RESUMO
Objective: Preoperative upper gastrointestinal endoscopy (UGIE) and postoperative histopathological examination (HPE) of resected specimens are still controversial issues in bariatric surgery. Methods: A retrospective review of prospectively collected laparoscopic sleeve gastrectomies (SG) performed at our institution for morbid obesity was carried out. All patients underwent pre-operative UGIE with biopsy, post-operative HPE and conventional post-operative follow-up. Results: From January 2019 through January 2021 we performed a total of 501 laparoscopic SG. A total of 12 (2.4%) neoplasms were found, 2 evident at preoperative UGIE, 4 detected during operation, and 6 at HPE. Eight of these 12 cases had some malignant potential and 5 would not have been detected without HPE of the specimen. The most significant unexpected case was a fundic gland type adenocarcinoma in a 64-year-old female with severe obesity. Conclusion: On the basis of our clinical experience, we recommend both preoperative endoscopic assessment and postoperative HPE of the specimen to provide the best available treatment to these patients.
Assuntos
Laparoscopia , Obesidade Mórbida , Feminino , Humanos , Pessoa de Meia-Idade , Laparoscopia/efeitos adversos , Gastrectomia/efeitos adversos , Obesidade Mórbida/cirurgia , Obesidade Mórbida/etiologia , Obesidade Mórbida/patologia , Endoscopia Gastrointestinal , Biópsia , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the incidence of corticotroph hyperplasia (CH) or lymphocyte infiltration in the pituitary of patients with obesity. METHODS: The pituitary and adrenal glands from 161 adult autopsies performed between 2010 and 2019 at our institution were reviewed. The clinical history, body mass index (BMI), and cause of death were recorded. Routine hematoxylin and eosin staining, reticulin staining, and immunohistochemical staining for adrenocorticotropic hormone, CD3, and CD20 were performed. The results were analyzed using the Fisher and chi-square statistics. Decedents were separated into 4 groups based on BMI (kg/m2): (1) lean (BMI, <25.0), (2) overweight (BMI, 25.0-29.9), (3) obesity class I (BMI, 30.0-34.9), and (4) obesity classes II to III (BMI, >34.9). RESULTS: CH/neoplasia was identified in 44 of 161 pituitary glands. Four (9.1%) of 53 lean patients had pituitary lesions, whereas 27.3% (12) of overweight, 22.7% (10) of obesity class I, and 40.9% (18) of obesity class II patients had hyperplasia (P < .0001). Small corticotroph tumors were identified in 15 patients; only 1 was a lean patient, and the tumor was associated with the Crooke hyaline change of nontumorous corticotrophs. The presence of CH and neoplasia was associated with adrenal cortical hyperplasia and lipid depletion. Microscopic foci of T and B lymphocytes were identified in the pituitaries of patients in each weight category; no independent association between BMI and lymphocyte inflammation was found. CONCLUSION: Our data indicate an association between CH/neoplasia and obesity. It remains unclear whether obesity is the cause or effect of adrenocorticotropic hormone and cortisol excess.
Assuntos
Obesidade Mórbida , Doenças da Hipófise , Neoplasias Hipofisárias , Adulto , Humanos , Corticotrofos/metabolismo , Corticotrofos/patologia , Obesidade Mórbida/patologia , Hiperplasia/patologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Hipófise/patologia , Hormônio Adrenocorticotrópico/metabolismo , Doenças da Hipófise/complicações , Doenças da Hipófise/epidemiologia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/patologia , Obesidade/complicações , Obesidade/epidemiologiaRESUMO
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the GI tract. Despite this, they rarely occur, accounting for only 1% to 3% of all gastrointestinal tumors. This report describes a 53-year-old female patient with surgical history of Roux-en-Y gastric bypass (RYGB) who presented with right upper quadrant abdominal pain. CT imaging revealed a large 20 × 12 × 16 cm mass in the excluded stomach remnant. Ultrasound-guided biopsy confirmed this mass to be a GIST. The patient was treated surgically with exploratory laparotomy with distal pancreatectomy, partial colectomy, partial gastrectomy, and splenectomy. There are currently only 3 known reported cases of GISTs after RYGB.
Assuntos
Derivação Gástrica , Coto Gástrico , Tumores do Estroma Gastrointestinal , Obesidade Mórbida , Feminino , Humanos , Pessoa de Meia-Idade , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Tumores do Estroma Gastrointestinal/cirurgia , Tumores do Estroma Gastrointestinal/patologia , Coto Gástrico/patologia , Coto Gástrico/cirurgia , Gastrectomia/métodos , Esplenectomia , Obesidade Mórbida/cirurgia , Obesidade Mórbida/patologia , Anastomose em-Y de RouxRESUMO
BACKGROUND AND OBJECTIVE: While underlying pathophysiology linking obesity to brain health is not completely understood, white adipose tissue (WAT) is considered a key player. In obesity, WAT becomes dysregulated, showing hyperplasia, hypertrophy, and eventually inflammation. This disbalance leads to dysregulated secretion of adipokines influencing both (cardio)vascular and brain health. Within this study, we investigated the association between omental WAT (oWAT) and subcutaneous WAT (scWAT) with brain structure and perfusion and cognition in adults with severe obesity. METHODS: Within the cross-sectional BARICO study, brain structure and perfusion and cognitive function were measured before bariatric surgery (BS) using MRI and cognitive assessments. During BS, oWAT and scWAT depots were collected and analyzed by histopathology. The number and diameter of adipocytes were quantified together with the amount of crown-like structures (CLS) as an indication of inflammation. Blood samples were collected to analyze adipokines and inflammatory markers. Neuroimaging outcomes included brain volumes, cortical thickness, white matter (WM) integrity, WM hyperintensities, cerebral blood flow using arterial spin labeling (ASL), and the ASL spatial coefficient of variation (sCoV), reflecting cerebrovascular health. RESULTS: Seventy-one patients were included (mean age 45.1 ± 5.8 years; 83.1% women; mean body mass index 40.8 ± 3.8 kg/m2). scWAT showed more CLS (z = -2.72, p < 0.01, r = -0.24) and hypertrophy compared with oWAT (F(1,64) = 3.99, p < 0.05, η2 = 0.06). Adiponectin levels were inversely associated with the average diameter of scWAT (ß = -0.31, 95% CI -0.54 to -0.08) and oWAT (ß = -0.33, 95% CI -0.55 to -0.09). Furthermore, the adipocyte diameter in oWAT was positively associated with the sCoV in the parietal cortex (ß = 0.33, 95% CI 0.10-0.60), and the number of adipocytes (per mm2) was positively associated with sCoV in the nucleus accumbens (NAcc) (ß = 0.34, 95% CI 0.09-0.61). Cognitive function did not correlate with any WAT parameter or plasma marker. These associations were highly influenced by age and sex. sCoV in the NAcc was positively associated with fasting plasma glucose (ß = 0.35, 95% CI 0.10-0.56). DISCUSSION: scWAT and oWAT are different in morphology and in their relationship with plasma markers and cerebrovascular health. Although scWAT showed more CLS and hypertrophy, scWAT was not associated with brain readouts. This study showed, however, important relationships between oWAT morphology and cerebrovascular health in obesity. TRIAL REGISTRATION INFORMATION: Trial Registration Number NTR7288 (trialregister.nl/trial/7090).
Assuntos
Obesidade Mórbida , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Obesidade Mórbida/complicações , Obesidade Mórbida/patologia , Obesidade Mórbida/cirurgia , Estudos Transversais , Obesidade/complicações , Obesidade/diagnóstico por imagem , Obesidade/patologia , Tecido Adiposo Branco/diagnóstico por imagem , Tecido Adiposo Branco/patologia , Tecido Adiposo/patologia , Cognição , Encéfalo/patologia , Hipertrofia/patologia , Perfusão , Inflamação/diagnóstico por imagem , Inflamação/patologia , AdipocinasRESUMO
BACKGROUND: Obesity, non-alcoholic fatty liver disease (NAFLD) and insulin resistance are three pathological conditions highly correlated, but this relationship is not fully elucidated. Hence, we aimed to assess the association of hepatic steatosis and fibrosis with different measures of insulin sensitivity in patients with severe obesity and type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study (Oseberg trial) including patients with T2DM referred for bariatric surgery at Vestfold Hospital Trust, Norway. Magnetic resonance imaging (MRI) and the enhanced liver fibrosis (ELF) test was used for estimation of liver fat fraction (LFF) and degree of fibrosis, respectively. Oral and intravenous glucose tolerance tests were applied for estimation of insulin sensitivity (HOMA2S, Matsuda ISI and MinMod SI). RESULTS: A total of 100 patients (mean [SD] age 47.5 [9.7] years, 65% women, BMI 42.0 [5.3] kg/m2 and 98% with metabolic syndrome) were included in the analyses. The mean (SD) LFF in the total population was 19.1 (11.5), and the mean (SD) ELF score was 8.46 (0.84), a value representing moderate fibrosis. LFF was inversely associated with HOMA2S and Matsuda ISI, and both measures were significantly higher in the no or low-grade steatosis group compared with the medium-to-high grade steatosis group (mean difference [95% CI] 5.9 [2.2-9.6]%, Cohen's d = 0.75), and (0.7 [0.3-1.1], Cohen's d = 0.80, respectively). There was no association between LFF, as a categorical or continuous variable, and MinMod SI. The proportions of patients with none to mild fibrosis, moderate fibrosis and severe fibrosis were 14, 78 and 6%, respectively, and there were no significant associations between level of fibrosis and measures of insulin sensitivity. CONCLUSIONS: Patients with morbid obesity and T2DM demonstrated high levels of liver fat fraction, and we showed that hepatic steatosis, but not the degree of liver fibrosis, was associated with different measures of insulin sensitivity in patients with severe obesity and T2DM. Further, our results might indicate that the LFF is primarily associated with hepatic, and not peripheral insulin sensitivity. To improve the diagnosis of NAFLD and the prediction of its progression, more studies are needed to reveal the pathological mechanistic pathways involved in NAFLD and insulin sensitivity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01778738.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade Mórbida/complicações , Obesidade Mórbida/patologia , AdultoRESUMO
Impaired mitochondrial oxidative phosphorylation (OXPHOS) in liver tissue has been hypothesised to contribute to the development of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease (NAFLD). It is unknown whether OXPHOS capacities in human visceral (VAT) and subcutaneous adipose tissue (SAT) associate with NAFLD severity and how hepatic OXPHOS responds to improvement in NAFLD. In biopsies sampled from 62 patients with obesity undergoing bariatric surgery and nine control subjects without obesity we demonstrate that OXPHOS is reduced in VAT and SAT while increased in the liver in patients with obesity when compared with control subjects without obesity, but this was independent of NAFLD severity. In repeat liver biopsy sampling in 21 patients with obesity 12 months after bariatric surgery we found increased hepatic OXPHOS capacity and mitochondrial DNA/nuclear DNA content compared with baseline. In this work we show that obesity has an opposing association with mitochondrial respiration in adipose- and liver tissue with no overall association with NAFLD severity, however, bariatric surgery increases hepatic OXPHOS and mitochondrial biogenesis.
Assuntos
Cirurgia Bariátrica , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Tecido Adiposo/patologia , Humanos , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/complicações , Obesidade/patologia , Obesidade/cirurgia , Obesidade Mórbida/complicações , Obesidade Mórbida/patologia , Obesidade Mórbida/cirurgia , Biogênese de Organelas , RespiraçãoRESUMO
ABSTRACT: We aimed to investigate the clinical feasibility of shear wave dispersion slope for assessing nonalcoholic steatohepatitis (NASH) in patients with morbid obesity before bariatric surgery.This prospective study collected data from 25 participants who received liver biopsy during bariatric surgery between February 2019 and December 2020. All participants underwent ultrasonography shear wave elastography before surgery and shear wave speed and shear wave dispersion slope were measured. Liver specimens were evaluated by 1 pathologist scored histologically for nonalcoholic fatty liver disease (NAFLD). Ultrasonography measurements were compared according to histopathologic findings. Diagnostic performance in differentiating NASH from NAFLD was evaluated using the area under the receiver operating characteristic curve (AUC). Median shear wave speed (1.48 vs 1.62 m/s, P = 0.014) and dispersion slope (8.40 vs 11.80 [m/s]/kHz, P = 0.004) were higher in NASH group than in NAFLD group. Shear wave dispersion slope tended to increase step by step as the severity of activity grade (P = 0.032) and hepatic fibrosis (P = 0.015) increased. The AUC of shear wave dispersion slope for differentiating NASH from NAFLD (AUC, 0.83; 95% confidence intervals, 0.66-1.00) was higher than that of shear wave speed (AUC, 0.78; 95% CI, 0.60-0.97), although it did not reach statistical significance (P = 0.729). Shear wave dispersion slope could be a feasible tool for assessing NASH in patients with morbid obesity.
Assuntos
Técnicas de Imagem por Elasticidade , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Técnicas de Imagem por Elasticidade/métodos , Estudos de Viabilidade , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Obesidade Mórbida/complicações , Obesidade Mórbida/patologia , Obesidade Mórbida/cirurgia , Estudos ProspectivosRESUMO
Fibrosis is the strongest predictor for disease-specific mortality in non-alcoholic fatty liver diseases (NAFLD), but the need for liver biopsy limits its diagnosis. We assessed the performance of plasma ficolin-2 (FCN-2) as a biomarker of fibrosis identified by an in silico discovery strategy. Two hundred and thirty-five morbidly obese (MO) subjects with biopsy-proven NAFLD stratified by fibrosis stage (F0, n = 44; F1, n = 134; F2, n = 46; F3/F4, n = 11) and 40 cirrhotic patients were enrolled. The cohort was subdivided into discovery (n = 76) and validation groups (n = 159). The plasma level of FCN-2 and other candidate markers was determined. FCN-2 was inversely correlated with the stage of liver fibrosis (ρ = −0.49, p < 0.001) independently of steatosis (p = 0.90), inflammation (p = 0.57), and ballooning (p = 0.59). In the global cohort, FCN-2 level decreased significantly in a stepwise fashion from F0/F1 (median 4753 ng/mL) to F2−F3−F4 (2760 ng/mL) and in cirrhotic subjects (1418 ng/mL). The diagnostic performance of FCN-2 in detecting F ≥ 2 was higher than other indexes (APRI, FIB-4) (AUROC 0.82, 0.68, and 0.6, respectively). The accuracy improved when combined with APRI score and HDL values (FCNscore, AUROC 0.85). Overall, the FCN-2 plasma level can accurately discriminate liver fibrosis status (minimal vs. moderate/advanced) significantly improving the fibrosis diagnostic algorithms.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Biomarcadores , Biópsia , Fibrose , Humanos , Lectinas , Fígado/patologia , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade Mórbida/patologia , FicolinasRESUMO
CONTEXT: Adipose tissue distribution is a key factor influencing metabolic health and risk in obesity-associated comorbidities. OBJECTIVE: Here we aim to compare the proteomic profiles of mature adipocytes from different depots. METHODS: Abdominal subcutaneous (SA) and omental visceral adipocytes (VA) were isolated from paired adipose tissue biopsies obtained during bariatric surgery on 19 severely obese women (body mass index > 30 kg/m2) and analyzed using state-of-the-art mass spectrometry. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to investigate proteome signature properties and to examine a possible association of the protein expression with the clinical data. RESULTS: We identified 3686 protein groups and found 1140 differentially expressed proteins (adj. P value < 0.05), of which 576 proteins were upregulated in SA and 564 in VA samples. We provide a global protein profile of abdominal SA and omental VA, present the most differentially expressed pathways and processes distinguishing SA from VA, and correlate them with clinical and body composition data. We show that SA are significantly more active in processes linked to vesicular transport and secretion, and to increased lipid metabolism activity. Conversely, the expression of proteins involved in the mitochondrial energy metabolism and translational or biosynthetic activity is higher in VA. CONCLUSION: Our analysis represents a valuable resource of protein expression profiles in abdominal SA and omental VA, highlighting key differences in their role in obesity.
Assuntos
Adipócitos/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade Mórbida/metabolismo , Gordura Subcutânea Abdominal/metabolismo , Adulto , Cirurgia Bariátrica , Feminino , Redes Reguladoras de Genes , Humanos , Gordura Intra-Abdominal/citologia , Gordura Intra-Abdominal/patologia , Pessoa de Meia-Idade , Obesidade Mórbida/patologia , Obesidade Mórbida/cirurgia , Omento/citologia , Omento/metabolismo , Omento/patologia , Omento/cirurgia , Proteômica , Gordura Subcutânea Abdominal/citologia , Gordura Subcutânea Abdominal/patologiaRESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), often associated with obesity and metabolic syndrome, manifests itself as steatosis, hepatic fibrosis, cirrhosis, or even end-stage liver disease. NAFLD causes inflammation, insulin resistance and cardiovascular complications. The current study aimed to evaluate the beneficial effects of bariatric surgery on biochemical parameters of hepatic functions in obese patients by comparing them before and one-year after the surgery. METHODS: A total of 72 morbidly obese patients underwent bariatric surgery between 2016 and 2018. The incidence of diabetes mellitus in this group was 29%, median body weight was 124.5 kg (109.0-140.0) and mean body mass index (BMI) was 44.38 ± 6.770 kg/m2. The used surgical procedures included gastric bypass, sleeve gastrectomy, laparoscopic gastric plication, and single anastomosis duodeno-ileal bypass-sleeve gastrectomy. Biochemical parameters including ALT/AST ratio (AAR), NAFLD fibrosis score (NFS), hepatic fibrosis index (FIB-4) and Fatty Liver Index (FLI) were evaluated in all patients at the time of surgery and one year after the intervention. RESULTS: Significant improvement after the intervention was observed in 64 patients. A significant reduction in body weight (P<0.0001), waist circumference (P<0.0001), and body mass index (P<0.0001) were observed. NAFLD liver fibrosis index changed significantly (P<0.0001), suggesting a trend of improvement from advanced fibrosis towards stages 0-2. The FIB-4 fibrosis index indicated significant improvement (P=0.0136). Besides, a significant decline in hepatic steatosis (P<0.0001) was observed after bariatric surgery as compared to the pre-surgery fatty liver conditions. CONCLUSION: Among the strategies to overcome NAFLD-associated impediments, bariatric surgery can be considered effective in reducing obesity and metabolic co-morbidities. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04569396).
Assuntos
Cirurgia Bariátrica , Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Cirurgia Bariátrica/efeitos adversos , Fibrose , Seguimentos , Humanos , Fígado , Cirrose Hepática/complicações , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/cirurgia , Obesidade Mórbida/complicações , Obesidade Mórbida/patologia , Obesidade Mórbida/cirurgia , Estudos ProspectivosRESUMO
Extracellular vesicles (EVs) have been recently postulated as key players in metabolic disorders emerging as an alternative way of paracrine/endocrine communication. However, the nature of EVs shed by adipose tissue (AT) and their role in obesity is still very limited. Here, we isolated human morbid obese visceral (VAT) and subcutaneous (SAT) whole AT shed EVs from donors submitted to bariatric surgery to characterize their protein cargo by qualitative and quantitative/SWATH mass spectrometry analysis. We identified 574 different proteins shed by morbid obese VAT and 401 proteins in those from SAT, establishing the first obese AT EV proteome reference map. Only 50% of identified proteins in VAT vesicles were common to those in SAT; additionally, EVs shed by obese VAT showed more AT and obesity-related adipokines than SAT. Functional classification shows that obese VAT vesicles exhibit an enrichment of proteins implicated in AT inflammation and insulin resistance such as TGFBI, CAVN1, CD14, mimecan, thrombospondin-1, FABP-4 or AHNAK. Selected candidate biomarkers from the quantitative-SWATH analysis were validated in EVs from independent morbid obese and from moderate obese to lean individuals showing that morbid obese VAT vesicles are characterized by a diminution of syntenin 1 and the elevation of TGFBI and mimecan. Interestingly, TGFBI and mimecan containing vesicles could be detected and quantified at circulating level in plasma. Thus, a significant elevation of -TGFBI-EVs was detected on those obese patients with a history of T2D compared to nondiabetic, and an augmentation of mimecan-EVs in obese plasma compared to those in healthy lean individuals. Thus, we conclude that obese AT release functional EVs carrying AT and obesity candidate biomarkers which vary regarding the AT of origin. Our findings suggest that circulating EV-TGFBI may facilitate monitoring T2D status in obese patients, and EV-mimecan may be useful to track adiposity, and more precisely, visceral obesity.
Assuntos
Tecido Adiposo Branco/metabolismo , Vesículas Extracelulares/metabolismo , Obesidade/patologia , Proteínas/metabolismo , Tecido Adiposo Branco/patologia , Adulto , Biomarcadores/sangue , Biomarcadores/metabolismo , Diabetes Mellitus Tipo 2/sangue , Proteínas da Matriz Extracelular/metabolismo , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologia , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade Mórbida/metabolismo , Obesidade Mórbida/patologia , Proteínas/análise , Gordura Subcutânea/metabolismo , Gordura Subcutânea/patologia , Sinteninas/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
Objective: We aimed to investigate insulin-, mTOR- and SGK1-dependent signaling basal states in morbidly obese patients' fat. We analyzed the correlation between the signaling activity, carbohydrate metabolism, and incretin profiles of patients. Methods: The omental and subcutaneous fat was obtained in patients with obesity. The omental study included 16 patients with normal glucose tolerance (NGT) and 17 patients with type 2 diabetes mellitus (T2DM); the subcutaneous study included 9 NGT patients and 12 T2DM patients. Insulin resistance was evaluated using the hyperinsulinemic euglycemic clamp test and HOMA-IR index. The oral glucose tolerance test (OGTT) for NGT patients and mixed meal tolerance test (MMTT) for T2DM patients were performed. The levels of incretins (GLP-1, GIP, oxyntomodulin) and glucagon were measured during the tests. Signaling was analyzed by Western blotting in adipose tissue biopsies. Results: We have shown equal levels of basal phosphorylation of insulin- and mTOR-dependent signaling in omental fat depot in NGT and T2DM obese patients. Nevertheless, pNDRG1-T346 was decreased in omental fat of T2DM patients. Correlation analysis has shown an inverse correlation of pNDRG1-T346 in omental fat and diabetic phenotype (HbA1c, impaired incretin profile (AUC GLP-1, glucagon)). Moreover, pNDRG1-T346 in subcutaneous fat correlated with impaired incretin levels among obese patients (inverse correlation with AUC glucagon and AUC GIP). Conclusions: According to results of the present study, we hypothesize that phosphorylation of pNDRG1-T346 can be related to impairment in incretin hormone processing. pNDRG1-T346 in adipose tissue may serve as a marker of diabetes-associated impairments of the systemic incretin profile and insulin sensitivity.
Assuntos
Tecido Adiposo/metabolismo , Proteínas de Ciclo Celular/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Incretinas/sangue , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Obesidade Mórbida/metabolismo , Tecido Adiposo/patologia , Adulto , Biomarcadores/metabolismo , Biópsia , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Feminino , Teste de Tolerância a Glucose , Humanos , Incretinas/metabolismo , Resistência à Insulina/fisiologia , Masculino , Metaboloma , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Obesidade Mórbida/patologia , FosforilaçãoRESUMO
Bariatric surgery (BS) is an effective treatment for morbid obesity. However, a simple and easy-to-use tool for the prediction of BS unsuccess is still lacking. Baseline and follow-up data from 300 consecutive patients who underwent BS were retrospectively collected. Supervised regression and machine-learning techniques were used for model development, in which BS unsuccess at 2 years was defined as a percentage of excess-weight-loss (%EWL) < 50%. Model performances were also assessed considering the percentage of total-weight-loss (%TWL) as the reference parameter. Two scoring systems (NAG-score and ENAG-score) were developed. NAG-score, comprising only pre-surgical data, was structured on a 4.5-point-scale (2 points for neck circumference ≥ 44 cm, 1.5 for age ≥ 50 years, and 1 for fasting glucose ≥ 118 mg/dL). ENAG-score, including also early post-operative data, was structured on a 7-point-scale (3 points for %EWL at 6 months ≤ 45%, 1.5 for neck circumference ≥ 44 cm, 1 for age ≥ 50 years, and 1.5 for fasting glucose ≥ 118 mg/dL). A 3-class-clustering was proposed for clinical application. In conclusion, our study proposed two scoring systems for pre-surgical and early post-surgical prediction of 2-year BS weight-loss, which may be useful to guide the pre-operative assessment, the appropriate balance of patients' expectations, and the post-operative care.
Assuntos
Cirurgia Bariátrica , Obesidade Mórbida , Resultado do Tratamento , Redução de Peso , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Obesidade Mórbida/patologia , Obesidade Mórbida/cirurgia , Estudos RetrospectivosRESUMO
Development and severity of nonalcoholic fatty liver disease (NAFLD) have been linked to obesity and white adipose tissue (WAT) dysfunction plays a key role in this relation. We compared the main features of subcutaneous (SAT) and visceral WAT (VAT) tissue dysfunction in 48 obese women without (Ob) and with NAFLD (Ob-NAFLD) undergoing bariatric surgery and matched for age, BMI and T2D status. Fat cell area, adipocyte size distribution, the degree of histological fibrosis and the mRNA expression of adipokines and genes implicated in inflammation, adipogenesis, angiogenesis, metabolism and extracellular matrix remodeling were measured by RT-qPCR in both fat depots. Ob-NAFLD group showed higher TG and lower HDL circulating levels, increased VAT fat cell area and similar WAT fibrosis in comparison with Ob group. A sPLS-DA was performed in order to identify the set of genes that better characterize the presence of NAFLD. Finally, we build a multinomial logistic model including seven genes that explained 100% of the variance in NAFLD and correctly predicted 100% of cases. Our data support the existence of distinctive NAFLD signatures in WAT from women with severe obesity. A better understanding of these pathways may help in future strategies for the prevention and treatment of NAFLD.
Assuntos
Adipocinas/biossíntese , Regulação da Expressão Gênica , Gordura Intra-Abdominal/metabolismo , Modelos Biológicos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade Mórbida/metabolismo , Gordura Subcutânea/metabolismo , Adulto , Feminino , Humanos , Gordura Intra-Abdominal/patologia , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade Mórbida/patologia , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Gordura Subcutânea/patologiaRESUMO
Background: Obesity is a multifactorial disease, which is strongly associated to other metabolic disorders. Bariatric surgery is the most effective treatment of morbid obesity. The role of beta cell function in weight loss after bariatric surgery is uncertain. Aim: To evaluate the association between beta cell function and percentage of total body weight loss (TBWL%) 1, 2, 3, and 4 years after bariatric surgery in patients with morbid obesity. Methods: Retrospective longitudinal study in patients with morbid obesity followed in our center between January 2010 and July 2018. Patients were excluded if they had diabetes at baseline or missing data on the needed parameters. We evaluated baseline Homeostatic Model Assessment of IR, Homeostatic Model Assessment of ß-cell function (HOMA-beta), Quantitative Insulin Sensitivity Check Index, and Matsuda and DeFronzo index, and TBWL% at years 1 to 4. Linear regression models were used to evaluate the association of indexes of insulin resistance with TBWL% (unadjusted and adjusted for age, sex, BMI, and type of surgery). Results: There were 1,561 patients included in this analysis. HOMA-beta was negatively associated with TBWL% at second, third, and fourth years post-surgery (ß = -1.04 [-1.82 to -0.26], p<0.01; ß = -1.16 [-2.13 to -0.19], p=0.02; ß = -1.29 [-2.64 to 0.06], p=0.061, respectively). This was not observed in the first year post-surgery nor for the other indexes. Glycemia at baseline was positively associated to EWL% at second and third years post-surgery. Conclusion: ß-cell function at baseline seems to be associated to long-term weight loss, explicitly after the first year post bariatric surgery. This might be a helpful predictor of weight loss in clinical practice.
Assuntos
Cirurgia Bariátrica/métodos , Índice de Massa Corporal , Resistência à Insulina , Células Secretoras de Insulina/fisiologia , Obesidade Mórbida/cirurgia , Redução de Peso , Adulto , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Obesidade Mórbida/patologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Obesity is a metabolic chronic disease with important associated morbidities and mortality. Bariatric surgery is the most effective treatment for maintaining long-term weight loss in severe obesity and, consequently, for decreasing obesity-related complications, including chronic inflammation. AIM: To explore changes in components of the inflammasome machinery after bariatric surgery and their relation with clinical/biochemical parameters at baseline and 6 months after bariatric surgery. PATIENTS AND METHODS: Twenty-two patients with morbid-obesity that underwent bariatric surgery (sleeve gastrectomy and Roux-en-Y gastric bypass) were included. Epidemiological/clinical/anthropometric/biochemical evaluation was performed at baseline and 6 months after bariatric surgery. Inflammasome components and inflammatory-associated factors [nucleotide-binding oligomerization domain-like receptors (NLRs), inflammasome activation components, cytokines and inflammation/apoptosis-related components, and cell-cycle and DNA-damage regulators) were evaluated in peripheral blood mononuclear cells (PBMCs) at baseline and 6 months after bariatric surgery. Clinical molecular correlations/associations were analyzed. Functional parameters (lipid accumulation/viability/apoptosis) were analyzed in response to specific inflammasome components silencing in liver HepG2 cells). RESULTS: A profound dysregulation of inflammasome components after bariatric surgery was found, especially in NLRs and cell-cycle and DNA damage regulators. Several components were associated with baseline metabolic comorbidities including type 2 diabetes (C-C motif chemokine ligand 2/C-X-C motif chemokine receptor 1/sirtuin 1), hypertension (absent in melanoma 2/ASC/purinergic receptor P2X 7), and dyslipidemia [C-X-C motif chemokine ligand 3 (CXCL3)/NLR family pyrin domain containing (NLRP) 7) and displayed changes in their molecular profile 6 months after bariatric surgery. The gene expression fingerprint of certain factors NLR family CARD domain containing 4 (NLRC4)/NLRP12/CXCL3)/C-C motif chemokine ligand 8/toll-like receptor 4) accurately differentiated pre- and postoperative PBMCs. Most changes were independent of the performed surgical technique. Silencing of NLRC4/NLRP12 resulted in altered lipid accumulation, apoptosis rate, and cell viability in HepG2 cells. CONCLUSION: Bariatric surgery induces a profound alteration in the gene expression pattern of components of the inflammasome machinery in PBMCs. Expression and changes of certain inflammasome components are associated to baseline metabolic comorbidities, including type 2 diabetes, and may be related to the improvement and reversion of some obesity-related comorbidities after bariatric surgery.
Assuntos
Cirurgia Bariátrica/efeitos adversos , Diabetes Mellitus Tipo 2/patologia , Dislipidemias/patologia , Mediadores da Inflamação/metabolismo , Inflamação/patologia , Leucócitos Mononucleares/patologia , Obesidade Mórbida/cirurgia , Adulto , Biomarcadores/metabolismo , Doença Crônica , Estudos de Coortes , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Dislipidemias/etiologia , Dislipidemias/metabolismo , Feminino , Seguimentos , Gastrectomia/efeitos adversos , Humanos , Inflamassomos/metabolismo , Inflamação/etiologia , Inflamação/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/patologia , PrognósticoRESUMO
Growth differentiating factor 15 (GDF15) is expressed in the intestine and is one of the most recently identified satiety peptides. The mechanisms controlling its secretion are unclear. The present study investigated whether plasma GDF15 concentrations are meal-related and if potential responses depend on macronutrient type or are affected by previous bariatric surgery. The study included 1) volunteers ingesting rapidly vs. slowly digested carbohydrates (sucrose vs. isomaltose; n = 10), 2) volunteers who had undergone Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery and unoperated matched controls ingesting a liquid mixed meal (n = 9-10 in each group), and 3) individuals with previous RYGB compared with unoperated controls ingesting isocaloric glucose, fat, or protein (n = 6 in each group). Plasma was collected after an overnight fast and up to 6 h after ingestion (≥12 time points). In cohort 1, fasting GDF15 concentrations were â¼480 pg/mL. Concentrations after sucrose or isomaltose intake did not differ from baseline (P = 0.26 to P > 0.99) and total area under the curves (tAUCs were similar between groups (P = 0.77). In cohort 2, fasting GDF15 concentrations were as follows (pg/mL): RYGB = 540 ± 41.4, SG = 477 ± 36.4, and controls = 590 ± 41.8, with no between-group differences (P = 0.73). Concentrations did not increase at any postprandial time point (over all time factor: P = 0.10) and tAUCs were similar between groups (P = 0.73). In cohort 3, fasting plasma GDF15 was similar among the groups (P > 0.99) and neither glucose, fat, nor protein intake consistently increased the concentrations. In conclusion, we find that plasma GDF15 was not stimulated by meal intake and that fasting concentrations did not differ between RYGB-, SG-, and body mass index (BMI)-matched controls when investigated during the weight stable phase after RYGB and SG.NEW & NOTEWORTHY Our combined data show that GDF15 does not increase in response to a liquid meal. Moreover, we show for the first time that ingestion of sucrose, isomaltose, glucose, fat, or protein also does not increase plasma GDF15 concentrations, questioning the role of GDF15 in regulation of food source preference. Finally, we find that neither fasting nor postprandial plasma GDF15 concentrations are increased in individuals with previous bariatric surgery compared with unoperated body mass index (BMI)-matched controls.
Assuntos
Cirurgia Bariátrica/métodos , Biomarcadores/sangue , Trato Gastrointestinal/metabolismo , Fator 15 de Diferenciação de Crescimento/sangue , Refeições , Obesidade Mórbida/sangue , Adulto , Glicemia/análise , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos Cross-Over , Feminino , Seguimentos , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/patologia , Obesidade Mórbida/cirurgia , Período Pós-Prandial , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Redução de PesoRESUMO
Nonalcoholic steatohepatitis (NASH) and glucose intolerance are associated with an increased risk of mortality in patients with severe obesity; however, whether histological findings of the liver are related to glucose intolerance in these patients remain unknown. Sixty-nine consecutive patients who underwent metabolic surgery between June 2008 and February 2020 were included; histological findings of the liver and laboratory data were analyzed. Twenty patients with biopsy-proven NASH were chronologically evaluated using sequential biopsies; data before metabolic surgery was considered as the baseline. Glucose intolerance-demonstrated by an increased area under the curve (AUC) for blood sugar (BS) during the 75-g oral glucose tolerance test-and increased homeostatic model assessment for insulin resistance (HOMA-IR) correlated with the grade of hepatocyte ballooning in patients. Patients with persistent ballooning at the follow-up biopsy had a higher HOMA-IR, high AUC for BS, and lower adiponectin level than those in patients in whom ballooning was eliminated, while there was no significant difference in body weight. We concluded that glucose intolerance was associated with the grade of hepatocyte ballooning; additionally, persistent hepatocyte ballooning sustained glucose intolerance, while elimination of hepatocyte ballooning improved the condition. Glucose intolerance may, thus, mediate balloon formation of the hepatocyte.