist. Method. Thirty healthy right-handed subjects (51±22 years) were enrolled in the study. A source reconstruction algorithm was applied to assess the amount of synchronously activated neurons subtending the M20 and the following SEF component (M30), which is generated by two independent contributions of gabaergic and glutamatergic transmission. Serum copper, ceruloplasmin, iron, transferrin, transferrin saturation, and zinc levels were measured. Results. Total copper and ceruloplasmin negatively correlated with the M20 source strength. Conclusion. This pilot study suggests that higher level of body copper reserve, as marked by ceruloplasmin variations, parallels lower cortical glutamatergic responsiveness.