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Sleeve gastrectomy (SG) is the most widely used bariatric procedures globally, which could improve glucose and lipid metabolism dramatically. Circular RNAs (circRNAs) are being increasingly implicated in numerous pathophysiological processes. However, for diabetes mellitus (DM), the expression and function of circRNAs remain largely undetermined, in particular, whether circRNAs mediate the amelioration of DM observed after SG. Using a diabetic rat model, we subjected liver tissue from SG and sham-operated rats to RNA sequencing. Amongst the 103 differentially regulated circRNAs identified in diabetic rats after SG, we focused on circDOCK7, a highly expressed circRNA derived from the back-splicing of the DOCK7 gene. Silencing of circDOCK7 significantly inhibited cellular proliferation and induction of apoptosis in insulin-resistant rat hepatocytes. Further analysis indicated circDOCK7 harbored binding sites for miR-139-3p and regulated the expression of minichromosome maintenance 3 (MCM3) through sequestration of miR-139-3p. Our findings therefore demonstrate a novel regulatory pathway involving circDOCK7 that regulates cellular proliferation and apoptosis through increasing the expression of MCM3. Overall, our study establishes a list of specific circRNAs expressed in diabetic rat liver after SG including circDOCK7 which serve as potential biomarkers and treatment targets for DM patients.
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Apoptosis/genética , Diabetes Mellitus Experimental/genética , Regulación hacia Abajo/genética , Gastrectomía , Hepatocitos/patología , MicroARNs/metabolismo , Componente 3 del Complejo de Mantenimiento de Minicromosoma/metabolismo , ARN Circular/metabolismo , Animales , Secuencia de Bases , Peso Corporal , Línea Celular , Proliferación Celular/genética , Diabetes Mellitus Experimental/patología , Conducta Alimentaria , Silenciador del Gen , Glucosa/metabolismo , Hepatocitos/metabolismo , Homeostasis , Masculino , MicroARNs/genética , Componente 3 del Complejo de Mantenimiento de Minicromosoma/genética , Estabilidad del ARN/genética , ARN Circular/genética , Ratas WistarRESUMEN
BACKGROUND: Pancreatic neuroendocrine tumors (pNETs) uncommonly present as cystic lesions. There is a gap in knowledge of their clinicopathological characteristics and biological behaviors. Previous reported studies remained inconsistent and controversial. The purpose of this study is to investigate the clinicopathological features of cystic pNET and determine if it represents a distinct clinical entity by comparing its characteristics with those of solid pNETs. METHODS: Patients with pNETs who underwent surgical resections from January 2014 to April 2019 at Qilu Hospital of Shandong University were reviewed retrospectively. Demographics, clinical characteristics, surgical data, and oncological as well as histological characteristics of cystic pNETs and their solid counterparts were collected and analyzed. RESULTS: A total of 122 patients were included in this study, and 10.7% (13/122) patients were cystic. There is no significant difference between cystic pNETs and solid pNETs in age (43.6 ± 15.8 versus 50.9 ± 14.5 y, P = 0.093) and sex distribution (P = 0.085). Cystic pNETs are more likely to be asymptomatic (61.5% versus 23.9%, P = 0.008) and nonfunctional (92.3% versus 52.7%, P = 0.006) than solid pNETs. However, the tumor size (4.8 ± 4.5 versus 2.8 ± 1.9 cm, P = 0.124), proportion of multiple endocrine neoplasia type 1 (92.3% versus 98.2%, P = 0.289), and tumor location (P = 0.154) are similar in both groups. Compared with solid pNETs, cystic pNETs have a lower Ki-67 index and incidence of liver metastasis, but the difference is not significant. CONCLUSIONS: Cystic pNETs are more likely to be nonfunctional and indolent and seem to exhibit less aggressive biological behaviors than solid pNETs. Conservative approach should be considered for certain selected patients.
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Tumores Neuroendocrinos/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adulto , Anciano , Tratamiento Conservador , Femenino , Humanos , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Tumores Neuroendocrinos/metabolismo , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/cirugía , Pancreatectomía , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Bariatric surgeries have been shown to be effective in reversing damaged pulmonary function in individuals suffering from obesity and type 2 diabetes mellitus, whereas its underlying mechanisms remain largely unknown. METHODS: Sleeve gastrectomy (SG) was performed on obese and diabetic Wistar rats, and their pulmonary function and lung tissues were compared to sham-operated (SH) obese and diabetic rats, and age-matched healthy controls (C) to explore the improvements in microstructures and expression of surfactant protein (SP)-A and -C at postoperative 4th, 8th, and 12th week. RESULT: Apart from the profound metabolic changes and improvement in pulmonary function, lung volume was restored along with an improved diffusion capacity noted by thinned capillary basement membrane and decreased harmonic mean length of diffusion barrier in SG rats. The digital slices of light microscope showed the general changes brought on by the SG, including normalized basic structures, ameliorated inflammatory status, as well as reduced lipid deposition, where the hydroxyproline (HYP), triglyceride (TG) assays, and electron microscope further suggested that the improvement in alveolar structures lies in reduced collagen fibers, lipids and septal tissues, increased capillary blood, and normalized alveolar type 2 (AT2) cells. Besides, disrupted SP-A and SP-C expression were also normalized after SG. CONCLUSION: The improvement of lung function after SG is related to the ameliorated alveolar structures, and surface protein expression induced by weight loss and improved glucose metabolism.
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Diabetes Mellitus Experimental/cirugía , Gastrectomía , Obesidad/cirugía , Alveolos Pulmonares/anatomía & histología , Surfactantes Pulmonares/química , Animales , Pulmón , Alveolos Pulmonares/patología , Alveolos Pulmonares/ultraestructura , Ratas , Ratas Wistar , Pérdida de PesoRESUMEN
Bariatric surgery has been reported to relieve diabetic cardiomyopathy (DCM) effectively. However, the mechanisms remain largely unknown. To determine the effects of bariatric surgery on DCM via modulation of myocardial Ca2+ homeostasis and autophagy, sleeve gastrectomy (SG), duodenal-jejunal bypass (DJB), and sham surgeries were performed in diabetic rats induced by high-fat diet and a low dose of streptozotocin. Cardiac remodeling was assessed by a series of morphometric and histological analyses. Transthoracic echocardiography and hemodynamic measurements were performed to determine cardiac function. Ca2+ homeostasis was evaluated by measuring Ca2+ transients with fura-2 AM in isolated ventricular myocytes along with detection of the abundance of Ca2+ regulatory proteins in the myocardium. Myocardial autophagic flux was determined by expression of autophagy-related proteins in the absence and presence of chloroquine. Both SG and DJB surgery alleviated DCM morphologically and functionally. Ca2+ transients exhibited a significantly higher amplitude and faster decay after SG and DJB, which could be partially explained by increased expression of ryanodine receptor 2, sarco(endo)plasmic reticulum Ca2+-2ATPase, 12.6-kDa FK506-binding protein, and hyperphosphorylation of phospholamban. In addition, a lower level of light chain 3B and higher level of p62 were detected after both SG and DJB, which was not reversed by chloroquine treatment and associated with activated mammalian target of rapamycin and attenuated AMP-activated protein kinase signaling pathway. Collectively, these results provided evidence that bariatric surgery could alleviate DCM effectively, which may result, at least in part, from facilitated Ca2+ homeostasis and attenuated autophagy, suggesting a potential choice for treatment of DCM when properly implemented. NEW & NOTEWORTHY The present study is the first to investigate the modulation of myocardial Ca2+ homeostasis and autophagy after bariatric surgery and to examine its effects on diabetic cardiomyopathy. Bariatric surgery could facilitate myocardial Ca2+ homeostasis and attenuate myocardial autophagy, contributing to the alleviation of cardiomyopathy morphologically and functionally in a diabetic rat model.
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Autofagia , Señalización del Calcio , Cardiomiopatías Diabéticas/prevención & control , Gastrectomía , Derivación Gástrica , Miocardio/metabolismo , Obesidad/cirugía , Animales , Glucemia/metabolismo , Células Cultivadas , Diabetes Mellitus Experimental/inducido químicamente , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/patología , Dieta Alta en Grasa , Lípidos/sangre , Masculino , Miocardio/patología , Obesidad/sangre , Obesidad/complicaciones , Ratas Sprague-Dawley , Estreptozocina , Función Ventricular Izquierda , Remodelación Ventricular , Pérdida de PesoRESUMEN
Pancreatic cancer (PC) is one of the most lethal malignancies. Recent studies indicate that patients with incidentally diagnosed PC have better prognosis than those with symptoms and that there is a sufficient window for early detection. However, effective early diagnosis remains difficult and depends mainly on imaging modalities and the development of screening methodologies with highly sensitive and specific biomarkers. This review summarizes recent advances in effective screening for early diagnosis of PC using imaging modalities and novel molecular biomarkers discovered from various "omics" studies including genomics, epigenomics, non-coding RNA, metabonomics, liquid biopsy (CTC, ctDNA and exosomes) and microbiomes, and their use in body fluids (feces, urine and saliva). Although many biomarkers for early detection of PC have been discovered through various methods, larger scale and rigorous validation is required before their application in the clinic. In addition, more effective and specific biomarkers of PC are urgently needed.
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Detección Precoz del Cáncer/métodos , Neoplasias Pancreáticas/diagnóstico , Diagnóstico por Imagen , Predisposición Genética a la Enfermedad , Genómica/métodos , Humanos , Microbiota , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/microbiología , Pronóstico , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Differences in the preoperative characteristics and weight loss outcomes after sleeve gastrectomy (SG) between patients with familial aggregation of obesity (FAO) and patients with sporadic obesity (SO) have not been elucidated. AIM: To explore the impact of SG on weight loss and the alleviation of obesity-related comorbidities in individuals with FAO. METHODS: A total of 193 patients with obesity who underwent SG were selected. Patients with FAO/SO were matched 1:1 by propensity score matching and were categorized into 4 groups based on the number of first-degree relatives with obesity (1SO vs 1FAO, 2SO vs 2FAO). The baseline characteristics, weight loss outcomes, prevalence of obesity-related comorbidities and incidence of major surgery-related complications were compared between groups. RESULTS: We defined FAO as the presence of two or more first-degree relatives with obesity. Patients with FAO did not initially show significant differences in baseline data, short-term postoperative weight loss, or obesity-related comorbidities when compared to patients with SO preoperatively. However, distinctions between the two groups became evident at the two-year mark, with statistically significant differences in both percentage of total weight loss (P = 0.006) and percentage of excess weight loss (P < 0.001). The FAO group exhibited weaker remission of type 2 diabetes mellitus (T2DM) (P = 0.031), hyperlipidemia (P = 0.012), and non-alcoholic fatty liver disease (NAFLD) (P = 0.003) as well as a lower incidence of acid reflux (P = 0.038). CONCLUSION: FAO patients is associated with decreased mid-to-long-term weight loss outcomes; the alleviation of T2DM, hyperlipidemia and NAFLD; and decreased incidence of acid reflux postoperatively.
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Gastrectomía , Pérdida de Peso , Humanos , Masculino , Femenino , Gastrectomía/efectos adversos , Gastrectomía/métodos , Adulto , Resultado del Tratamiento , Persona de Mediana Edad , Estudios Retrospectivos , Diabetes Mellitus Tipo 2/cirugía , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Comorbilidad , Obesidad/cirugía , Obesidad/diagnóstico , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad Mórbida/cirugía , Obesidad Mórbida/complicaciones , Cirugía Bariátrica/métodos , Puntaje de Propensión , Enfermedad del Hígado Graso no Alcohólico/cirugía , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , IncidenciaRESUMEN
Background: The obesity epidemic has been on the rise due to changes in living standards and lifestyles. To combat this issue, sleeve gastrectomy (SG) has emerged as a prominent bariatric surgery technique, offering substantial weight reduction. Nevertheless, the mechanisms that underlie SG-related bodyweight loss are not fully understood. Methods: In this study, we conducted a collection of preoperative and 3-month postoperative serum and fecal samples from patients who underwent laparoscopic SG at the First Affiliated Hospital of Shandong First Medical University (Jinan, China). Here, we took an unbiased approach of multi-omics to investigate the role of SG-altered gut microbiota in anti-obesity of these patients. Non-target metabolome sequencing was performed using the fecal and serum samples. Results: Our data show that SG markedly increased microbiota diversity and Rikenellaceae, Alistipes, Parabacteroides, Bactreoidales, and Enterobacteraies robustly increased. These compositional changes were positively correlated with lipid metabolites, including sphingolipids, glycerophospholipids, and unsaturated fatty acids. Increases of Rikenellaceae, Alistipes, and Parabacteroide were reversely correlated with body mass index (BMI). Conclusion: In conclusion, our findings provide evidence that SG induces significant alterations in the abundances of Rikenellaceae, Alistipes, Parabacteroides, and Bacteroidales, as well as changes in lipid metabolism-related metabolites. Importantly, these changes were found to be closely linked to the alleviation of obesity. On the basis of these findings, we have identified a number of microbiotas that could be potential targets for treatment of obesity.
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Cirugía Bariátrica , Microbioma Gastrointestinal , Humanos , Metabolismo de los Lípidos , Obesidad/cirugía , Cirugía Bariátrica/métodos , Gastrectomía/métodosRESUMEN
Objective: This study aimed to investigate the feasibility, efficacy, and safety of laparoscopic transabdominal preperitoneal (TAPP) repair in the treatment of inguinal hernia in patients on peritoneal dialysis, and the optimal timing for initiating postoperative peritoneal dialysis. Methods: We conducted a retrospective analysis of the clinical data pertaining to patients on peritoneal dialysis with inguinal hernias treated with TAPP repair in the First Affiliated Hospital of Shandong First Medical University from July 15, 2020 to December 15, 2022. Follow-up observations of the treatment effect were also analyzed. Results: A total of 15 patients underwent TAPP repair with success. Contralateral occult hernias were found in 3 cases intraoperatively and were treated simultaneously. During the operation, it was found that the peritoneal dialysis tube was completely wrapped in the omentum majus in 1 case and incompletely wrapped in 5 cases and was separated smoothly under laparoscopy. Conclusion: For patients on peritoneal dialysis with inguinal hernia, TAPP repair has the advantages of less trauma, simultaneous treatment of contralateral occult hernias, adjustment and fixation of peritoneal dialysis tubes, lower incision complication rates, and lower recurrence rates, compared with open surgery. With the gradual resumption of peritoneal dialysis 7 days postoperatively, TAPP repair can be performed safely and effectively in this population group; thus it is a procedure worth promoting.
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Hernia Inguinal , Laparoscopía , Diálisis Peritoneal , Humanos , Hernia Inguinal/cirugía , Hernia Inguinal/etiología , Estudios Retrospectivos , Herniorrafia/métodos , Laparoscopía/métodos , Mallas Quirúrgicas , Resultado del Tratamiento , RecurrenciaRESUMEN
BACKGROUND: Conventional laparoscopic sleeve gastrectomy (CLSG) has been conducted in multiple centers for treating morbid obesity, however, there are no standard criteria for (1) placing the trocar; and (2) how many trocars should be used. Single-incision laparoscopic sleeve gastrectomy (SLSG), a newly emerged technique in 2008, has been proposed as an alternative to CLSG in recent years, however, there is no definite evidence for this. MATERIALS AND METHODS: A systematic literature search was performed using the PubMed, Embase, Web of Science, and Cochrane Library databases for laparoscopic sleeve gastrectomy cases from January 2006 to October 2022. We then summarized the trocar numbers and placement patterns among these studies. A meta-analysis was conducted to compare the difference between SLSG and CLSG in the perioperative and postoperative indices. RESULTS: A total of 61 studies involving 20 180 patients who underwent laparoscopic sleeve gastrectomy for treating morbid obesity were included in the systematic review, including 11 on SLSG, 35 on CLSG, and 15 studies comparing SLSG and CLSG. A systematic review showed that the trocar number varied in different CLSG studies, mainly using four or five trocars. The trocars were mainly placed in position, presenting an inverted trapezoid pattern and a left-predominant pattern. Meta-analysis showed that the operative time in the SLSG was significantly higher than that in the CLSG, and the pain Visual Analog Scale rating on postoperative day 1 in the CLSG was significantly higher than in the SLSG. There were no statistical significances in the other complications or surgical efficiency. CONCLUSIONS: In the CLSG, the majority of the trocars were arranged in an inverted trapezoid pattern and were of the left-predominant type. Although SLSG is a feasible technique in selected patients, there is insufficient evidence to recommend its widespread use compared with CLSG. High-quality randomized controlled trials with large study populations and long follow-up periods will be required in the future.
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Cirugía Bariátrica , Laparoscopía , Obesidad Mórbida , Humanos , Obesidad Mórbida/cirugía , Laparoscopía/métodos , Cirugía Bariátrica/efectos adversos , Cirugía Bariátrica/métodos , Instrumentos Quirúrgicos , Gastrectomía/métodosRESUMEN
Purpose: This study aimed to investigate the surgical treatment strategy of recurrent parastomal hernia (PH) and show its safety, feasibility, and outcomes at a mid-term follow-up. Methods: A total of 17 cases of recurrent PH treated at our hospital between January 2016 and October 2021 were included in this retrospective analysis. Patient characteristics were recorded, and the classification of PH, operative time, intraoperative blood loss, hernia repair techniques, follow-up times, complications, as well as recurrence were compared and analyzed. Results: Altogether, 17 patients with recurrent PH underwent successful hernia repair via surgical treatment at The First Affiliated Hospital of Shandong First Medical University and Shandong University Qilu Hospital. No recurrence or severe complications were noted during follow-ups (mean 32.8 ± 3.77 [range 3-68] months). Conclusions: For recurrent PH, selecting a suitable repair approach based on intraperitoneal conditions such as infection, abdominal adhesions, or the length of the bowel loop, can help in achieving better therapeutic results. The lap-redo + Sugarbaker technique is worth recommending when the appropriate conditions are met.
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Introduction: Obesity is a metabolic disease accompanied by abnormalities in lipid metabolism that can cause hyperlipidemia, non-alcoholic fatty liver disease, and artery atherosclerosis. Sleeve gastrectomy (SG) is a type of bariatric surgery that can effectively treat obesity and improve lipid metabolism. However, its specific underlying mechanism remains elusive. Methods: We performed SG, and sham surgery on two groups of diet-induced obese mice. Histology and lipid analysis were used to evaluate operation effect. Immunohistochemistry, immunoblotting, real-time quantitative PCR, immunoprecipitation, immunofluorescence and mass spectrometry were used to reveal the potential mechanisms of SG. Results: Compared to the sham group, the SG group displayed a downregulation of deubiquitinase ubiquitin-specific peptidase 20 (USP20). Moreover, USP20 could promote lipid accumulation in vitro. Co-immunoprecipitation and mass spectrometry analyses showed that heat-shock protein family A member 2 (HSPA2) potentially acts as a substrate of USP20. HSPA2 was also downregulated in the SG group and could promote lipid accumulation in vitro. Further research showed that USP20 targeted and stabilized HSPA2 via the ubiquitin-proteasome pathway. Conclusion: The downregulation of the USP20-HSPA2 axis in diet-induced obese mice following SG improved lipid dysmetabolism, indicating that USP20-HSPA2 axis was a noninvasive therapeutic target to be investigated in the future.
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Dieta Alta en Grasa , Proteínas HSP70 de Choque Térmico , Obesidad , Ubiquitina Tiolesterasa , Animales , Ratones , Gastrectomía/métodos , Lípidos , Ratones Obesos , Obesidad/cirugía , Obesidad/complicacionesRESUMEN
Bioluminescence imaging is a non-invasive technology used to visualize physiological processes in animals and is useful for studying the dynamics of metabolic syndrome. Metabolic syndrome is a broad spectrum of diseases which are rapidly increasing in prevalence, and is closely associated with obesity, type 2 diabetes, nonalcoholic fatty liver disease, and circadian rhythm disorder. To better serve metabolic syndrome research, researchers have established a variety of animal models expressing luciferase, while also committing to finding more suitable luciferase promoters and developing more efficient luciferase-luciferin systems. In this review, we systematically summarize the applications of different models for bioluminescence imaging in the study of metabolic syndrome.
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Diabetic cardiomyopathy (DCM) is characterized by impaired diastolic and systolic myocardial performance and is a major cause of morbidity and mortality in patients with diabetes. Surgical bariatric procedures, such as sleeve gastrectomy (SG), result in remission of type 2 diabetes (T2DM) and have benefits with myocardial function. Maintaining cardiac mitochondrial homeostasis is a promising therapeutic strategy for DCM. However, whether SG surgery affects mitochondrial function and its underlying mechanism remains unclear. This study aimed to investigate the effect of SG surgery on mitochondrial homeostasis and intracellular oxidative stress in rats with DCM. We also examined cellular phenotypes and molecular mechanisms in high glucose and high fat-stimulated myocytes. The rat model of DCM was established by high-fat diet feeding and low-dose streptozotocin injection. We observed a remarkably metabolic benefit of SG, including a reduced body weight, food intake, blood glucose levels, and restored glucose tolerance and insulin sensitivity post-operatively. Also, SG ameliorated the pathological cardiac hypertrophy, myocardial fibrosis and the dysfunction of myocardial contraction and diastole, consequently delayed the progression of DCM. Also, SG restored the mitochondrial dysfunction and fragmentation through the AMPK signaling activation mediated nuclear receptor subfamily 4 group A member 1 (NR4A1)/DRP1 suppression in vivo. H9c2 cardiomyocytes showed that activation of AMPK could reverse the mitochondrial dysfunction somehow. Collectively, our study provided evidence that SG surgery could alleviate mitochondrial dysfunction in DCM. Moreover, AMPK-activated NR4A1/DRP1 repression might act as a significant reason for maintaining mitochondrial homeostasis in the myocardium, thus contributing to morphological and functional alleviation of DCM.
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Diabetic cardiomyopathy (DCM) can develop in diabetes mellitus and is a major cause of morbidity and mortality. Surgical bariatric surgery procedures, such as sleeve gastrectomy (SG), result in remission of type 2 diabetes and have benefits regarding systolic and diastolic myocardial function. The NLR family pyrin domain containing 3 (NLRP3) inflammasome appears to participate in the development of DCM. However, whether SG surgery affects myocardial NLRP3 inflammasome-related pyroptosis to improve cardiac function remains unclear. This study was aimed at investigating the effect of SG surgery on NLRP3-associated pyroptosis in rats with DCM. We also examined cellular phenotypes and molecular mechanisms in high glucose-stimulated myocytes. The rat model of DCM was established by high-fat diet feeding and low-dose streptozotocin injection. We observed a metabolic benefit of SG, including a reduced body weight, food intake, and blood glucose levels and restored glucose tolerance and insulin sensitivity postoperatively. We observed a marked decline in glucose uptake in rats with DCM, and this was restored after SG. Also, SG alleviated the dysfunction of myocardial contraction and diastole, delayed the progression of DCM, and reduced the NLRP3 inflammasome-mediated myocardial pyroptosis in vivo. H9c2 cardiomyocytes showed membrane disruption and DNA damage under a high glucose stimulus, which suggested myocardial pyroptosis. Using a ROS scavenger or chloride channel blocker in vitro restored myocardial NLRP3-mediated pyroptosis. Furthermore, we found that chloride efflux acted downstream of ROS generation. In conclusion, SG may ameliorate or even reverse the progression of DCM. Our study provides evidence that the SG operation alleviates NLRP3 inflammasome dysregulation in DCM. Clearance of ROS overburden and suppression of chloride efflux due to SG might act as the proximal event before inhibition of NLRP3 inflammasome in the myocardium, thus contributing to morphological and functional alleviation of DCM.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Cardiomiopatías Diabéticas , Animales , Cloruros , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Cardiomiopatías Diabéticas/etiología , Gastrectomía , Glucosa/farmacología , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Sleeve gastrectomy (SG) can induce prominent remission of type 2 diabetes mellitus. However, the long-term remission rate of diabetes usually decreases over time. Oligofructose has been verified to modulate host metabolism. The aim of this study was to explore the protective effect of oligofructose on high-fat diet (HFD)-induced metabolic dysfunction after SG. AIM: To study the effect and mechanism of oligofructose on diabetic remission in diabetic rats after SG. METHODS: SG and SHAM operation were performed on diabetes rats induced with an HFD, nicotinamide, and low-dose streptozotocin. Then the rats in the SHAM and SG groups were continuously provided with the HFD, and the rats in sleeve gastrectomy-oligofructose group were provided with a specific HFD containing 10% oligofructose. Body weight, calorie intake, oral glucose tolerance test, homeostasis model assessment of insulin resistance, lipid profile, serum insulin, glucagon-like peptide 1 (GLP-1), total bile acids, lipopolysaccharide (LPS), and colonic microbiota levels were determined and compared at the designated time points. All statistical analyses were performed using Statistic Package for Social Science version 19.0 (IBM, United States), and the statistically significant difference was considered at P < 0.05. RESULTS: At 2 wk after surgery, rats that underwent SG exhibited improved indexes of glucose and lipid metabolism. Compared with the SG group, the rats from SG-oligofructose group exhibited better parameters of glucose and lipid metabolism, lower body weight (526.86 ± 21.51 vs 469.25 ± 21.84, P < 0.001), calorie intake (152.14 ± 9.48 vs 129.63 ± 8.99, P < 0.001), homeostasis model assessment of insulin resistance (4.32 ± 0.57 vs 3.46 ± 0.52, P < 0.05), and LPS levels (0.19 ± 0.01 vs 0.16 ± 0.01, P < 0.05), and higher levels of insulin (1.17 ± 0.17 vs 1.58 ± 0.16, P < 0.001) and GLP-1 (12.39 ± 1.67 vs 14.94 ± 1.86, P < 0.001), and relative abundances of Bifidobacterium (0.0034 ± 0.0014 vs 0.0343 ± 0.0064, P < 0.001), Lactobacillus (0.0161 ± 0.0037 vs 0.0357 ± 0.0047, P < 0.001), and Akkermansia muciniphila (0.0050 ± 0.0024 vs 0.0507 ± 0.0100, P < 0.001) at the end of the study. However, no difference in total bile acids levels was observed between the two groups. CONCLUSION: Oligofructose partially prevents HFD-induced glucose and lipid metabolism damage after SG, which may be due to the changes of calorie intake, insulin, GLP-1, LPS, and the gut microbiota in rats.
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PURPOSE: Oxidative stress and inflammation are important pathogenic mediators in diabetes-related organ damage. Accumulating evidence suggests that immunodeficiency in diabetes is associated with diabetes-induced spleen damage. Sleeve gastrectomy (SG) has been proved to improve diabetes and its multiple associated complications. However, the ameliorative role of SG against spleen damage in diabetes has not been investigated. MATERIALS AND METHODS: Animal model of diabetic obese rats induced by high-fat diet (HFD) combined with streptozotocin (STZ) was treated with sham operation, caloric restriction, and SG. Metabolic parameters were measured, and the morphological and histopathological changes, status of oxidative stress, and levels of inflammatory factors were evaluated. RESULTS: SG reduced body weight and improved glucose tolerance and insulin sensitivity in diabetic obese rats. SG significantly reversed splenic atrophy and alleviated abnormalities of white and red pulp. Additionally, SG also reversed the increased splenocyte apoptosis (P < 0.001). Meanwhile, indicators of oxidative stress including reactive oxygen species (ROS), nitric oxide (NO), malondialdehyde (MDA), and protein carbonylation were reduced, and the activity and expression of antioxidant enzymes including SOD and CAT were improved after SG. The mRNA expression of inflammatory factors in SG groups such as TNF-α (P < 0.001), IL-6 (P < 0.001), MCP-1 (P < 0.01), and ICAM-1 (P < 0.001) was also significantly reduced. CONCLUSION: SG ameliorates diabetes-related splenic injury by restoring the balance between oxidative stress process and antioxidant defense systems as well as reducing inflammation in the spleen. These findings indicate that SG is an appropriate therapeutic strategy for diabetes-related spleen damage.
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Diabetes Mellitus Experimental , Obesidad Mórbida , Animales , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/cirugía , Gastrectomía , Obesidad/cirugía , Obesidad Mórbida/cirugía , Estrés Oxidativo , Ratas , BazoRESUMEN
PURPOSE: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and sleeve gastrectomy (SG) is considered to be an effective strategy to improve pre-existing DN. However, the mechanism remains unknown. MATERIALS AND METHODS: Animal model of DN was induced by high-fat diet (HFD) and streptozotocin (STZ). SG or sham surgery was performed and rats were sacrificed at 4, 8, and 12 weeks after surgery. The basic parameters (blood glucose, body weight, kidney weight), indicators of renal function including serum creatinine (Scr), blood urea nitrogen (BUN), urine microalbumin, urine creatinine (Ucr), microalbumin creatinine ratio (UACR), ultrastructural changes of glomerulus, and the expression of nephrin gene and protein in glomerular podocytes were compared among groups. RESULTS: Blood glucose and body weight of SG rats were significantly lower than those of the sham-operated rats, and renal function of SG groups were also significantly improved within the postoperative period of 12 weeks. The results of periodic acid-Schiff staining (PAS) and transmission electron microscopy (TEM) showed that glomerular hypertrophy and accumulation of extracellular matrix proteins were significantly alleviated after SG, and the thickness of basement membrane and the fusion or effacement of foot processes were also significantly improved. The mRNA and protein expression of nephrin in SG groups was significantly higher than that in the sham group. CONCLUSION: These results suggest that SG attenuates DN by upregulating the expression of nephrin and improving the ultrastructure of glomerular filtration membrane. This study indicates that SG can be used as an available therapeutic intervention for DN.
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Diabetes Mellitus Experimental , Nefropatías Diabéticas , Obesidad Mórbida , Animales , Diabetes Mellitus Experimental/complicaciones , Gastrectomía , Proteínas de la Membrana , Obesidad Mórbida/cirugía , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Previous evidence has implied that obesity is an independent risk factor for developing cancer. Being closely related to obesity, type 2 diabetes mellitus provides a suitable environment for the formation and metastasis of tumors through multiple pathways. Although bariatric surgeries are effective in preventing and lowering the risk of various types of cancer, the underlying mechanisms of this effect are not clearly elucidated. AIM: To uncover the role and effect of sleeve gastrectomy (SG) in preventing lung cancer in obese and diabetic rats. METHODS: SG was performed on obese and diabetic Wistar rats, and the postoperative transcriptional and translational alterations of the endothelin-1 (ET-1) axis in the lungs were compared to sham-operated obese and diabetic rats and age-matched healthy controls to assess the improvements in endothelial function and risk of developing lung cancer at the postoperative 4th, 8th, and 12th weeks. The risk was also evaluated using nuclear phosphorylation of H2A histone family member X as a marker of DNA damage (double-strand break). RESULTS: Compared to obese and diabetic sham-operated rats, SG brought a significant reduction to body weight, food intake, and fasting blood glucose while improving oral glucose tolerance and insulin sensitivity. In addition, ameliorated levels of gene and protein expression in the ET-1 axis as well as reduced DNA damage indicated improved endothelial function and a lower risk of developing lung cancer after the surgery. CONCLUSION: Apart from eliminating metabolic disorders, SG improves endothelial function and plays a protective role in preventing lung cancer via normalized ET-1 axis and reduced DNA damage.
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Cirugía Bariátrica/métodos , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 2/cirugía , Endotelina-1/metabolismo , Neoplasias Pulmonares/prevención & control , Obesidad/cirugía , Animales , Glucemia/análisis , Glucemia/metabolismo , Roturas del ADN de Doble Cadena , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Dieta Alta en Grasa/efectos adversos , Endotelio/patología , Prueba de Tolerancia a la Glucosa , Histonas/metabolismo , Humanos , Pulmón/patología , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Obesidad/sangre , Obesidad/complicaciones , Obesidad/metabolismo , Fosfoproteínas/metabolismo , Fosforilación , Ratas , Estreptozocina/administración & dosificación , Estreptozocina/toxicidad , Pérdida de PesoRESUMEN
AIMS/INTRODUCTION: Duodenal-jejunal bypass (DJB) surgery has been reported to effectively relieve diabetic cardiomyopathy (DCM). However, the specific mechanisms remain largely unknown. The present study was designed to determine the alterations of myocardial glucose uptake (MGU) after DJB and their effects on DCM. MATERIALS AND METHODS: Duodenal-jejunal bypass and sham surgeries were carried out in diabetic rats induced by a high-fat diet and a low dose of streptozotocin, with chow-diet fed rats as controls. Bodyweight, food intake, glucose homeostasis and lipid profiles were measured at indicated time-points. Cardiac function was evaluated by transthoracic echocardiography and hemodynamic measurement. Cardiac remodeling was assessed by a series of morphometric analyses along with transmission electron microscopy. Positron-emission tomography with fluorine-18 labeled fluorodeoxyglucose was carried out to evaluate the MGU in vivo. Furthermore, myocardial glucose transporters (GLUT; GLUT1 and GLUT4), myocardial insulin signaling and GLUT-4 translocation-related proteins were investigated to elucidate the underlying mechanisms. RESULTS: The DJB group showed restored systolic and diastolic cardiac function, along with significant remission in cardiac hypertrophy, cardiac fibrosis, lipid deposit and ultrastructural disorder independent of weight loss compared with the sham group. Furthermore, the DJB group showed upregulated myocardial insulin signaling, hyperphosphorylation of AKT substrate of 160 kDa (AS160) and TBC1D1, along with preserved soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins, facilitating the GLUT-4 translocation to the myocardial cell surface and restoration of MGU. CONCLUSIONS: The present findings provide evidence that restoration of MGU is implicated in the alleviation of DCM after DJB through facilitating GLUT-4 translocation, suggesting a potential choice for treatment of human DCM if properly implemented.
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Cirugía Bariátrica/métodos , Diabetes Mellitus Experimental/complicaciones , Cardiomiopatías Diabéticas/prevención & control , Duodeno/cirugía , Transportador de Glucosa de Tipo 4/metabolismo , Glucosa/metabolismo , Yeyuno/cirugía , Miocardio/metabolismo , Animales , Diabetes Mellitus Experimental/fisiopatología , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/metabolismo , Masculino , Transporte de Proteínas , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Sleeve gastrectomy (SG) plus procedures have been developed to strengthen the effect of SG on diabetes control. The aim of this study was to compare diabetes control after SG plus bypass of the proximal small intestine with SG alone under adverse conditions for diabetes remission. METHODS: SG plus duodenojejunal bypass (SG-DJB), SG plus jejunojejunal bypass (SG-JJB), SG alone, and sham surgeries were performed in diabetic rats. A high-fat diet (HFD) was fed postoperatively to induce diabetes recurrence. Body weight, food intake, glucose tolerance, insulin sensitivity, serum hormones, hepatic function, and lipid profiles were measured postoperatively. RESULTS: SG-DJB, SG-JJB, and SG groups exhibited significant improvement in glucose tolerance and insulin sensitivity compared with the sham-operated group at 2 weeks postoperatively. Postoperative HFD induced obvious diabetes relapse and re-impaired insulin sensitivity at 16 weeks postoperatively. The SG-DJB and SG-JJB groups exhibited superior glucose tolerance and similar insulin sensitivity to SG alone at 16 weeks postoperatively. Compared with the SG alone, the SG-DJB and SG-JJB groups exhibited similar food intake, weight loss, fasting ghrelin, glucose-stimulated insulin secretion, and higher glucose-stimulated GLP-1 secretion. CONCLUSION: SG-DJB and SG-JJB provided better diabetes control than SG alone in rats fed a HFD postoperatively. Further clinical studies are expected to confirm the superiority of SG plus bypass of proximal small intestine.