The interplay between excess weight and hyper-glycemia on NCDs in Italy: results from a cross-sectional study.

PURPOSE: To evaluate the prevalence of chronic comorbidities according to BMI classes and assess the interplay between excess body weight and blood glucose abnormalities in increasing the risk of major chronic diseases. METHODS: The study is based on data from the Health Search/IQVIA Health LPD Longitudinal Patient Database, an Italian general practice registry, with data obtained from electronic clinical records of 800 general practitioners throughout Italy. Data relative to the year 2018 were analyzed. The study population was classified according to BMI (normal weight, overweight, and obesity classes 1, 2 and 3) and glucose metabolism status (normoglycemia-NGT; impaired fasting glucose-IFG; diabetes mellitus-DM). Comorbidities were identified through ICD-9 CM codes. RESULTS: Data relative to 991,917 adults were analyzed. The prevalence of overweight was 39.4%, while the prevalence of obesity was 11.1% (class 1: 7.9%, class 2: 2.3%, class 3: 0.9%). In the whole population, the prevalence of DM and IFG was 8.9% and 4.2%, respectively. Both overweight and obesity were associated with an increasing prevalence of glucose metabolism alterations and a large array of different chronic conditions, including cardio-cerebrovascular diseases, heart failure, chronic kidney disease, osteoarticular diseases, depression, sleep apnea, and neoplasms of the gastrointestinal tract. Within each BMI class, the presence of IFG, and to a greater extent DM, identified subgroups of individuals with a marked increase in the risk of concomitant chronic conditions. CONCLUSION: Addressing the double burden of excess weight and hyperglycemia represents an important challenge and a healthcare priority.

Laparoscopic Sleeve Gastrectomy with Staple-Line Oversewing in a Patient with Factor XI Deficiency: A Case Report.

BACKGROUND Bariatric surgery (BS) has a lower percentage of complications than other abdominal surgeries. Hemorrhage in one of the most common complications and can be life-threatening. Hereditary factor XI (FXI) deficiency is a coagulation disorder that can result in excessive bleeding requiring intervention to restore hemostasis. Risks over benefits in patients with morbid obesity with BS indication, as well as those with FXI deficiency, should be carefully evaluated. This article reports the case of an obese woman with FXI deficiency -undergoing SG. CASE REPORT A 49-year-old woman with a BMI of 51 kg/m² was diagnosed as having severe FXI deficiency during preoperative exams prior to bariatric surgery. Virus-inactivated homo-group plasma 10 ml/kg infusion was administrated 1 h before surgery, during the entire procedure, and continuing until postoperative day (POD) 4. A very low-calorie ketogenic diet (VLCKD) was proposed to the patient 4 weeks before surgery. Laparoscopic sleeve gastrectomy was performed with staple-line reinforcement by oversewing the seromuscular layer using continuous suture. Subcutaneous enoxaparin 4000 U.I. was administered from POD 1 until POD 25 to prevent any thromboembolic event. The patient was discharged on POD 5 in good clinical condition. CONCLUSIONS Risks of bleeding andor thromboembolic events before or after BS are increased in patient with FXI deficiency. Bariatric surgery in these patients is safe in experienced BS centers, and the risks associated with the obesity seem to exceed those of the coagulopathy and surgery. Careful preoperative counseling, extensive hematological checks, and meticulous surgery are essential to reduce BS risks. Sleeve gastrectomy oversewing the stapler line seems a reasonable choice.

Genetics: A Starting Point for the Prevention and the Treatment of Obesity.

Obesity is a common, serious, and costly disease. More than 1 billion people worldwide are obese-650 million adults, 340 million adolescents, and 39 million children. The WHO estimates that, by 2025, approximately 167 million people-adults and children-will become less healthy because they are overweight or obese. Obesity-related conditions include heart disease, stroke, type 2 diabetes, and certain types of cancer. These are among the leading causes of preventable, premature death. The estimated annual medical cost of obesity in the United States was nearly $173 billion in 2019 dollars. Obesity is considered the result of a complex interaction between genes and the environment. Both genes and the environment change in different populations. In fact, the prevalence changes as the result of eating habits, lifestyle, and expression of genes coding for factors involved in the regulation of body weight, food intake, and satiety. Expression of these genes involves different epigenetic processes, such as DNA methylation, histone modification, or non-coding micro-RNA synthesis, as well as variations in the gene sequence, which results in functional alterations. Evolutionary and non-evolutionary (i.e., genetic drift, migration, and founder's effect) factors have shaped the genetic predisposition or protection from obesity in modern human populations. Understanding and knowing the pathogenesis of obesity will lead to prevention and treatment strategies not only for obesity, but also for other related diseases.

The three facets of the SARS-CoV-2 pandemic during the first two waves in the northern, central, and southern Italy.

BACKGROUND: There is a scarcity of information in literature regarding the clinical differences and comorbidities of patients affected by Coronavirus disease 2019 (COVID-19), which could clarify the different prevalence of the outcomes (composite and only death) between several Italian regions. OBJECTIVE: This study aimed to assess the heterogeneity of clinical features of patients with COVID-19 upon hospital admission and disease outcomes in the northern, central, and southern Italian regions. METHODS: An observational cohort multicenter retrospective study including 1210 patients who were admitted for COVID-19 in Infectious diseases, Pulmonology, Endocrinology, Geriatrics and Internal Medicine Units in Italian cities stratified between north (263 patients); center (320 patients); and south (627 patients), during the first and second pandemic waves of SARS-CoV-2 (from February 1, 2020 to January 31, 2021). The data, obtained from clinical charts and collected in a single database, comprehended demographic characteristics, comorbidities, hospital and home pharmacological therapies, oxygen therapy, laboratory values, discharge, death and Intensive care Unit (ICU) transfer. Death or ICU transfer were defined as composite outcomes. RESULTS: Male patients were more frequent in the northern Italian region than in the central and southern regions. Diabetes mellitus, arterial hypertension, chronic pulmonary and chronic kidney diseases were the comorbidities more frequent in the southern region; cancer, heart failure, stroke and atrial fibrillation were more frequent in the central region. The prevalence of the composite outcome was recorded more frequently in the southern region. Multivariable analysis showed a direct association between the combined event and age, ischemic cardiac disease, and chronic kidney disease, in addition to the geographical area. CONCLUSIONS: Statistically significant heterogeneity was observed in patients with COVID-19 characteristics at admission and outcomes from northern to southern Italy. The higher frequency of ICU transfer and death in the southern region may depend on the wider hospital admission of frail patients for the availability of more beds since the burden of COVID-19 on the healthcare system was less intense in southern region. In any case, predictive analysis of clinical outcomes should consider that the geographical differences that may reflect clinical differences in patient characteristics, are also related to access to health-care facilities and care modalities. Overall, the present results caution against generalizability of prognostic scores in COVID-19 patients derived from hospital cohorts in different settings.

Bariatric surgery-induced weight loss and associated genome-wide DNA-methylation alterations in obese individuals.

BACKGROUND: Obesity is a multifactorial and chronic condition of growing universal concern. It has recently been reported that bariatric surgery is a more successful treatment for severe obesity than other noninvasive interventions, resulting in rapid significant weight loss and associated chronic disease remission. The identification of distinct epigenetic patterns in patients who are obese or have metabolic imbalances has suggested a potential role for epigenetic alterations in causal or mediating pathways in the development of obesity-related pathologies. Specific changes in the epigenome (DNA methylome), associated with metabolic disorders, can be detected in the blood. We investigated whether such epigenetic changes are reversible after weight loss using genome-wide DNA methylome analysis of blood samples from individuals with severe obesity (mean BMI ~ 45) undergoing bariatric surgery. RESULTS: Our analysis revealed 41 significant (Bonferroni p < 0.05) and 1169 (false discovery rate p < 0.05) suggestive differentially methylated positions (DMPs) associated with weight loss due to bariatric surgery. Among the 41 significant DMPs, 5 CpGs were replicated in an independent cohort of BMI-discordant monozygotic twins (the heavier twin underwent diet-induced weight loss). The effect sizes of these 5 CpGs were consistent across discovery and replication sets (p < 0.05). We also identified 192 differentially methylated regions (DMRs) among which SMAD6 and PFKFB3 genes were the top hypermethylated and hypomethylated regions, respectively. Pathway enrichment analysis of the DMR-associated genes showed that functional pathways related to immune function and type 1 diabetes were significant. Weight loss due to bariatric surgery also significantly decelerated epigenetic age 12 months after the intervention (mean = - 4.29; p = 0.02). CONCLUSIONS: We identified weight loss-associated DNA-methylation alterations targeting immune and inflammatory gene pathways in blood samples from bariatric-surgery patients. The top hits were replicated in samples from an independent cohort of BMI-discordant monozygotic twins following a hypocaloric diet. Energy restriction and bariatric surgery thus share CpGs that may represent early indicators of response to the metabolic effects of weight loss. The analysis of bariatric surgery-associated DMRs suggests that epigenetic regulation of genes involved in endothelial and adipose tissue function is key in the pathophysiology of obesity.

A multi-marker integrative analysis reveals benefits and risks of bariatric surgery.

Bariatric surgery (BS) is an effective intervention for severe obesity and associated comorbidities. Although several studies have addressed the clinical and metabolic effects of BS, an integrative analysis of the complex body response to surgery is still lacking. We conducted a longitudinal data study with 36 patients with severe obesity who were tested before, 6 and 12 months after restrictive BS for more than one hundred blood biomarkers, including clinical, oxidative stress and metabolic markers, peptide mediators and red blood cell membrane lipids. By using a synthetic data-driven modeling based on principal component and correlation analyses, we provided evidence that, besides the early, well-known glucose metabolism- and weight loss-associated beneficial effects of BS, a tardive, weight-independent increase of the hepatic cholesterol metabolism occurs that is associated with potentially detrimental inflammatory and metabolic effects. Canonical correlation analysis indicated that oxidative stress is the most predictive feature of the BS-induced changes of both glucose and lipids metabolism. Our results show the power of multi-level correlation analysis to uncover the network of biological pathways affected by BS. This approach highlighted potential health risks of restrictive BS that are disregarded with the current practice to use weight loss as surrogate of BS success.

Ketogenic Diet for Preoperative Weight Reduction in Bariatric Surgery: A Narrative Review.

Bariatric surgery (BS) is the most effective treatment in reducing weight and the burden of comorbidities in patients with severe obesity. Despite the overall low mortality rate, intra- and post-operative complications remains quite common. Weight loss before BS reduces surgical risk, but studies are inconclusive regarding which is the best approach to apply. In this review, we summarize the current evidence on the effect of a ketogenic diet (KD) before BS. All studies agree that KD leads to considerable weight loss and important improvements in terms of surgical risk, but populations, interventions and outcomes are very heterogeneous. KD appears to be a safe and effective approach to induce weight loss before BS. However, randomized controlled trials with better-defined dietary protocols and homogeneous outcomes are necessary in order to draw firm conclusions.

Bariatric surgery for metabolic unhealthy obesity (MUO) during the COVID era: short-term results of a high-volume center.

PURPOSE: During the coronavirus disease 19 (COVID-19) outbreak, most public hospitals worldwide have been forced to postpone a major part of bariatric surgery (BS) operations with unfavorable consequences for weight and obesity complications. The aim of this study was to evaluate the effectiveness and safety of laparoscopic BS on subjects with metabolically unhealthy obesity (MUO) during COVID-19 pandemic in a high-volume Italian center. METHODS: Between March 2020 and January 2021, all patients with MUO submitted to laparoscopic BS (sleeve gastrectomy [SG], one anastomosis gastric bypass [OAGB] and Roux-en-Y gastric bypass [RYGB]) were enrolled according to the ATP III Guidelines, with a minimum follow-up of 3 months. RESULTS: In the study period, 210 patients with MUO underwent laparoscopic BS (77 RYGB, 85 SG and 48 OAGB) in our obesity referral center. Postoperative major complications occurred in 4 patients (1.9%) with zero mortality. At 9-month follow-up, a total weight loss (TWL) of 28.2 ± 18.4, 26.1 ± 23.1 and 24.5 ± 11.3% (p = 0.042) was observed in RYGB, OAGB and SG groups, respectively. The rate of comorbidity resolution was very similar for all type of surgeries (p = 0.871). Only two cases of postoperative SARS-CoV-2 infection were registered (0.9%) and both cases resolved with medical therapy and observation. CONCLUSION: Among the patients studied, all surgical techniques were safe and effective for MUO during the COVID era. This group of patients is at high risk for general and SARS-CoV-2-related mortality and therefore should be prioritized for BS. LEVEL OF EVIDENCE: Level III, single-center retrospective cohort study.

Updating obesity management strategies: an audit of Italian specialists.

Obesity negatively affects physical and psychological health and increases health care costs. Although there is increasing interest in early diagnosis and timely intervention, there are several principles of care included in the current guidelines for clinical management of obesity that can potentially be updated and improved to address the "clinical inertia" and, consequently, to optimize the management of adult obesity. Using an online Delphi-based process, an Italian board of experts involved in the management of obesity discussed the usefulness of a pro-active approach to the care of patients with obesity, providing a consensus document with practical indications to identify risk factors for morbidity and death and raise awareness throughout the treatment continuum, including the early stages of the disease. In clinical practice, it seems inappropriate to delay an intervention that could avoid progression to a more severe level of obesity and/or prevent the onset of obesity-related comorbidities.Level of evidence Level V, report of expert committee.

Inflammation, underweight, malignancy and a marked catabolic state as predictors for worse outcomes in COVID-19 patients with moderate-to-severe disease admitted to Internal Medicine Unit.

INTRODUCTION: During COVID-19 pandemic, Internal Medicine Units (IMUs) accounted for about 70% of patients hospitalized. Although a large body of data has been published regarding the so-called first wave of the pandemic, little is known about the characteristics and predictors of worse outcomes of patients managed in IMUs during the second wave. METHODS: We prospectively assessed demographics, comorbidities, treatment and outcomes, including ventilation support (VS) and death, in patients admitted to our IMU for SARS-CoV-2 between October 13th, 2020 and January 21st, 2021. Clinical evolution and biochemical testing 1, 7 and 14 days after COVID-19 diagnosis were recorded. RESULTS: We studied 120 patients (M/F 56/64, age 71±14.5 years) admitted to our IMU. Most of them had at least one comorbidity (80%). Patients who died were older, more frequently underweight, affected by malignant neoplasms and on statin therapy compared to patients eventually discharged. Both worse outcome groups (VS and death) presented higher neutrophils, ferritin, IL-6 and lower total proteins levels than controls. Age was significantly associated with mortality but not with VS need. The multivariate analysis showed age and gender independent association of mortality with underweight, malignancy and antibiotics use at the admission. With regard to biochemical parameters, both unfavourable outcomes were positively associated with high WBC count, neutrophils, blood urea nitrogen and low serum total proteins. CONCLUSIONS: Our study identified inflammation, underweight, malignancy and a marked catabolic state as the main predictors for worse outcomes in COVID-19 patients admitted to IMU during the so-called second wave of the pandemic.

Obesity management: at the forefront against disease stigma and therapeutic inertia.

Obesity is a complex chronic relapsing disease, resulting from the interaction between multiple environmental, genetic and epigenetic causes, and supported by changes in the neuroendocrine mechanisms regulating energy balance and body weight. Adipose tissue dysfunction contributes to obesity-related complications. However, the prevalent narrative about the causes and mechanisms of obesity remains a much more simplistic one, based on the false assumption that individuals can fully control their body weight through appropriate behavioural choices. According to this narrative, obesity is simply reversible "persuading" the patient to follow healthier and more virtuous individual behaviours (moral judgement). This persistent narrative forms the deep root of the stigmatisation of people with obesity at the individual level and creates a clear discrepancy on how obesity prevention and cure are designed in comparison with the case of other non-communicable chronic diseases (clinical stigma). The promotion of systemic preventive measures against obesity is not supported at a political and social level by the persistence of a narrative of obesity as the simple consequence of individual failures and lack of willpower. The simplistic narrative of obesity as a self-imposed condition with an easy way-out ("eat less and move more") creates a clear discrepancy on how obesity is managed by health care systems in comparison with other NCDs. The over-estimation of the efficacy of therapeutic intervention solely based on patients education and lifestyle modification is responsible of therapeutic inertia in health care professionals and in clinical guidelines, limiting or delaying the adoption of more effective therapeutic strategies, like anti-obesity medications and bariatric surgery. In conclusion, the persistence of a narrative describing obesity as a self-induced easily reversible condition has profound consequences on how obesity prevention and management are build, including the design and implementation of obesity management guidelines and a tendency to therapeutic inertia.Level of evidence: No level of evidence.

Long-Term Iron and Vitamin B12 Deficiency Are Present after Bariatric Surgery, Despite the Widespread Use of Supplements.

There are few long-term nutritional studies in subjects undergoing bariatric surgery that have assessed weight regain and nutritional deficiencies. In this study, we report data 8 years after surgery on weight loss, use of dietary supplements and deficit of micronutrients in a cohort of patients from five centres in central and northern Italy. The study group consisted of 52 subjects (age: 38.1 ± 10.6 y, 42 females): 16 patients had Roux-en-Y gastric bypass (RYGB), 25 patients had sleeve gastrectomy (SG) and 11 subjects had adjustable gastric banding (AGB). All three bariatric procedures led to sustained weight loss: the average percentage excess weight loss, defined as weight loss divided by excess weight based on ideal body weight, was 60.6% ± 32.3. Despite good adherence to prescribed supplements, 80.7% of subjects (72.7%, AGB; 76.7%, SG; 93.8 %, RYGB) reported at least one nutritional deficiency: iron (F 64.3% vs. M 30%), vitamin B12 (F 16.6% vs. M 10%), calcium (F 33.3% vs. M 0%) and vitamin D (F 38.1% vs. M 60%). Long-term nutritional deficiencies were greater than the general population among men for iron and among women for vitamin B12.

Is type 2 diabetes an adiposity-based metabolic disease? From the origin of insulin resistance to the concept of dysfunctional adipose tissue.

In the last decades of the past century, a remarkable amount of research efforts, money and hopes was generated to unveil the basis of insulin resistance that was believed to be the primary etiological factor in the development of type 2 diabetes. From the Reaven's insulin resistance syndrome to the DeFronzo's triumvirate (skeletal muscle, liver and beta-cell) and to Kahn's discovery (among many others) of insulin receptor downregulation and autophosphorylation, an enthusiastic age of metabolic in vivo and in vitro research took place, making the promise of a resolutory ending. However, from many published data (those of insulin receptoropathies and lipodystrophies, the genome-wide association studies results, the data on reversibility of type 2 diabetes after bariatric surgery or very-low-calorie diets, and many others) it appears that insulin resistance is not a primary defect but it develops secondarily to increased fat mass. In particular, it develops from a mismatch between the surplus caloric intake and the storage capacity of adipose tissue. On this basis, we propose to change the today's definition of type 2 diabetes in adiposity-based diabetes.Level of Evidence as a narrative review a vast array of studies have been included in the analysis, ranging from properly designed randomized controlled trials to case studies; however, the overall conclusion may be regarded as level IV.

The European Association for the Study of Obesity (EASO) Endorses the Milan Charter on Urban Obesity.

The Milan Charter on Urban Obesity highlights the challenges of urban environments as a battleground for human health, as cities are often organized to subvert public health goals, and promote rather than prevent the development of obesity and consequent non-communicable diseases. The Charter articulates ten principles which detail actions and strategies through which general practitioners, diverse medical specialists, related healthcare professionals, administrators and healthcare practice managers, policy actors - within health systems and at a national level - along with experts across disciplines, and citizens, can work in cooperation to meet this challenge and improve public health. The Charter urges the adoption of decisions that deliver the following: (i) policies which enable our cities to become healthier and less obesogenic, more supportive of well-being and less health-disruptive in general, and (ii) policies that fully support primary prevention strategies, that address social stigma, and that ensure fair access to treatment for people living with obesity. The Milan Charter on Urban Obesity aims to raise awareness of our shared responsibility for the health of all citizens, and focuses on addressing the health of people living with obesity - not only as a challenge in its own right, but a gateway to other major non-communicable diseases, including cardiovascular diseases, type 2 diabetes, and some cancers.

Tyrosol May Prevent Obesity by Inhibiting Adipogenesis in 3T3-L1 Preadipocytes.

Tyrosol (TR), a major polyphenol found in extra virgin olive oil (EVOO), exerts several antioxidant effects. However, only scarce evidences are present regarding its activity on adipocytes and obesity. This study evaluated the role of TR in adipogenesis. Murine 3T3-L1 preadipocytes were incubated with TR (300 and 500 µM), and TR administration inhibited adipogenesis by downregulation of several adipogenic factors (leptin and aP2) and transcription factors (C/EBPα, PPARγ, SREBP1c, and Glut4) and by modulation of the histone deacetylase sirtuin 1. After complete differentiation, adipocytes treated with 300 and 500 µM TR showed a reduction of 20% and 30% in lipid droplets, respectively. Intracellular triglycerides were significantly reduced after TR treatment (p < 0.05). Mature adipocytes treated with TR at 300 and 500 µM showed a marked decrease in the inflammatory state and oxidative stress as shown by the modulation of specific biomarkers (TNF, IL6, ROS, and SOD2). TR treatment also acted on the early stage of differentiation by reducing cell proliferation (~40%) and inducing cell cycle arrest during Mitotic Expansion Clonal (first 48 h of differentiation), as shown by the increase in both S1 phase and p21 protein expression. We also showed that TR induced lipolysis by activating the AMPK-ATGL-HSL pathway. In conclusion, we provided evidence that TR reduces 3T3-L1 differentiation through downregulation of adipogenic proteins, inflammation, and oxidative stress. Moreover, TR may trigger adipose tissue browning throughout the induction of the AMPK-ATGL-UCP1 pathway and, subsequently, may have promise as a potential therapeutic agent for the treatment and prevention of obesity.

Peroxiredoxin6, a Multitask Antioxidant Enzyme Involved in the Pathophysiology of Chronic Noncommunicable Diseases.

SIGNIFICANCE: Chronic noncommunicable diseases (NCDs) are the leading causes of disability and death worldwide. NCDs mainly comprise diabetes mellitus, cardiovascular diseases, chronic obstructive pulmonary disease, cancer, and neurological degenerative diseases, which kill more than 80% of population, especially the elderly, worldwide. Recent Advances: Several recent theories established NCDs as multifactorial diseases, where a combination of genetic, epigenetic, and environmental factors contributes to their pathogenesis. Nevertheless, recent findings suggest that the common factor linking all these pathologies is an increase in oxidative stress and the age-related loss of the antioxidant mechanisms of defense against it. Impairment in mitochondrial homeostasis with consequent deregulation in oxidative stress balance has also been suggested. CRITICAL ISSUES: Therefore, antioxidant proteins deserve particular attention for their potential role against NCDs. In particular, peroxiredoxin(Prdx)6 is a unique antioxidant enzyme, belonging to the Prdx family, with double properties, peroxidase and phospholipase activities. Through these activities, Prdx6 has been shown to be a powerful antioxidant enzyme, implicated in the pathogenesis of different NCDs. Recently, we described a phenotype of diabetes mellitus in Prdx6 knockout mice, suggesting a pivotal role of Prdx6 in the pathogenesis of cardiometabolic diseases. FUTURE DIRECTIONS: Increasing awareness on the role of antioxidant defenses in the pathogenesis of NCDs may open novel therapeutic approaches to reduce the burden of this pandemic phenomenon. However, knowledge of the role of Prdx6 in NCD prevention and pathogenesis is still not clarified.

Peroxiredoxin 6 Is a Key Antioxidant Enzyme in Modulating the Link between Glycemic and Lipogenic Metabolism.

Insulin action and often glucose-stimulated insulin secretion are reduced in obesity. In addition, the excessive intake of lipids increases oxidative stress leading to overt type 2 diabetes mellitus (T2DM). Among the antioxidative defense systems, peroxiredoxin 6 (PRDX6) is able to reduce H2O2 and short chain and phospholipid hydroperoxides. Increasing evidences suggest that PRDX6 is involved in the pathogenesis of atherosclerosis and T2DM, but its role in the etiopathology of obesity and its complications is still not known. Therefore, in the present study, we sought to investigate this association by using PRDX6 knockout mice (PRDX6-/-). Metabolic parameters, like carbon dioxide (VCO2) production, oxygen consumption (VO2), and the respiratory exchange ratio (RER), were determined using metabolic cages. Intraperitoneal insulin and glucose tolerance tests were performed to evaluate insulin sensitivity and glucose tolerance, respectively. Liver and pancreas histochemical analyses were also evaluated. The expression of enzymes involved in lipid and glucose metabolism was analyzed by real-time PCR. Following 24 weeks of high-fat-diet (HFD), PRDX6-/- mice showed weight gain and higher food and drink intake compared to controls. VO2 consumption and VCO2 production decreased in PRDX6-/- mice, while the RER was lower than 0.7 indicating a prevalent lipid metabolism. PRDX6-/- mice fed with HFD showed a further deterioration on insulin sensitivity and glucose-stimulated insulin secretion. Furthermore, in PRDX6-/- mice, insulin did not suppress adipose tissue lipolysis with consequent hepatic lipid overload and higher serum levels of ALT, cholesterol, and triglycerides. Interestingly, in PRDX6-/- mice, liver and adipose tissue were associated with proinflammatory gene upregulation. Finally, PRDX6-/- mice showed a higher rate of nonalcoholic steatohepatitis (NASH) compared to control. Our results suggest that PRDX6 may have a functional and protective role in the development of obesity-related metabolic disorders such as liver diseases and T2DM and may be considered a potential therapeutic target against these illnesses.

Obesity phenotypes: depot-differences in adipose tissue and their clinical implications.

Obesity, defined as excess fat mass, increases risks for multiple chronic diseases, such as type 2 diabetes, cardiovascular disease, and several types of cancer. Beyond adiposity per se, the pattern of fat distribution, android or truncal as compared to gynoid or peripheral, has a profound influence on systemic metabolism and hence risk for obesity complications. Not only factors as genetics, environment, gender, and age account for the apparent compartmentalization of white adipose tissue (WAT) in the body. Indeed, the heterogeneity among different anatomical depots also appears to stem from their intrinsic diversity, including cellular developmental origin, proliferative capacity, glucose and lipid metabolism, insulin sensitivity, cytokine pattern, thermogenic ability, and vascularization. Under the obese condition, these depot-specific differences translate into specific WAT distribution patterns, giving rise to different cardiometabolic consequences. This review summarizes the clinical and mechanistic evidence for the depot-specific differences and the phenotypic characteristics of different WAT depots that link their depot-specific biology to obesity-specific complications.

Parathyroid hormone in surgery-induced weight loss: no glucometabolic effects but potential adaptive response to skeletal loading.

PURPOSE: Increased parathyroid hormone (PTH) is commonly associated with obesity, and its role in the pathogenesis of obesity-related glucometabolic abnormalities is uncertain. We aimed to explore the relationships of PTH with glucose/insulin homeostasis parameters before and after bariatric surgery-induced weight loss, and whether they depend or not on 25-hydroxyvitamin D (25OHD) status. METHODS: We included 42 subjects (27 women, aged 40 ± 5 years, BMI 48.5 ± 7.3 kg/m2) without diabetes, chronic kidney disease, or hyperparathyroidism undergoing sleeve gastrectomy. The following parameters were evaluated before and 6 months after surgery: circulating levels of PTH, calcium, phosphorus, 25OHD, leptin, insulin growth factor (IGF)-1; 75-g oral glucose tolerance test to derive measures of insulin sensitivity (ISI) and secretion (Stumvoll index); dual-energy X-ray absorptiometry to assess fat distribution and bone mineral density. RESULTS: Weight loss was accompanied by significant reduction of PTH levels (77.9 ± 19.1 vs. 60.5 ± 13.4 pg/ml; p = 0.005), without concomitant modification of 25OHD status. Both baseline PTH and its postoperative percent change resulted associated, with baseline fat mass (ß = 0.615, p = 0.003) and its concurrent postoperative reduction (r = 0.419; p = 0.006), but neither with glucose homeostasis parameters nor their respective variations after weight loss. Interestingly, leptin reduction after weight loss was independently related to PTH change (ß = 0.396, p = 0.015) and IGF-1 levels (ß = 0.176, p = 0.059). CONCLUSIONS: Circulating PTH decreases with fat mass reduction independent of 25OHD status, but it  is not associated with improvement of insulin resistance and related metabolic parameters. Leptin and PTH may mediate the cross-talk between adipose tissue and parathyroid glands, which possibly contributes to bone adaptation to excess body weight.

Epicardial adipose tissue: at the heart of the obesity complications.

In recent years, the anatomic and functional contiguity of epicardial adipose tissue (EAT) to myocardium and coronary arteries has gained increasing interest for its potential pathogenetic role in obesity-related cardiac diseases. Besides its known and attributed biochemical cardioprotective properties, it is becoming evident that, in metabolic disease states, EAT-secreted bioactive molecules may play an important role in the pathogenesis of coronary artery disease and cardiac arrhythmias. EAT-derived inflammatory cytokines and reactive oxidative species may, indeed, play a part in the development of a local proatherogenic milieu by paracrine and vasocrine mechanisms of interaction. In addition, initial clinical and in vitro studies have pointed out that EAT could be a determinant of the substrate of atrial fibrillation by contributing to the structural and electrical remodeling of myocardium. This article reviews the current state of knowledge on the association of EAT with cardiac dysfunction and the potential factors mediating the cross talk between this fat depot and the underlying cardiac structures.