The incidence of cardiac arrhythmias during exercise stress testing: a focus on patients with severe obesity undergoing sleeve gastrectomy.

INTRODUCTION: Obesity is associated with a higher risk of cardiac arrhythmias. Sleeve gastrectomy (SG) is a common bariatric surgery with beneficial effects on weight loss and comorbidities. The study aimed to investigate the prevalence of arrhythmias during maximal exercise testing in patients with moderate-severe obesity and to evaluate the impact of SG on these arrhythmic events. METHODS: All patients with moderate or severe obesity who were considered suitable candidates for SG between June 2015 and September 2020 were recruited. Each patient underwent three incremental, maximal, ECG-monitored cardiopulmonary exercise test 1 month before and 6 and 12 months after SG; the frequency and complexity of ventricular premature beats (VPBs) and atrial premature beats (APBs) have been evaluated during rest, exercise and recovery phases. RESULTS: Fifty patients with severe obesity (BMI 46.39 ± 7.89 kg/m2) were included in the study. After SG, patients presented a decreased BMI (34.15 ± 6.25 kg/m2 at 6 months post-SG and 31.87 ± 5.99 kg/m2 at 12 months post-SG). At 6 months post-SG, an increase in VPBs, mainly during the recovery phase, was observed. At 12 months post-SG, a reduction in VPBs compared with the 6 months evaluation was showed. CONCLUSION: Although in the early post-surgical phase the risk of exercise-induced arrhythmias may be higher, SG does not seem to increase the occurrence of arrhythmias in the long-term. No life-threating arrhythmias were found during post-SG evaluations.

Low-grade inflammation, CoVID-19, and obesity: clinical aspect and molecular insights in childhood and adulthood.

The new 2019 coronavirus 19 disease (CoVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to health systems. As a global health problem, this pandemic poses a huge threat to people and is responsible for significant morbidity and mortality worldwide. On the other hand, obesity has also reached epidemic proportions and poses another challenge to the healthcare system. There is increasing evidence of a strong association between obesity and CoVID-19 disease, but the mechanisms underlying the link between the two remain unclear and the role of obesity also remains to be elucidated. In particular obesity-related low-grade inflammation has been hypothesized as the Achille's heel that could predispose subjects with obesity to a more severe CoVID-19 compared to subjects with normal weight. Hence, we summarized recent evidence on the role of low-grade inflammation in clinical aspects of CoVID-19 in subjects with obesity in both childhood and adulthood. Further, we provide molecular insights to explain this link.

Adipogenic progenitors in different organs: Pathophysiological implications.

In physiological conditions, the adipose organ resides in well-defined areas, where it acts providing an energy supply and as an endocrine organ involved in the control of whole-body energy metabolism. Adipose tissue adipokines connect the body's nutritional status to the regulation of energy balance. When it surrounds organs, it provides also for mechanical protection. Adipose tissue has a complex and heterogenous cellular composition that includes adipocytes, adipose tissue-derived stromal and stem cells (ASCs) which are mesenchymal stromal cells, and endothelial and immune cells, which signal to each other and to other tissues to maintain homeostasis. In obesity and in other nutrition related diseases, as well as in age-related diseases, biological and functional changes of adipose tissue give rise to several complications. Obesity triggers alterations of ASCs, impairing adipose tissue remodeling and adipose tissue function, which induces low-grade systemic inflammation, progressive insulin resistance and other metabolic disorders. Adipose tissue grows by hyperplasia recruiting new ASCs and by hypertrophy, up to its expandability limit. To overcome this limitation and to store the excess of nutrients, adipose tissue develops ectopically, involving organs such as muscle, bone marrow and the heart. The origin of ectopic adipose organ is not clearly elucidated, and a possible explanation lies in the stimulation of the adipogenic differentiation of mesenchymal precursor cells which normally differentiate toward a lineage specific for the organ in which they reside. The chronic exposition of these newly-formed adipose depots to the pathological environment, will confer to them all the phenotypic characteristics of a dysfunctional adipose tissue, perpetuating the organ alterations. Visceral fat, but also ectopic fat, either in the liver, muscle or heart, can increase the risk of developing insulin resistance, type 2 diabetes, and cardiovascular diseases. Being able to prevent and to target dysfunctional adipose tissue will avoid the progression towards the complications of obesity and other nutrition-related diseases. The aim of this review is to summarize some of the knowledge regarding the presence of adipose tissue in particular tissues (where it is not usually present), describing the composition of its adipogenic precursors, and the interactions responsible for the development of organ pathologies.

Cardiopulmonary exercise testing in patients with moderate-severe obesity: a clinical evaluation tool for OSA?

PURPOSE: Obstructive sleep apnea (OSA) is a widespread comorbidity of obesity. Nasal continuous positive airway pressure (CPAP) has been demonstrated very effective in treating patients with OSA. The aims of this study were to investigate whether or not cardiopulmonary exercise testing (CPET) can characterize patients with OSA and to evaluate the effect of nasal CPAP therapy. METHODS: An observational study was conducted on patients with moderate to severe obesity and suspected OSA. All patients underwent cardiorespiratory sleep study, spirometry, and functional evaluation with ECG-monitored, incremental, maximal CPET. RESULTS: Of the 147 patients, 94 presented with an apnea-hypopnea index (AHI) ≥ 15 events/h and were thus considered to have OSA (52 receiving nasal CPAP treatment; 42 untreated) while 53 formed a control group (AHI < 15 events/h). Patients with untreated OSA showed significantly lower oxygen uptake (VO2), heart rate, minute ventilation (VE), and end tidal carbon dioxide (PETCO2) at peak exercise compared to controls. Patients receiving nasal CPAP showed higher VE and VO2 at peak exercise compared to untreated patients. A difference in PETCO2 between the maximum value reached during test and peak exercise (ΔPETCO2 max-peak) of 1.71 mmHg was identified as a predictor of OSA. CONCLUSION: Patients with moderate to severe obesity and untreated OSA presented a distinctive CPET-pattern characterized by lower aerobic and exercise capacity, higher PETCO2 at peak exercise associated with a lower ventilatory response. Nasal CPAP treatment was shown to positively affect these cardiorespiratory adaptations during exercise. ΔPETCO2 max-peak may be used to suggest OSA in patients with obesity.

Association of obstructive sleep apnea with non-alcoholic fatty liver disease in patients with obesity: an observational study.

PURPOSE: Obstructive Sleep Apnea (OSA) is associated with the presence and severity of Non-Alcoholic Fatty Liver Disease (NAFLD). We aimed to investigate the relationship between the severity of OSA and NAFLD and to recognize a polysomnographic parameter correlated with progression of fibrosis, determined by a non-invasive score of liver fibrosis, FIBrosis-4 index (FIB-4), in patients affected by severe obesity and OSA. METHODS: We enrolled 334 patients (Body Mass Index, BMI 44.78 ± 8.99 kg/m2), divided into classes according to severity of OSA evaluated with Apnea Hypopnea Index (AHI): OSAS 0 or absent (17%), mild OSA (26%), moderate OSA (20%), severe OSAS (37%). We studied anthropometric, polysomnographic, biochemical data and FIB-4. A multiple regression model was computed to identify a polysomnographic independent predictor of FIB-4 among those parameters previously simple correlated with FIB-4. RESULTS: The severity of OSA was associated with a decrease in High-Density Lipoprotein-cholesterol (HDL) and an increase in BMI, triglycerides, Homeostasis model assessment insulin-resistance index (HOMA), transaminases and FIB-4. FIB-4 correlated with sex, age, BMI, AHI, mean percentage oxyhaemoglobin (meanSaO2%), number of desaturations, platelets, transaminases, HDL, triglycerides and HOMA. The only variables independently related to FIB-4 were sex, BMI, triglycerides and meanSpO2 (r = 0.47, AdjRsqr = 0.197). CONCLUSION: MeanSpO2% represented an independent determinant for the worsening of FIB-4 in patients with severe obesity and OSA. Hence, it could hypothesize a clinical role of meanSaO2% in recognizing patients with obesity and OSA and higher risk of developing advanced fibrosis and, thus, to undergo further investigation. LEVEL III: Evidence obtained from well-designed cohort analytic studies.

In vitro chronic glycation induces AGEs accumulation reducing insulin-stimulated glucose uptake and increasing GLP1R in adipocytes.

Intracellular AGEs accumulation increases RAGE and GLP1R and reduces glucose uptake in adipocytes.

Spot-light on microbiota in obesity and cancer.

Over the last few years, the complexity and diversity of gut microbiota within and across individuals has been detailed in relation to human health. Further, understanding of the bidirectional association between gut microbiota and metabolic disorders has highlighted a complimentary, yet crucial role for microbiota in the onset and progression of obesity-related cancers. While strategies for cancer prevention and cure are known to work efficiently when supported by healthy diet and lifestyle choices and physical activity, emerging evidence suggests that the complex interplay relating microbiota both to neoplastic and metabolic diseases could aid strategies for cancer treatment and outcomes. This review will explore the experimental and clinical grounds supporting the functional role of gut microbiota in the pathophysiology and progression of cancers in relation to obesity and its metabolic correlates. Therapeutic approaches aiding microbiota restoration in connection with cancer treatments will be discussed.

Edmonton Obesity Staging System: an improvement by cardiopulmonary exercise testing.

BACKGROUND/OBJECTIVES: Different approaches are used to classify obesity severity. Beyond classical anthropometric measurements, the Edmonton Obesity Staging System (EOSS) considers medical, physical and psychological parameters. However, this method has some limitations, principally due to the absence of an objective measure for physical impairment. The aim of our study is thus to overcome this limitation suggesting a new functional parameter obtained by cardiopulmonary exercise testing (CPET), i.e., cardiorespiratory fitness (CRF), expressed as weight-adjusted peak oxygen consumption (VO2peak/kg). SUBJECTS/METHODS: This observational cross-sectional study conducted on a population of 843 patients affected by obesity finally enrolled 500 subjects. Every patient underwent clinical, anthropometric, biochemical assessment and CPET. First, participants have been classified according to standard EOSS in five stages. Second, patients were reclassified according to the new modified EOSS (EOSS-CRF) based on their age- and gender-appropriate VO2peak/kg percentiles as reported in the healthy normal-weight population of the FRIEND registry. RESULTS: VO2peak/kg was significantly different between standard EOSS classes 1 and 2 and classes 1 and 3 (ANCOVA p model = 0.004), whereas patients in classes 2 and 3 showed similar CRF. The EOSS-CRF classification varied in number of patients in each class compared to EOSS, particularly with a shift from class 2 to class 3. Moreover, CRF showed that physical impairment is less addressed by EOSS when compared to EOSS-CRF. CONCLUSIONS: The integration of EOSS with CRF allowed us to assign to each patient a severity index that considers not only clinical parameters, but also their functional impairment through a quantitative and prognostically important parameter (VO2peak/kg). This improvement of the staging system may also provide a better approach to identify individuals at increased risk of mortality leading to targeted therapeutic management and prognostic risk stratification for patients with obesity.

Correction to: Diet approach before and after bariatric surgery.

The original version of this article unfortunately, has the incorrect title reported in the published paper.

Diet approach before and after bariatric surgery.

Bariatric surgery (BS) is today the most effective therapy for inducing long-term weight loss and for reducing comorbidity burden and mortality in patients with severe obesity. On the other hand, BS may be associated to new clinical problems, complications and side effects, in particular in the nutritional domain. Therefore, the nutritional management of the bariatric patients requires specific nutritional skills. In this paper, a brief overview of the nutritional management of the bariatric patients will be provided from pre-operative to post-operative phase. Patients with severe obesity often display micronutrient deficiencies when compared to normal weight controls. Therefore, nutritional status should be checked in every patient and correction of deficiencies attempted before surgery. At present, evidences from randomized and retrospective studies do not support the hypothesis that pre-operative weight loss could improve weight loss after BS surgery, and the insurance-mandated policy of a preoperative weight loss as a pre-requisite for admission to surgery is not supported by medical evidence. On the contrary, some studies suggest that a modest weight loss of 5-10% in the immediate preoperative period could facilitate surgery and reduce the risk of complications. Very low calories diet (VLCD) and very low calories ketogenic diets (VLCKD) are the most frequently used methods for the induction of a pre-operative weight loss today. After surgery, nutritional counselling is recommended in order to facilitate the adaptation of the eating habits to the new gastro-intestinal physiology. Nutritional deficits may arise according to the type of bariatric procedure and they should be prevented, diagnosed and eventually treated. Finally, specific nutritional problems, like dumping syndrome and reactive hypoglycaemia, can occur and should be managed largely by nutritional manipulation. In conclusion, the nutritional management of the bariatric patients requires specific nutritional skills and the intervention of experienced nutritionists and dieticians.

White Adipose Tissue Expansion in Multiple Symmetric Lipomatosis Is Associated with Upregulation of CK2, AKT and ERK1/2.

Multiple symmetric lipomatosis (MSL) is a rare disorder characterized by overgrowing lipomatous tissue (LT) in the subcutaneous adipose tissue (SAT). What LT is and how it expands are not completely understood; previous data suggested that it could derive from brown AT precursors. In six MSL type I patients, we compared LT morphology by histological and immunohistochemistry (IHC) analysis, gene expression, by qPCR, kinase activity, by Western Blot and in vitro assay to paired-control SAT using AT from patients with pheochromocytoma as a human browning reference. In the stromal vascular fraction (SVF), we quantified adipose stem cells (ASCs) by flow cytometry, the proliferation rate, white and beige adipogenic potential and clonogenicity and adipogenicity by a limiting dilution assay. LT displayed white AT morphology and expression pattern and did not show increased levels of the brown-specific marker UCP1. In LT, we evidenced AKT, CK2 and ERK1/2 hyperactivation. LT-SVF contained increased ASCs, proliferated faster, sprouted clones and differentiated into adipocytes better than the control, displaying enhanced white adipogenic potential but not increased browning compared to SAT. In conclusion, LT is a white AT depot expanding by hyperplasia through increased stemness and enhanced white adipogenesis upregulating AKT, CK2 and ERK1/2, which could represent new targets to counteract MSL.

Comparison of Cardiorespiratory Fitness Prediction Equations and Generation of New Predictive Model for Patients with Obesity.

PURPOSE: Cardiorespiratory fitness (CRF) is a critical marker of overall health and a key predictor of morbidity and mortality, but the existing prediction equations for CRF are primarily derived from general populations and may not be suitable for patients with obesity. METHODS: Predicted CRF from different non-exercise prediction equations was compared with measured CRF of patients with obesity who underwent maximal cardiopulmonary exercise testing (CPET). Multiple linear regression was used to develop a population-specific non-exercise CRF prediction model for treadmill exercise including age, sex, weight, height and physical activity level as determinants. RESULTS: 660 patients underwent CPET during the study period. Within the entire cohort, R2 values had a range of 0.24-0.46. Predicted CRF was statistically different from measured CRF for 19 included equations. Only 50% of patients were correctly classified into the measured CRF categories according to predicted CRF. A multiple model for CRF prediction (ml/min) was generated (R2 = 0.78) and validated using two cross-validation methods. CONCLUSIONS: Most used equations provide inaccurate estimates of CRF in patients with obesity, particularly in cases of severe obesity and low CRF. Therefore, a new prediction equation was developed and validated specifically for patients with obesity, offering a more precise tool for clinical CPET interpretation and risk stratification in this population.

SGLT2 Inhibitors in the Management of Type 1 Diabetes (T1D): An Update on Current Evidence and Recommendations.

SGLT2i (sodium glucose transporter type 2 inhibitors) are pharmacological agents that act by inhibiting the SGLT2, by reducing the renal plasma glucose threshold and inducing glycosuria, resulting in a blood glucose lowering effect. In recent years, studies demonstrating some additional positive effects of SGLT2i also in the treatment of T1D have increased progressively. The SGLT2i dapagliflozin and sotagliflozin have been temporarily licensed for use by the European Medical Agency (EMA) as an adjunct to insulin therapy in adults with T1D with a body mass index of 27 kg/m2 or higher. However, in the meantime, the US Food and Drug Administration (FDA) Endocrinologic and Metabolic Drugs Advisory Committee was divided, citing concerns about the main side effects of SGLT2i, especially diabetic ketoacidosis (DKA). The aim of this manuscript was to conduct an update on current evidence and recommendations of the reported use of SGLT2i in the treatment of T1D in humans. Preclinical studies, clinical trial and real world data suggest benefits in glycaemia control and nefro-cardiovascular protection, even though several studies have documented an important increase in the risk of DKA, a serious and life-threatening adverse event of these agents. SGLT2i potentially addresses some of the unmet needs associated with T1D by improving glycaemic control with weight loss and without increasing hypoglycemia, by reducing glycaemic variability. However, due to side effects, EMA recommendation for SGLT2 use on T1D was withdrawn. Further studies will be needed to determine the safety of this therapy in T1D and to define the type of patient who can benefit most from these medications.

Obesity, the Adipose Organ and Cancer in Humans: Association or Causation?

Epidemiological observations, experimental studies and clinical data show that obesity is associated with a higher risk of developing different types of cancer; however, proof of a cause-effect relationship that meets the causality criteria is still lacking. Several data suggest that the adipose organ could be the protagonist in this crosstalk. In particular, the adipose tissue (AT) alterations occurring in obesity parallel some tumour behaviours, such as their theoretically unlimited expandability, infiltration capacity, angiogenesis regulation, local and systemic inflammation and changes to the immunometabolism and secretome. Moreover, AT and cancer share similar morpho-functional units which regulate tissue expansion: the adiponiche and tumour-niche, respectively. Through direct and indirect interactions involving different cellular types and molecular mechanisms, the obesity-altered adiponiche contributes to cancer development, progression, metastasis and chemoresistance. Moreover, modifications to the gut microbiome and circadian rhythm disruption also play important roles. Clinical studies clearly demonstrate that weight loss is associated with a decreased risk of developing obesity-related cancers, matching the reverse-causality criteria and providing a causality correlation between the two variables. Here, we provide an overview of the methodological, epidemiological and pathophysiological aspects, with a special focus on clinical implications for cancer risk and prognosis and potential therapeutic interventions.

Oxidized cellulose nanofibers from sugarcane bagasse obtained by microfluidization: Morphology and rheological behavior.

It is advantageous to understand the relationship between cellulose fiber morphology and the rheological behavior of its dispersions so that their application can be optimized. The goal of this study was to produce sugarcane bagasse-sourced cellulose dispersions with different numbers of high-pressure homogenization cycles. Microfluidization produced cellulose nanofibers (between 5 and 80 nm in diameter) with similar surface charge densities and crystallinities (measured on the resulting films). Oscillatory rheology showed that TEMPO-oxidized cellulose dispersions exhibited gel-like behavior. However, not only did the samples with more microfluidization cycles present a lower storage modulus, but the sample with 100 cycles completely lost the gel-like characteristic, presenting a viscous fluid rheological behavior. Thixotropy loop tests revealed the influence of nanofiber length on the dispersion's structure, as evidenced by the decrease in the hysteresis value along with fiber breakage. Therefore, our findings demonstrate that the rheological properties of the dispersion can be tuned according to the length of the nanofibers, allowing for targeted applications.

Real-time monitoring of the starch cross-linking with citric acid by chemorheological analysis.

Cross-linking has been used as a strategy to improve the mechanical properties of starch films. However, the concentration of the cross-linking agent and the cure time and temperature determine the structure and properties of the modified starch. This article, for the first time, reports the chemorheological study of cross-linked starch films with citric acid (CA) through monitoring the storage modulus as a function of time G'(t). In this study, a CA concentration of 10 phr showed a pronounced increase of G'(t) during the cross-linking of starch, followed by a constant plateau. Analyses of infrared spectroscopy validated the result chemorheological. In addition, the mechanical properties showed a plasticizing effect of the CA at high concentrations. This research demonstrated that chemorheology is a valuable tool in the study of starch cross-linking, which becomes a promising technique to evaluate the cross-linking of other polysaccharides and cross-linking agents.

Analysis of Walking Economy after Sleeve Gastrectomy in Patients with Severe Obesity.

BACKGROUND: Obesity is associated with a higher energy cost of walking which affects activities of daily living. Bariatric surgery with sleeve gastrectomy (SG) has beneficial effects on weight loss and comorbidities. PURPOSE: The aim of this study was to analyze the impact of SG on walking economy in subjects with severe obesity. METHODS: This observational cohort study included all patients with morbid obesity who were considered suitable candidates for SG between June 2017 and June 2019. Each patient underwent an incremental cardiopulmonary exercise test on a treadmill (modified Bruce protocol) one month before and six months after SG. Data on the energy cost of walking were recorded during three protocol stages (stage 0-slow flat walking: speed 2.7 km/h, slope 0%; stage ½-slow uphill walking: speed 2.7 km/h, slope 5%; stage 1-fast uphill walking: speed 4.0 km/h, slope 8%). RESULTS: 139 patients with morbid obesity (78% women; age 44.1 ± 10.7 years; BMI 42.5 ± 4.7 kg/m2) were included in the study. At six months post-SG, patients presented with a significantly decreased body weight (-30.5 ± 17.2 kg; p < 0.05), leading to an average BMI of 31.6 ± 4.2 kg/m2. The net energy cost of walking (measured in J/m and J/kg/m) of the subjects was lower compared to pre-SG at all three protocol stages. This improvement was also confirmed when the subjects were grouped by gender and obesity classes. CONCLUSION: After a significant weight loss induced by SG, regardless of the severity of obesity and gender, patients exhibited a lower energy expenditure and an improved walking economy. These changes make it easier to perform daily routines and may facilitate an increase in physical activity.

Beyond Weight Loss: Added Benefits Could Guide the Choice of Anti-Obesity Medications.

PURPOSE OF REVIEW: To highlight the added benefits of approved and upcoming, centrally-acting, anti-obesity drugs, focusing not only on the most common metabolic and cardiovascular effects but also on their less explored clinical benefits and drawbacks, in order to provide clinicians with a tool for more comprehensive, pharmacological management of obesity. RECENT FINDINGS: Obesity is increasingly prevalent worldwide and has become a challenge for healthcare systems and societies. Reduced life expectancy and cardiometabolic complications are some of the consequences of this complex disease. Recent insights into the pathophysiology of obesity have led to the development of several promising pharmacologic targets, so that even more effective drugs are on the horizon. The perspective of having a wider range of treatments increases the chance to personalize therapy. This primarily has the potential to take advantage of the long-term use of anti-obesity medication for safe, effective and sustainable weight loss, and to concomitantly address obesity complications/comorbidities when already established. The evolving scenario of the availability of anti-obesity drugs and the increasing knowledge of their added effects on obesity complications will allow clinicians to move into a new era of precision medicine.

Hematopoietic Stem Cells and Metabolic Deterioration in Alström Syndrome, a Rare Genetic Model of the Metabolic Syndrome.

Alström syndrome (AS) is a rare genetic disease caused by ALMS1 mutations, characterized by short stature, and vision and hearing loss. Patients with AS develop the metabolic syndrome, long-term organ complications, and die prematurely. We explored the association between AS and a shortage of hematopoietic stem/progenitor cells (HSPCs), which is linked to metabolic diseases and predicts diabetic complications. We included patients with AS at a national referral center. We measured HSPCs with flow cytometry at baseline and follow-up. We followed patients up to January 2022 for metabolic worsening and end-organ damage. We evaluated HSPC levels and mobilization as well as bone marrow histology in a murine model of AS. In 23 patients with AS, we found significantly lower circulating HSPCs than in healthy blood donors (-40%; P = .002) and age/sex-matched patients (-25%; P = .022). Longitudinally, HSPCs significantly declined by a further 20% in patients with AS over a median of 36 months (interquartile range 30-44). Patients with AS who displayed metabolic deterioration over 5.3 years had lower levels of HSPCs, both at baseline and at last observation, than those who did not deteriorate. Alms1-mutated mice were obese and insulin resistant and displayed significantly reduced circulating HSPCs, despite no overt hematological abnormality. Contrary to what was observed in diabetic mice, HSPC mobilization and bone marrow structure were unaffected. We found depletion of HSPCs in patients with AS, which was recapitulated in Alms1-mutated mice. Larger and longer studies will be needed to establish HSPCs shortage as a driver of metabolic deterioration leading to end-organ damage in AS.