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Obesity is a systemic disease frequently associated with important complications such as type 2 diabetes and cardiovascular diseases. It has also been proven that obesity is a disease associated with chronic low-grade systemic inflammation and that weight loss improves this low-grade chronic inflammatory condition. The P2X7 purinergic receptor (P2X7R), belonging to the family of the receptors for extracellular ATP, is a main player in inflammation, activating inflammasome and pro-inflammatory cytokine production. In this study, we evaluated the plasma levels of soluble P2X7R (sP2X7R) measured in a group of obese patients before and one year after bariatric surgery. Furthermore, we evaluated the relation of sP2X7R to inflammatory marker plasma levels. We enrolled 15 obese patients who underwent laparoscopic sleeve gastrectomy, evaluating anthropometric parameters (weight, height, BMI and waist circumference) before and after surgery. Moreover, we measured the plasma levels of inflammatory markers (CRP, TNFα and IL-6) before and after weight loss via bariatric surgery. The results of our study show that one year after bariatric surgery, obese patients significantly decrease body weight with a significant decrease in CRP, TNF-alfa and IL-6 plasma levels. Similarly, after weight loss, obese subjects showed a significant reduction in sP2X7R plasma levels. Moreover, before surgery, plasma levels of sP2X7R were inversely related with those of CRP, TNF-alfa and IL-6. Given the role of P2X7R in inflammation, we hypothesized that, in obese subjects, sP2X7R could represent a possible marker of chronic low-grade inflammation, hypothesizing a possible role as a mediator of obesity complications.
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Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Obesidade Mórbida , Humanos , Receptores Purinérgicos P2X7 , Diabetes Mellitus Tipo 2/complicações , Interleucina-6 , Obesidade/cirurgia , Obesidade/complicações , Cirurgia Bariátrica/métodos , Inflamação/complicações , Redução de PesoRESUMO
Background and Objectives: Bariatric surgery is the gold standard for the treatment of morbid obesity, and current evidence suggests that patients undergoing surgery can show changes in their sense of taste and smell. However, no definitive conclusions can be drawn given the heterogeneity of the studies and the contrasting results reported in the literature. Materials and Methods: We enrolled 18 obese patients undergoing laparoscopic sleeve gastrectomy (LSG) and 15 obese controls. At baseline (T0) and 6 months after enrollment/surgery (T1), both groups underwent Sniffin' Sticks and whole mouth test. Post-operative qualitative taste variations were also analyzed and SNOT-22, VAS for taste and smell, and MMSE were administered. Results: An improvement in the olfactory threshold was observed in the treatment group (p = 0.03) at 6 months. At multivariate analysis, the olfactory threshold differences observed correlated with MMSE (p = 0.03) and T0 gustatory identification (p = 0.01). No changes in sense of taste were observed between the two groups at 6 months, even though nine subjects in the treatment group reported a worsening of taste. This negatively correlated with age (p < 0.001), but a positive marginal correlation was observed with the olfactory threshold difference between T0 and T1 (p = 0.06). Conclusions: Olfaction can improve after LSG, and this seems to be the consequence of an improved olfactory threshold. Although we did not observe any change in gustatory identification, food's pleasantness worsened after bariatric surgery.
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Laparoscopia , Obesidade Mórbida , Gastrectomia/efeitos adversos , Humanos , Obesidade Mórbida/cirurgia , Olfato , PaladarRESUMO
BACKGROUND: 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. METHODS: 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 < 0.05 was considered statistically significant. RESULTS: The mean percent EBL was 26.54 ± 11.02 and 27.12 ± 12.35 kg/m(2) in groups with and without pouch, respectively. The mean volume of the pouch after LSG was 17.13 ± 21.56 mm(3). Pouch volume, when present, was not significantly correlated to weight loss (P = 0.88 95% CI, CL 19.88-33.20 group 2; CL 22.94-31.30 group 1). CONCLUSIONS: No statistical correlation was found between the volume of the gastric pouch and weight loss (percent EBL) after LSG in symptomatic or with unsatisfactory weight loss patients.
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Gastrectomia/métodos , Laparoscopia , Redução de Peso , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Adulto JovemRESUMO
AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS/INTERPRETATION: In mice and humans, reduced p66Shc levels protect from obesity, but not from ectopic fat accumulation, glucose intolerance and insulin resistance.
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Resistência à Insulina/genética , Obesidade/genética , Proteínas Adaptadoras da Sinalização Shc/genética , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Adiposidade/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose/genética , Glicemia/metabolismo , Dieta Hiperlipídica , Feminino , Humanos , Insulina/metabolismo , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Obesidade/metabolismo , Estresse Oxidativo/genética , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de SrcRESUMO
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.
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The aim of this study was to evaluate the safety and efficacy of the endoscopic sleeve gastroplasty (ESG) procedure. Patients ineligible for bariatric surgery due to comorbidities or low Body Mass Index (BMI) were offered ESG. Gastric tubularization was carried out via multiple multi-bite sutures across the greater curvature of the stomach. The patients underwent a water-soluble swallow test on post-operative day 1 (POD-1) to assess gastric emptying and were placed on a soft diet if upper GI tract function was confirmed. From January 2019 to March 2022, 27 patients underwent ESG: 14 for severe obesity with comorbidities, including liver transplant, end-stage kidney disease, severe cardiovascular and respiratory diseases. The mean BMI before treatment was 36 ± 9 kg/m2. Two patients (7%) who developed gastric bleeding were successfully treated with packed red blood cells (PRBC) transfusions. After a mean follow-up of 18 months, the percentage of total body weight loss (%TBWL) and the percentage of excess weight (%EWL) were 11 ± 7 and 39 ± 27, respectively. The latter was significantly higher in the patients with an initial BMI < 40 kg/m2 (50 vs 22, p < 0.05). The patients whose gastric sleeve extended for more than a third of the length of the stomach (p < 0.05) had better results. ESG was found to be effective and safe in high-risk surgical patients whose initial BMI was (< 40). Studies characterized by larger number of patients and longer follow-up periods will be able to confirm these results.
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Gastroplastia , Humanos , Gastroplastia/efeitos adversos , Obesidade/cirurgia , Resultado do Tratamento , Redução de Peso , Índice de Massa CorporalRESUMO
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 < 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 < 0.001), Δ low density lipoprotein-cholesterol values (p < 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.
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Gastrectomia/métodos , Derivação Gástrica/métodos , Lipídeos/sangue , Obesidade Mórbida/sangue , Adolescente , Adulto , Idoso , Antropometria , Índice de Massa Corporal , Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Período Pós-Operatório , Resultado do Tratamento , Triglicerídeos/sangue , Redução de Peso , Adulto JovemRESUMO
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.
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Laparoscopia , Obesidade , Fenômenos Biomecânicos , Gastrectomia , Humanos , Obesidade/cirurgia , Estômago , Resultado do Tratamento , Redução de PesoRESUMO
Systemic diseases affect multiple tissues that interact with each other within a network difficult to explore at the body level. However, understanding the interdependences between tissues could be of high relevance for drug target identification, especially at the first stages of disease development. In vitro systems have the advantages of accessibility to measurements and precise controllability of culture conditions, but currently have limitations in mimicking human in vivo systemic tissue response. In this work, we present an in vitro model of cross-talk between an ex vivo culture of adipose tissue from an obese donor and a skeletal muscle in vitro model from a healthy donor. This is relevant to understand type 2 diabetes mellitus pathogenesis, as obesity is one of its main risk factors. The human adipose tissue biopsy was maintained as a three-dimensional culture for 48 h. Its conditioned culture medium was used to stimulate a human skeletal muscle-on-chip, developed by differentiating primary cells of a patient's biopsy under topological cues and molecular self-regulation. This system has been characterized to demonstrate its ability to mimic important features of the normal skeletal muscle response in vivo. We then found that the conditioned medium from a diseased adipose tissue is able to perturb the normal insulin sensitivity of a healthy skeletal muscle, as reported in the early stages of diabetes onset. In perspective, this work represents an important step toward the development of technological platforms that allow to study and dissect the systemic interaction between unhealthy and healthy tissues in vitro. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2766, 2019.
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Tecido Adiposo/citologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , HumanosRESUMO
Determinants of resting energy expenditure (REE) in humans are still under investigation, especially the association with insulin resistance. Brown adipose tissue (AT) regulates energy expenditure through the activity of the uncoupling protein 1 (UCP1). White AT browning is the process by which some adipocytes within AT depots acquire properties of brown adipocytes ("brite" adipocytes) and it correlates with metabolic improvement. We analyzed determinants of REE in patients with obesity and assessed UCP1 expression as a "brite" marker in abdominal subcutaneous AT (SAT) and visceral omental AT (VAT). Clinical data, REE, free fat mass (FFM), and fat mass (FM) were determined in 209 patients with obesity. UCP1, PPARG coactivator 1 alpha (PPARGC1A), transcription factor A, mitochondrial (TFAM), T-box transcription factor 1 (TBX1), and solute carrier family 27 member 1 (SLC27A1) expression was assayed in SAT and VAT samples, obtained during sleeve gastrectomy from 62 patients with obesity. REE and body composition data were also available for a subgroup of 35 of whom. In 209 patients with obesity a multiple regression model was computed with REE as the dependent variable and sex, waist, FFM, FM, homeostasis model assessment-insulin resistance (HOMA), interleukin-6 and High Density Lipoprotein-cholesterol as the independent variables. Only FFM, FM and HOMA were independently correlated with REE (r = 0.787, AdjRsqr = 0.602). In each patient VAT displayed a higher UCP1, PPARGC1A, TFAM, TBX1, and SLC27A1 expression than SAT and UCP1 expression in VAT (UCP1-VAT) correlated with Body Mass Index (BMI) (r = 0.287, p < 0.05). Introducing UCP1-VAT in the multivariate model, we showed that FFM, HOMA, interleukin-6, High Density Lipoprotein-cholesterol, and UCP1-VAT were independent factors correlated with REE (r = 0.736, AdjRsqr = 0.612). We confirmed that REE correlates with FFM, FM and HOMA in a large cohort of patients. Our results clearly showed that UCP1-VAT expression was significantly increased in severe human obesity (BMI > 50 kg/m2) and that it behaved as an independent predictor of REE. Lastly, we suggest that an increased REE and browning in metabolically complicated severe obesity could represent an effort to counteract further weight gain.
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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.
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Antígenos de Neoplasias/imunologia , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Imunoglobulina M/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Obesidade/sangue , Estado Pré-Diabético/sangue , Serpinas/imunologia , Adulto , Antígenos de Neoplasias/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/cirurgia , Feminino , Seguimentos , Gastrectomia/métodos , Gastrectomia/reabilitação , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/cirurgia , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/cirurgia , Obesidade Mórbida/sangue , Obesidade Mórbida/complicações , Obesidade Mórbida/diagnóstico , Obesidade Mórbida/cirurgia , Estado Pré-Diabético/complicações , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/cirurgia , Prognóstico , Fatores de Risco , Serpinas/sangue , Resultado do Tratamento , Redução de PesoRESUMO
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.
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Gordura Abdominal/patologia , Diabetes Mellitus Tipo 2/patologia , Glucose/metabolismo , Obesidade/patologia , Gordura Subcutânea/patologia , Gordura Abdominal/metabolismo , Adulto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Gordura Subcutânea/metabolismoRESUMO
BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) slippage with pouch dilation is one the most serious long-term complications and requires reoperation in most cases. It is still controversial whether banding should be offered again or a different procedure should be chosen. We report the results of synchronous de-rebanding on a prospective series of patients treated at our institution for slippage with pouch dilation. METHODS: From January 2000 to May 2007, 29 consecutive patients underwent laparoscopic de-rebanding for slippage with pouch dilation. The mean age at primary operation was 38.9 +/- 8.2 years and the mean BMI was 46.4 +/- 8 kg/m(2). Twenty-eight had previous LAGB, while one had previous open gastric banding, the perigastric technique being used at that time. All the redo procedures were successfully carried out under laparoscopy, via the pars flaccida technique, and all the patients were followed-up according to the usual schedule. RESULTS: The mean time from the original LAGB was 45.3 +/- 30.3 months, and the mean follow-up after rebanding was 26.9 +/- 20.6 months. At rebanding, the mean BMI was 34.3 +/- 7.6, percent excess weight loss (%EWL) 54.5 +/- 31, and percent excess BMI loss (%EBL) 58.3 +/- 33, respectively. After 1 year, BMI was 36.3 +/- 7.9, %EWL 40.8 +/- 30.5, and %EBL 43.9 +/- 32.7, respectively. After 2 years, BMI was 37.13 +/- 7.4, %EWL 36.9 +/- 29.4, and %EBL 39.6 +/- 31.6, respectively, and after 3 years, BMI was 33.5 +/- 5.6, %EWL 51.9 +/- 24.3, and %EBL 55.7 +/- 25.7, respectively. One patient had re-rebanding after 6 months for a new slippage, two had band removal with refusal to switch to another procedure, one had biliopancreatic diversion for slippage recurrence, and one underwent sleeve gastrectomy for insufficient weight loss after 6 months. CONCLUSIONS: Although this is a limited series, our results show that good outcomes can be expected after rebanding in properly assessed patients with slippage and pouch dilation. Larger series and longer follow-up are needed to confirm these findings.
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Dilatação Gástrica/etiologia , Dilatação Gástrica/cirurgia , Gastroplastia/efeitos adversos , Gastroplastia/instrumentação , Laparoscopia , Obesidade Mórbida/cirurgia , Adulto , Estudos de Coortes , Remoção de Dispositivo , Falha de Equipamento , Feminino , Dilatação Gástrica/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: 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). METHODS: 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). RESULTS: 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 < 0.001) and metabolic adaptation, calculated as the difference between observed and predicted post-weight loss REE, was - 199 ± 238 kcal/day. The post-surgery level of metabolic adaptation was inversely related to postoperative percent weight loss (r = - 0.170; P < 0.05) and FM loss (r = - 0.245; P < 0.01). CONCLUSIONS: A significant reduction of resting energy expenditure and a significant degree of metabolic adaptation both occur after sleeve gastrectomy. A greater metabolic adaptation could be partly responsible for a lower weight loss after surgery.
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Adaptação Fisiológica , Cirurgia Bariátrica/estatística & dados numéricos , Metabolismo Energético , Gastrectomia/estatística & dados numéricos , Obesidade Mórbida/cirurgia , Adulto , Composição Corporal , Restrição Calórica , Calorimetria Indireta , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/cirurgia , Obesidade Mórbida/metabolismo , Descanso , Redução de PesoRESUMO
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.
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Proteína ADAMTS13/imunologia , Autoanticorpos/sangue , Coagulação Sanguínea/fisiologia , Inflamação/imunologia , Obesidade/imunologia , Redução de Peso/fisiologia , Adulto , Feminino , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangueRESUMO
INTRODUCTION: Hypoglycemia is a known adverse event following gastric bypass. The incidence of hypoglycemia after laparoscopic sleeve gastrectomy (LSG) is still under investigation. The aim of our study was to verify the presence of oral glucose tolerance test (OGTT)-related hypoglycemia after LSG and to identify any baseline predictors of its occurrence. METHODS: We analyzed 197 consecutive non-diabetic morbid obese patients that underwent LSG. All patients were studied before and 12 months after LSG. Evaluation included anthropometric parameters, 3-h OGTT for blood glucose (BG), insulin and c-peptide, lipid profile, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), highly sensitive C-reactive protein (hsCRP), and leptin. Hypoglycemia was defined as BG ≤ 2.7 mmol/l. RESULTS: After surgery, 180 patients completed the OGTT. Eleven patients did not complete the test for gastric intolerance, and in six patients, the test was stopped earlier for the onset of severe symptomatic hypoglycemia. Of the patients, 61/186 (32.8%) had at least one OGTT-related hypoglycemia. The highest frequency of hypoglycemic events occurred 150' after glucose load (20.2%). At baseline, patients with hypoglycemic events after surgery (Hypo) were younger (40 ± 11 vs 46 ± 10 years; p < 0.001), less obese (BMI 46 ± 5.7 vs 48.4 ± 7.9 kg/m2; p < 0.05), and had a worse lipid profile as compared to patients without hypoglycemic events (N-Hypo). Moreover, after LSG, Hypo patients compared with N-Hypo presented a higher weight loss (%EBMIL 80 ± 20 vs 62 ± 21%; p < 0.001). Low age, low fasting glucose, and high triglyceride levels before LSG were independent predictors of hypoglycemia development after surgery (r 2 = 0.131). CONCLUSION: These findings confirm the high incidence of post-prandial hypoglycemia 1 year after LSG. Hypoglycemia is more frequent in younger patients with lower fasting glucose and higher triglyceride levels before surgery.
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Gastrectomia/efeitos adversos , Hipoglicemia/diagnóstico , Hipoglicemia/epidemiologia , Hipoglicemia/etiologia , Obesidade Mórbida/cirurgia , Adulto , Glicemia/metabolismo , Jejum/sangue , Feminino , Seguimentos , Gastrectomia/métodos , Teste de Tolerância a Glucose , Humanos , Hipoglicemia/sangue , Incidência , Insulina/sangue , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Obesidade Mórbida/epidemiologia , Prognóstico , Fatores de RiscoRESUMO
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.
Assuntos
Adipócitos/patologia , Caseína Quinase II/metabolismo , Insulina/metabolismo , Obesidade/metabolismo , Obesidade/patologia , Transdução de Sinais , Regulação para Cima , Células 3T3-L1 , Tecido Adiposo Branco/patologia , Animais , Transporte Biológico , Glucose/metabolismo , Humanos , Fígado/metabolismo , Camundongos , Músculo Esquelético/metabolismoRESUMO
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.
Assuntos
Tecido Adiposo/fisiologia , Micropartículas Derivadas de Células/fisiologia , Redução de Peso/fisiologia , Adulto , Coagulação Sanguínea/fisiologia , Índice de Massa Corporal , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/fisiopatologia , Estudos ProspectivosRESUMO
BACKGROUND: Liver metastases represent the major determinant of survival in patients with colorectal cancer (CRC). In cases with unresectable liver disease, more effective agents are needed, since chemotherapy achieves median survival of only 15 months. Protein kinases coordinate complex functions that are often disregulated in cancer and are therefore considered important targets for molecular therapeutics. In this study, we investigated the phosphoproteomic status of different protein kinases in primary CRC and in liver metastases. METHODS: The status of 29 key endpoints was evaluated using reverse phase protein array on laser capture microdissected neoplastic cells from five primary CRCs without metastases, three patient-matched primary CRCs and synchronous liver metastases and five CRC metachronous liver metastases. RESULTS: Unsupervised hierarchical two-way clustering analysis showed an entirely different phosphoproteomic profile in primary CRCs compared to liver metastases. This difference was observed also in primary and metastatic patient-matched lesions. CONCLUSIONS: Our findings of different signaling pathways between primary and metastatic CRC suggest a possible microenvironment effect, and emphasize the need to perform molecular network analysis of metastatic tissue when molecular targeting is considered.
Assuntos
Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Fosfotransferases/metabolismo , Análise Serial de Proteínas , Análise por Conglomerados , Neoplasias do Colo/genética , Humanos , Neoplasias Hepáticas/genética , Especificidade por SubstratoRESUMO
BACKGROUND: Laparoscopic greater curvature plication (LGCP) and laparoscopic sleeve gastrectomy (LSG) both reduce gastric capacity, either by in-folding (LGCP) or removing (LSG) the greater curvature. While mid and long-term results of LSG are well known, LGCP is still considered investigational. The aim of this study was to compare the effectiveness of LGCP and LSG in terms of weight loss and safety. METHODS: Forty-five obese LGCP patients (6 males and 39 females) were matched with 45 LSG patients. The two groups were matched according to sex, age ± 10 years and BMI ± 1 kg/m(2). Surgical complication rate, redo surgery need, excess BMI loss (%EBL) and mean BMI at 3 and 6 months were compared. RESULTS: LGCP and LSG mean age was 37.8 and 40 years, while the mean preoperative BMI was 40.65 and 41 kg/m(2), respectively. There was no difference in operative time, complication rate, mean BMI and %EBL at 3 months. Redo surgery rate was higher in LGCP group (LGCP 60 % vs LSG 8.8 %, P < 0.0001). The mean time to redo surgery was longer in LSG group (23 ± 6.61 vs 17.3 ± 7.67 months, P = 0.0003). The mean BMI at 6 months was lower in LSG group (32 ± 5.7 vs 34.6 ± 5.3, P = 0.028). The mean %EBL at 6 months was higher in LSG group (57 ± 30.89 vs 40.2 ± 25, P = 0.0057). CONCLUSIONS: LGCP patients required more redo surgery. Weight loss was greater in LSG group at 6-month follow-up.