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Insulin-like factor 5 (INSL5), a novel hormone secreted by the enteroendocrine cells of the distal colon, has been implicated in appetite and body weight regulation in animals given its orexigenic properties. We investigated basal INSL5 plasma levels in a group of morbidly obese subjects before and after laparoscopic sleeve gastrectomy. Furthermore, we analyzed the expression of INSL5 in human adipose tissue. Before bariatric surgery, obese subjects showed basal INSL5 plasma levels that were positively correlated with BMI, fat mass, and leptin plasma levels. After weight loss by laparoscopic sleeve gastrectomy, INSL5 plasma levels in obese subjects were significantly lower than those observed before surgery. Finally, we did not detect any expression of the INSL5 gene in human adipose tissue, both at the mRNA and protein levels. The present data show that subjects with obesity have INSL5 plasma levels positively correlating with adiposity markers. After bariatric surgery, INSL5 plasma levels decreased significantly, and this decrease was not directly due to the loss of adipose tissue since this tissue does not express INSL5. Considering the orexigenic properties of INSL5, the reduction of its plasma levels after bariatric surgery in obese subjects could participate in the still unclear mechanisms leading to appetite reduction that characterize bariatric surgery procedures.

The mechanical characterization of adipose tissues is important for various medical purposes, including plastic surgery and biomechanical applications, such as computational human body models for the simulation of surgical procedures or injury prediction, for example, in the evaluation of vehicle crashworthiness. In this context, the measurement of human subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) mechanical properties in relation to subject characteristics may be really relevant. The aim of this work was to properly characterize the mechanical response of adipose tissues in patients with obesity. Then, the data were exploited to develop a reliable finite element model of the adipose tissues characterized by a constitutive material model that accounted for nonlinear elasticity and time dependence. Mechanical tests have been performed on both SAT and VAT specimens, which have been harvested from patients with severe obesity during standard laparoscopic sleeve gastrectomy intervention. The experimental campaign included indentation tests, which permitted us to obtain the initial/final indentation stiffnesses for each specimen. Statistical results revealed a higher statistical stiffness in SAT than in VAT, with an initial/final indentation stiffness of 1.65 (SD ± 0.29) N/30.30 (SD ± 20) N compared to 1.29 (SD ± 0.30) N/21.00 (SD ± 16) N. Moreover, the results showed that gender, BMI, and age did not significantly affect the stiffness. The experimental results were used in the identification of the constitutive parameters to be inserted in the constitutive material model. Such constitutive characterization of VAT and SAT mechanics can be the starting point for the future development of more accurate computational models of the human adipose tissue and, in general, of the human body for the optimization of numerous medical and biomechanical procedures and applications.

Although obesity represents a risk factor for the development of type 2 diabetes mellitus (T2DM), the link between these pathological conditions is not so clear. The manner in which the different elements of adipose tissue (AT) interplay in order to grow has been suggested to have a role in the genesis of metabolic complications, but this has not yet been fully addressed in humans. Through IHC, transmission electron microscopy, cytometry, and in vitro cultures, we described the morphological and functional changes of subcutaneous and visceral AT (SAT and VAT) in normoglycemic, prediabetic and T2DM patients with obesity compared to lean subjects. In both SAT and VAT we measured a hypertrophic and hyperplastic expansion, causing similar vascular rarefaction in obese patients with different degrees of metabolic complications. Capillaries display dysfunctional basement membrane thickening only in T2DM patients evidencing VAT as a new target of T2DM microangiopathy. The largest increase in adipocyte size and decrease in adipose stem cell number and adipogenic potential occur both in T2DM and in prediabetes. We showed that SAT and VAT remodeling with stemness deficit is associated with early glucose metabolism impairment suggesting the benefit of an AT-target therapy controlling hypertrophy and hyperplasia already in prediabetic obese patients.

Fewer studies compared the improvement of plasma lipid levels after different types of surgery, in particular compared to one-anastomosis gastric bypass (OAGB). The aim of our study was to investigate how laparoscopic sleeve gastrectomy (LSG) and OAGB impact on weight loss and lipid profile 18 months after surgery, in patients with severe obesity. Forty-six patients treated with OAGB were matched to eighty-eight patients submitted to LSG. Weight loss after OAGB (33.2%) was more evident than after LSG (29.6%) (p = 0.024). The difference in the prevalence of dyslipidemia showed a statistically significant reduction only after OAGB (61% versus 22%, p &lt, 0.001). After adjustment for delta body mass index (BMI), age and sex, we demonstrated a statistically significant decrease of the differences between the changes before and after (delta Δ) the two surgery procedures: Δ total cholesterol values (p &lt, 0.001), Δ low density lipoprotein-cholesterol values (p &lt, 0.001) and Δ triglycerides values (p = 0.007). Patients with severe obesity undergoing to OAGB presented a better improvement of lipid plasma values than LSG patients. The reduction of lipid plasma levels was independent of the significant decrease of BMI after surgery, of age and of sex.

Obese patients have been described at increased risk of thrombotic thrombocytopenic purpura, a disease caused by anti-ADAMTS13 autoantibodies. ADAMTS13 has a structure homology with the adipokine thrombospondin-1. We previously demonstrated an increased presence of anti-ADAMTS13 antibodies in obese patients. We aimed to study the changes induced by weight loss after bariatric surgery on some inflammatory and coagulative parameters and their link with anti-ADAMTS13 autoantibodies. We studied 100 obese patients before and after weight loss induced by bariatric surgery and 79 lean volunteers as controls. We measured anthropometric, metabolic and inflammatory parameters, thrombospondin-1, ADAMTS13 activity, anti-ADAMTS13 autoantibodies, Von Willebrand factor. At baseline, 13 % of patients was positive for anti-ADAMTS13 autoantibodies, while all controls were negative. Thrombospondin-1 levels were higher in obese subjects with than without antibodies, with a positive correlation between the two parameters. In multiple logistic regression analysis only thrombospondin-1 levels predicted positivity for anti-ADAMTS13 antibodies. After weight loss both anti-ADAMTS13 antibodies and thrombospondin-1 reduced significantly. Weight loss in obesity improves the inflammatory and coagulative profile, and in particular anti-ADAMTS13 autoantibodies, ADAMTS13 activity and thrombospondin-1.

Even though bariatric surgery is one of the most effective treatment option of obesity, post-surgical weight loss is not always ensured, especially in the long term, when many patients experience weight regain. Bariatric procedures are largely based on surgeon's expertise and intra-operative decisions, while an integrated in-silico approach could support surgical activity. The effects of bariatric surgery on gastric distension, which activates the neural circuitry promoting satiety, can be considered one of the main factors in the operation success. This aspect can be investigated trough computational modelling based on the mechanical properties of stomach tissues and structure. Mechanical tests on gastric tissues and structure from people with obesity are carried out, as basis for the development of a computational model. The samples are obtained from stomach residuals explanted during laparoscopic sleeve gastrectomy interventions. Uniaxial tensile and stress relaxation tests are performed in different directions and inflation tests are carried out on the entire stomach residual. Experimental results show anisotropic, non-linear elastic and time-dependent behavior. In addition, the mechanical properties demonstrate to be dependent on the sample location within the stomach. Inflation tests confirm the characteristics of time-dependence and non-linear elasticity of the stomach wall. Experimental activities developed provide a unique set of data about the mechanical behavior of the stomach of patients with obesity, considering both tissues and structure. This data set can be adopted for the development of computational models of the stomach, as support to the rational investigation of biomechanical aspects of bariatric surgery.

Background: Non-alcoholic fatty liver disease (NAFLD) has a high prevalence in obesity and its presence should be screened. Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for obesity, but its effects on NAFLD are still to be firmly established. The diagnosis of non-alcoholic steatohepatitis (NASH) is currently performed by liver biopsy, a costly and invasive procedure. Squamous cell carcinoma antigen-IgM (SCCA-IgM) is a biomarker of viral hepatitis to hepatocellular carcinoma development and its role in NAFLD to NASH progression has not yet been investigated. Objective: The aim of this study was to evaluate SCCA-IgM as a non-invasive biomarker of NAFLD/NASH in patients with different degrees of metabolic-complicated obesity before and after LSG. Method: Fifty-six patients with obesity were studied before and 12 months after LSG; anthropometric, biochemical, clinical, and imaging data were collected. Results: At baseline steatosis was strongly associated with the glycaemic profile (p = 0.016) and was already present in prediabetic patients with obesity (82%). Only 3 patients had an SCCA-IgM level above the normal cut-off. SCCA-IgM titre did not change according to glycaemic profile or steatosis. Metabolic and inflammatory factors and transaminases significantly reduced after LSG-induced weight loss, except for SCCA-IgM. The ALT/AST ratio decreased post-LSG correlated with BMI (r = 0.297, p = 0.031), insulin (r = 0.354, p = 0.014), and triglycerides (r = 0.355, p = 0.009) reduction. Conclusions: Our results confirm the tight link between NAFLD and metabolic complications, suggesting prediabetes as a new risk factor of steatosis. SCCA-IgM does not seem to have a role in the identification and prognosis of NAFLD.

Resting energy expenditure (REE) declines more than what is expected according to body composition changes after caloric restriction. This metabolic adaptation is considered one of the factors favoring weight regain. The aim of this study is to evaluate the changes of REE and calculate the degree of metabolic adaptation occurring after laparoscopic sleeve gastrectomy (LSG). REE (by indirect calorimetry) and body composition (fat-free mass or FFM, fat mass or FM by bioelectrical impedance analysis) were determined before and after 12 months in 154 patients with obesity treated with laparoscopic sleeve gastrectomy (LSG). Weight loss was 29.8 ± 10.6%, with corresponding relative reductions in FM (44.5 ± 22.8%), FFM (13.7 ± 9.9%), and REE (27.3 ± 12.9%). A predictive equation for REE was computed by using the baseline FFM and FM values to account for body composition changes. A predicted post-weight loss REE was calculated by using this equation and entering post-weight loss body composition values. Observed post-surgery REE was significantly lower than predicted one (1410 ± 312 vs 1611 ± 340 kcal/day, P

A definitive relationship between adiposity and MP production is yet to be demonstrated. The aim of our study was to prospectively evaluate the levels of microparticles (MP) in a group of 20 III degree obese patients before and after weight loss. Plasma levels of annexin V-MP, endothelial-derived MP, platelet-derived MP (CD61+ and P-Selectin+), leukocyte-derived MP, tissue factor-bearing (TF+) and CD36+MP were prospectively measured in 20 patients with III degree obesity (BMI ≥ 40 kg/m(2)) before (T0) and 3 (T3) and 12 (T12) months after sleeve gastrectomy (SLG). Obese patients had lost 18 % of their body weight at T3 and 41 % at T12. We find that considering all MP, except for endothelial-derived MP, which had significantly decreased at T3, all MP subtypes had significantly decreased at T12. At T12, subjects showed a higher median level of all types of MP, except endothelial-derived MP, compared to T3, but without a statistically significant difference. The percentages of reduction of all the MP were significantly correlated with the percentage of reduction of BMI. The reductions of leukocyte-derived, TF+ and CD36+MP were significantly correlated with the reduction of leptin. Moreover, the reductions of leukocyte-derived and CD36+MP were significantly correlated with hs-CRP decrease. The decrease of BMI post-SLG in morbid obesity was matched with a decrease of circulating MP of endothelial, platelet, leukocyte origin, TF+ and CD36+. A trend of slight increase in all MP subtypes, except endothelial-derived, was detected 12 months after gastrectomy, indicating a possible underlying slow low-grade inflammatory/hypercoagulability state from adipose tissue before the potential overt weight gain.

Laparoscopic sleeve gastrectomy (LSG) is considered safe and effective even as conversion procedure after primary bariatric operations. The correlation between gastric pouch volumes and patients weight loss remains unclear. To assess a correlation between the gastric remnant size and the weight loss, we reviewed 49 consecutive barium swallow UGS performed at our institute from August 2012 through May 2014 in LSG patients with symptoms and/or unsatisfactory weight loss. The anteroposterior (AP), laterolateral (LL) and vertical (CC) diameters of the gastric pouch were measured to calculate the volume by the formula of the ellipsoid (AP × LL × CC × 0.5). Patients were divided in two groups: group 1 without gastric pouch (n = 36) and group 2 with gastric pouch (n = 13). Correlation between pouch volume and weight loss data was calculated with t Student’s and Fisher tests to compare the percent excess body mass index (BMI) and percent excess body mass loss (EBL) between two groups, and P

Insulin plays a major role in glucose metabolism and insulin-signaling defects are present in obesity and diabetes. CK2 is a pleiotropic protein kinase implicated in fundamental cellular pathways and abnormally elevated in tumors. Here we report that in human and murine adipocytes CK2-inhibition decreases the insulin-induced glucose-uptake by counteracting Akt-signaling and GLUT4-translocation to the plasma membrane. In mice CK2 acts on insulin-signaling in adipose tissue, liver and skeletal muscle and its acute inhibition impairs glucose tolerance. Notably, CK2 protein-level and activity are greatly up-regulated in white adipose tissue from ob/ob and db/db mice as well as from obese patients, regardless the severity of their insulin-resistance and the presence of pre-diabetes or overt type 2 diabetes. Weight loss obtained by both bariatric surgery or hypocaloric diet reverts CK2 hyper-activation to normal level. Our data suggest a central role of CK2 in insulin-sensitivity, glucose homeostasis and adipose tissue remodeling. CK2 up-regulation is identified as a hallmark of adipose tissue pathological expansion, suggesting a new potential therapeutic target for human obesity.

Oxygen radicals generated by p66Shc drive adipogenesis, but contradictory data exist on the role of p66Shc in the development of obesity and the metabolic syndrome. We herein explored the relationships among p66Shc, adipose tissue remodelling and glucose metabolism using mouse models and human adipose tissue samples.In wild-type (WT), leptin-deficient (ob/ob), p66Shc(-/-) and p66Shc(-/-) ob/ob mice up to 30 weeks of age, we analysed body weight, subcutaneous and visceral adipose tissue histopathology, glucose tolerance and insulin sensitivity, and liver and muscle fat accumulation. A group of mice on a high fat diet (HFD) was also analysed. A parallel study was conducted on adipose tissue collected from patients undergoing elective surgery.We found that p66Shc(-/-) mice were slightly leaner than WT mice, and p66Shc(-/-) ob/ob mice became less obese than ob/ob mice. Despite their lower body weight, p66Shc(-/-) mice accumulated ectopic fat in the liver and muscles, and were glucose intolerant and insulin resistant. Features of adverse adipose tissue remodelling induced by obesity, including adipocyte enlargement, apoptosis, inflammation and perfusion were modestly and transiently improved by p66Shc (also known as Shc1) deletion. After 12 weeks of the HFD, p66Shc(-/-) mice were leaner than but equally glucose intolerant and insulin resistant compared with WT mice. In 77 patients, we found a direct correlation between BMI and p66Shc protein levels. Patients with low p66Shc levels were less obese, but were not protected from other metabolic syndrome features (diabetes, dyslipidaemia and hypertension).In mice and humans, reduced p66Shc levels protect from obesity, but not from ectopic fat accumulation, glucose intolerance and insulin resistance.

Laparoscopic sleeve gastrectomy (LSG) is now considered an effective bariatric procedure (American Society for Metabolic and Bariatric Surgery statement). We attempted to assess the size of the gastric fundus remaining after LSG and gastric voiding rate (fast/slow) by radiological upper gastrointestinal series (UGS) with a water-soluble contrast medium (CM). The findings were compared with weight loss data. Seventy-four obese patients underwent LSG. Radiological UGS were used to measure the remaining fundus size in 28 of 74 patients 24–72 h after the procedure, with the aid of Matlab software and a library image processing toolbox (MathWorks®). Sleeve voiding was measured in 57 of 74 patients, based on the patients’ radiological reports. The mean volume of the remaining fundus was 17.56 ml (range 1.00–77.03 ml). The mean percent excess BMI loss (%EBL) was 39.5%, 53.7%, and 60.8%, respectively, 3, 6, and 12 months after LSG. Sleeve voiding was fast in 49 of 57 patients (85.96%) and slow in eight (14.03%). No correlation was found between the estimated volume of the remaining gastric fundus and weight loss (%EBL) after LSG. Patients showing a rapid gastroduodenal transit of the CM achieved a better weight loss than patients with a slow voiding rate.