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1.
Acta Pharm Sin B ; 14(8): 3576-3590, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39220873

RESUMO

Obesity is primarily caused by excessive intake as well as absorption of sugar and lipid. Postprandial surge in distention pressure and intestinal motility accelerates the absorption of nutrients. The response of intestinal epithelial cells to mechanical stimulation is not fully understood. Piezo1, a mechanosensitive ion channel, is widely expressed throughout the digestive tract. However, its function in intestinal nutrient absorption is not yet clear. In our study, excessive lipid deposition was observed in the duodenum of obese patients, while duodenal Piezo1-CaMKK2-AMPKα was decreased when compared to normal-weight individuals. Under high-fat diet condition, the Piezo1 iKO mice exhibited abnormally elevated sugar and lipid absorption as well as severe lipid deposition in the duodenum and liver. These phenotypes were mainly caused by the inhibition of duodenal CaMKK2-AMPKα and the upregulation of SGLT1 and DGAT2. In contrast, Yoda1, a Piezo1 agonist, was found to reduce intestinal lipid absorption in diet induced obese mice. Overexpression of Piezo1, stretch and Yoda1 inhibited lipid accumulation and the expression of DGAT2 and SGLT1, whereas knockdown of Piezo1 stimulated lipid accumulation and DGAT2 in Caco-2 cells. Our study reveals a previously unexplored mechanical regulation of nutrient absorption in intestinal epithelial cells, which may shed new light on the therapy of obesity.

2.
Obes Rev ; 25(11): e13812, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39191438

RESUMO

This study aimed to evaluate the efficacy and safety of duodenal-jejunal bypass liner (DJBL) for obesity and type 2 diabetes mellitus. A comprehensive search of electronic databases was conducted up to September 15, 2022. Thirty studies involving 1751 patients were included. At 12 months post-implantation, the reduction in body mass index (BMI) was 4.8 kg/m2 (95% CI 4.1, 5.5), with an excess weight loss of 41.3% (95% CI 33.4%,49.2%) and a total weight loss of 13.1% (95% CI 10.1%, 16.0%). Significant decrease was observed in HbA1c and fasting glucose, with a standardized mean difference of - 0.72 (95% CI - 0.95, - 0.48) and - 0.62 (95% CI - 0.82, - 0.42), respectively. However, these improvements in weight loss and glycemic control were only partially sustained after explantation. In situ, DJBL significantly improves blood pressure and lipid levels. The pooled early removal rate was 19%, and the incidence of severe adverse events was 17%, including device migration (6%), gastrointestinal hemorrhage (4%), device obstruction (4%), and hepatic abscess (2%). DJBL offers significant improvement in weight loss and glycemic control, as well as cardiovascular parameters while in situ. Further studies are warranted to better understand the long-term efficacy and safety of DJBL. The benefits of DJBL need to be carefully weighed against the risks in clinical decision-making.


Assuntos
Diabetes Mellitus Tipo 2 , Duodeno , Jejuno , Obesidade , Humanos , Diabetes Mellitus Tipo 2/cirurgia , Duodeno/cirurgia , Jejuno/cirurgia , Obesidade/cirurgia , Redução de Peso , Cirurgia Bariátrica/métodos , Cirurgia Bariátrica/efeitos adversos , Resultado do Tratamento , Glicemia/metabolismo
3.
Obes Surg ; 34(9): 3509-3512, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39042311

RESUMO

PURPOSE: Sleeve gastrectomy (SG) is the most performed metabolic and bariatric surgery (MBS). However, with the increase of SG in different regions, recurrent weight gain after SG is challenging for bariatric surgeons. We introduce a modified operation with a long, narrow pouch in RYGB (LN-RYGB) for weight regain after SG which enhanced the restrictive function in RYGB. METHODS AND RESULTS: The LN-RYGB has a longer and narrow gastric pouch for 10 cm. The length of small Roux and biliopancreatic are the same as RYGB. As a revisional surgery, the post-1 year excess weight loss percentage (%EWL) was 63.1% and total weight loss percentage (%TWL) was 29.1% in 5 cases. CONCLUSION: LN-RYGB is an optional treatment for recurrent weight gain after SG; a randomized control trial is needed to verify the long-term effect of LN-RYGB.


Assuntos
Gastrectomia , Derivação Gástrica , Obesidade Mórbida , Reoperação , Aumento de Peso , Humanos , Derivação Gástrica/métodos , Obesidade Mórbida/cirurgia , Gastrectomia/métodos , Feminino , Adulto , Masculino , Resultado do Tratamento , Redução de Peso , Pessoa de Meia-Idade , Recidiva
4.
Diabetol Metab Syndr ; 16(1): 163, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010180

RESUMO

BACKGROUND: Changes in microRNAs (miRNAs) are relevant to bariatric surgery and its comorbidities. The characteristics of changes in miRNAs of the early postoperative period following both bariatric procedures, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), as well as the factors that related to the effectiveness of early weight loss remain unclear. METHODS: We recruited 18 patients who performed SG and 15 patients who performed RYGB. Their preoperative and 1-month postoperative clinical data and fasting serum samples were collected, and the latter were analyzed by RNA-sequencing. Differential expression analysis of miRNAs was performed by the R-tool. Functional classification annotation and pathway enrichment analysis of targeted genes were analyzed by KOBAS software. The change profiles of miRNAs for both surgeries and their correlation with clinical characteristics and weight loss effectiveness were further analyzed. RESULTS: A total of 85 differentially expressed miRNAs were identified before and after SG, while a total of 76 were found before and after RYGB. The target genes of these miRNAs were similar in the Gene Ontology enrichment analysis in SG and RYGB, and the enrichment analysis in the Kyoto Encyclopedia of Genes and Genomes was mainly related to metabolic pathways. Hsa-miR-493-5p, hsa-miR-184, and hsa-miR-3199 exhibited similar changes in SG and RYGB, and the former two were correlated with clinical characteristics. Hsa-miR-6729-5p, hsa-miR-4659b-5p, and hsa-miR-2277-5p were correlated with the weight loss effectiveness of SG, while hsa-miR-4662a-5p was correlated with the weight loss effectiveness of RYGB. CONCLUSIONS: Short-term metabolic improvement and weight loss occurring after SG and RYGB surgery might be related to changes in miRNAs, which act on multiple biological pathways by regulating genes. In addition, some clinical characteristics and miRNAs were related to the effectiveness of early weight loss after SG and RYGB surgery. CLINICAL TRIAL REGISTRATION: ChiCTR2200058333.

5.
Small ; : e2402526, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958071

RESUMO

The intricate processes that govern the interactions between peripatetic immune cells and distal renal injury in obesity are not fully understood. Employing transcriptomic analysis of circulating extracellular vesicles (EVs), a marked amplification of small RNA (miR-3960) is discerned within CD3-CD19+ B cells. This RNA is found to be preferentially augmented in kidney tissues, contrasting with its subdued expression in other organs. By synthesizing dual-luciferase reporter assay with co-immunoprecipitation analysis, it is pinpointed that miR-3960 specifically targets the nuclear gene TRMT5, a pivotal actor in the methylation of mitochondrial tRNA. This liaison instigates aberrations in the post-transcriptional modifications of mitochondrial tRNA, engendering deficiencies within the electron respiratory chain, primarily attributable to the diminution of the mitochondrial bioenergetic compound (NDUFA7) complex I. Such perturbations lead to a compromised mitochondrial respiratory capacity in renal tubular cells, thereby exacerbating tubular injury. In contrast, EV blockade or miR-3960 depletion markedly alleviates renal tubular injury in obesity. This investigation unveils a hitherto unexplored pathway by which obesity-induced circulating immune cells remotely manipulate mitochondrial metabolism in target organs. The strategic targeting of obese EVs or infiltrative immune cells and their specifically secreted RNAs emerges as a promising therapeutic avenue to forestall obesity-related renal afflictions.

6.
Br J Pharmacol ; 181(19): 3743-3759, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38862812

RESUMO

BACKGROUND AND PURPOSE: Drug disposition undergoes significant alteration in patients with inflammatory bowel disease (IBD), yet circadian time-dependency of these changes remains largely unexplored. In this study, we aimed to determine the temporal effects of experimental colitis on drug disposition and toxicity. EXPERIMENTAL APPROACH: RNA-sequencing was used to screen genes relevant to colitis induced by dextran sodium sulfate in mice. Liver microsomes and pharmacokinetic analysis were used to analyze the activity of key enzymes. Dual luciferase assays and chromatin immunoprecipitation (ChIP) were employed to elucidate regulatory mechanisms. KEY RESULTS: RNA sequencing analysis revealed that colitis markedly influenced expression of cytochrome P450 (CYP) enzymes. Specifically, a substantial down-regulation of CYP1A2 and CYP2E1 was observed in livers of mice with colitis at Zeitgeber Time 8 (ZT8), with no significant changes detected at ZT20. At ZT8, the altered expression corresponded to diminished metabolism and enhanced incidence of hepato-cardiac toxicity of theophylline, a substrate specifically metabolized by these enzymes. A combination of assays, integrating liver-specific Bmal1 knockout and targeted activation of BMAL1 showed that dysregulation in CYP1A2 and CYP2E1 during colitis was attributable to perturbed BMAL1 functionality. Luciferase reporter and ChIP assays collectively substantiated the role of BMAL1 in regulating Cyp1a2 and Cyp2e1 transcription through its binding affinity to E-box-like sites. CONCLUSION AND IMPLICATION: Our findings establish a strong link between colitis and chronopharmacology, shedding light on how IBD affects drug disposition and toxicity over time. This research provides a theoretical foundation for optimizing drug dosage in patients with IBD.


Assuntos
Ritmo Circadiano , Colite , Camundongos Endogâmicos C57BL , Teofilina , Teofilina/farmacocinética , Animais , Colite/induzido quimicamente , Colite/metabolismo , Camundongos , Ritmo Circadiano/efeitos dos fármacos , Masculino , Sulfato de Dextrana , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP1A2/genética , Humanos , Microssomos Hepáticos/metabolismo
7.
Obes Surg ; 34(7): 2399-2410, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38862752

RESUMO

PURPOSE: There is a lack of evidence for treatment of some conditions including complication management, suboptimal initial weight loss, recurrent weight gain, or worsening of a significant obesity complication after one anastomosis gastric bypass (OAGB). This study was designed to respond to the existing lack of agreement and to provide a valuable resource for clinicians by employing an expert-modified Delphi consensus method. METHODS: Forty-eight recognized bariatric surgeons from 28 countries participated in the modified Delphi consensus to vote on 64 statements in two rounds. An agreement/disagreement among ≥ 70.0% of the experts was regarded to indicate a consensus. RESULTS: A consensus was achieved for 46 statements. For recurrent weight gain or worsening of a significant obesity complication after OAGB, more than 85% of experts reached a consensus that elongation of the biliopancreatic limb (BPL) is an acceptable option and the total bowel length measurement is mandatory during BPL elongation to preserve at least 300-400 cm of common channel limb length to avoid nutritional deficiencies. Also, more than 85% of experts reached a consensus on conversion to Roux-en-Y gastric bypass (RYGB) with or without pouch downsizing as an acceptable option for the treatment of persistent bile reflux after OAGB and recommend detecting and repairing any size of hiatal hernia during conversion to RYGB. CONCLUSION: While the experts reached a consensus on several aspects regarding revision/conversion surgeries after OAGB, there are still lingering areas of disagreement. This highlights the importance of conducting further studies in the future to address these unresolved issues.


Assuntos
Consenso , Técnica Delphi , Derivação Gástrica , Obesidade Mórbida , Reoperação , Humanos , Derivação Gástrica/efeitos adversos , Obesidade Mórbida/cirurgia , Redução de Peso , Feminino , Complicações Pós-Operatórias/etiologia , Masculino , Aumento de Peso
8.
Biomed Pharmacother ; 177: 116955, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38906030

RESUMO

OBJECTIVE: Ginsenoside Re, a unique tetracyclic triterpenoid compound found in ginseng, has been suggested in previous reports to improve non-alcoholic fatty liver disease (NAFLD) by modulating lipid imbalance. This study aims to elucidate the potential mechanisms of Ginsenoside Re in treating NAFLD through a combination of bioinformatics analysis and biological experiments. METHODS: Network pharmacology methods were employed to systematically depict the effective components and mechanisms of Ginsenoside Re in improving NAFLD. Molecular docking was utilized to evaluate the binding affinity of Ginsenoside Re with NAFLD-related targets and identify potential targets. NAFLD-related target genes were obtained from the GEO database for gene enrichment analysis, revealing signaling pathways, biological processes, and gene differential expression. Finally, animal experiments were conducted to verify the mechanism of action of Ginsenoside Re in NAFLD. RESULTS: Network pharmacology analysis revealed that Ginsenoside Re improves NAFLD by modulating targets such as AKT1 and TLR4, findings corroborated by molecular docking, GEO database analysis, and experimental validation. Further investigation found that Ginsenoside Re ameliorates lipid metabolism disorders and inflammatory responses induced by NAFLD by modulating the PI3K/AKT and TLR4/NF-κB signaling pathways. CONCLUSION: Our study demonstrates the pharmacological effects of Ginsenoside Re in treating NAFLD, implicating multiple components, targets, and pathways. This provides a solid foundation for considering Ginsenoside Re as an alternative therapy for NAFLD, with promising clinical applications.


Assuntos
Ginsenosídeos , Simulação de Acoplamento Molecular , Hepatopatia Gordurosa não Alcoólica , Transdução de Sinais , Ginsenosídeos/farmacologia , Ginsenosídeos/química , Ginsenosídeos/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Masculino , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Receptor 4 Toll-Like/metabolismo , Farmacologia em Rede , Camundongos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , NF-kappa B/metabolismo , Modelos Animais de Doenças , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia
9.
Research (Wash D C) ; 7: 0382, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38812532

RESUMO

Metabolic dysfunction-associated steatohepatitis (MASH) is the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), and closely associated with a high risk of liver-related morbidity and mortality. Although enhanced neutrophil infiltration of the liver is a histological hallmark of MASH, the morphological pattern of hepatic neutrophils and their relevance to the definition of MASH remain unknown. This clinicopathological study aimed to determine the association of neutrophilic crown-like structures (CLSs) in liver biopsies and evaluate their relevance to the histological diagnosis of MASH. A total of 483 morbidly obese adults who underwent bariatric surgery were recruited. Neutrophilic CLSs in liver biopsies were detected by immunohistochemistry for neutrophil elastase and proteinase 3. All participants were classified into 4 histological subgroups: no MASLD (118, 24.4%), MASLD (76, 15.7%), borderline MASH (185, 38.3%), and definite MASH (104, 21.5%). In the discovery cohort (n = 379), the frequency of neutrophilic CLSs increased in line with the severity of liver disease. The number of neutrophilic CLSs was positively correlated with established histological characteristics of MASH. At a cutoff value of <0.3 per 20× microscopic field, the number of neutrophilic CLSs yielded a robust diagnostic accuracy to discriminate no MASLD and MASLD from borderline MASH and definite MASH; a cutoff at >1.3 per 20× microscopic field exhibited a statistically significant accuracy to distinguish definite MASH from other groups (no MASLD, MASLD, and borderline MASH). The significance of neutrophilic CLSs in identifying borderline MASH and definite MASH was confirmed in an external validation cohort (n = 104). The frequency of neutrophilic CLSs was significantly higher than that of macrophagic CLSs. In conclusion, neutrophilic CLSs in the liver represent a typical histological characteristic of MASH and may serve as a promising indicator to improve the diagnostic accuracy of MASH during histological assessment of liver biopsies.

10.
Obes Surg ; 34(6): 2007-2016, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38652438

RESUMO

BACKGROUND: The role of current pharmacological treatment after laparoscopic sleeve gastrectomy (LSG) is limited. The incidence of postoperative nausea and vomiting (PONV) after LSG remains high. Auricular acupressure (AA) is believed to relieve PONV after laparoscopic surgeries, but its role in patients with obesity after LSG has yet to be confirmed. METHODS: Ninety-five female patients who underwent LSG were randomized into two groups: AA combined with conventional anti-nausea medication (AA group, 47 patients) or conventional anti-nausea medication group (control group, 48 patients). Index of nausea and vomiting and retching (INVR) scores, postoperative anti-vomiting medication use, time of first anus exhausting, time of first fluid intake, and time of first to get out of bed were collected within 48 h after surgery. RESULTS: Demographic data of patients in both groups were balanced and comparable. INVR score (F = 7.505, P = 0.007), vomiting score (F = 11.903, P = 0.001), and retching score (F = 12.098, P = 0.001) were significantly lower in the AA group than that in the control group within 48 h postoperatively. Use of metoclopramide was significantly less in the AA group than in the control group (4.7 [5.5]) vs. 8.8 [7.6], P = 0.004); time to first anus exhausting was significantly less in the AA group than in the control group (17.50 [6.00] vs. 20.42 [8.62], P = 0.020). CONCLUSIONS: AA combined with conventional anti-vomiting agents can alleviate PONV in female patients after LSG, and AA can promote gastrointestinal exhaustion. TRIAL REGISTRATION: The trial has been registered in the Chinese Clinical Trial Registry (ChiCTR) with the registration no. ChiCTR2100047381 on June 13, 2021.


Assuntos
Acupressão , Laparoscopia , Náusea e Vômito Pós-Operatórios , Humanos , Feminino , Náusea e Vômito Pós-Operatórios/epidemiologia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Adulto , Estudos Prospectivos , Acupressão/métodos , Obesidade Mórbida/cirurgia , Gastrectomia , Antieméticos/uso terapêutico , Pessoa de Meia-Idade , Resultado do Tratamento , Recuperação de Função Fisiológica
11.
Obes Surg ; 34(6): 2054-2065, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38662251

RESUMO

OBJECTIVE: This study aimed to evaluate the technical variations of one-anastomosis gastric bypass (OAGB) among IFSO-APC and MENAC experts. BACKGROUND: The multitude of technical variations and patient selection challenges among metabolic and bariatric surgeons worldwide necessitates a heightened awareness of these issues. Understanding different perspectives and viewpoints can empower surgeons performing OAGB to adapt their techniques, leading to improved outcomes and reduced complications. METHODS: The scientific team of IFSO-APC, consisting of skilled bariatric and metabolic surgeons specializing in OAGB, conducted a confidential online survey. The survey aimed to assess technical variations and considerations related to OAGB within the IFSO-APC and IFSO-MENAC chapters. A total of 85 OAGB experts participated in the survey, providing their responses through a 35-question online format. The survey took place from January 1, 2024, to February 15, 2024. RESULTS: Most experts do not perform OAGB for children and adolescents younger than 18 years. Most experts create the gastric pouch over a 36-40-F bougie and prefer to create a gastrojejunostomy, at the posterior wall of the gastric pouch. An anti-reflux suture during OAGB is performed in all patients by 51.8% of experts. Most experts set a common limb length of > 4 m in revisional and conversional OAGBs to prevent nutritional complications. CONCLUSION: The ongoing debate among metabolic and bariatric surgeons regarding the technical variations and patient selection in OAGB remains a significant point of discussion. This survey demonstrated the variations in technical aspects and patient selection for OAGB among MBS surgeons in the IFSO-APC and IFSO-MENAC chapters. Standardizing the OAGB technique is crucial to ensure optimal safety and efficacy in this procedure.


Assuntos
Derivação Gástrica , Obesidade Mórbida , Humanos , Derivação Gástrica/métodos , Obesidade Mórbida/cirurgia , Inquéritos e Questionários , Feminino , Masculino , Seleção de Pacientes , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Adolescente
12.
Gastroenterol Rep (Oxf) ; 12: goae016, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529014

RESUMO

Background: Since boosting stem cell resilience in stressful environments is critical for the therapeutic efficacy of stem cell-based transplantations in liver disease, this study aimed to establish the efficacy of a transient plasmid-based preconditioning strategy for boosting the capability of mesenchymal stromal cells (MSCs) for anti-inflammation/antioxidant defenses and paracrine actions in recipient hepatocytes. Methods: Human adipose mesenchymal stem cells (hADMSCs) were subjected to transfer, either with or without the nuclear factor erythroid 2-related factor 2 (Nrf2)/Dickkopf1 (DKK1) genes, followed by exposure to TNF-α/H2O2. Mouse models were subjected to acute chronic liver failure (ACLF) and subsequently injected with either transfected or untransfected MSCs. These hADMSCs and ACLF mouse models were used to investigate the interaction between Nrf2/DKK1 and the hepatocyte receptor cytoskeleton-associated protein 4 (CKAP4). Results: Activation of Nrf2 and DKK1 enhanced the anti-stress capacity of MSCs in vitro. In a murine model of ACLF, transient co-overexpression of Nrf2 and DKK1 via plasmid transfection improved MSC resilience against inflammatory and oxidative assaults, boosted MSC transplantation efficacy, and promoted recipient liver regeneration due to a shift from the activation of the anti-regenerative IFN-γ/STAT1 pathway to the pro-regenerative IL-6/STAT3 pathway in the liver. Importantly, the therapeutic benefits of MSC transplantation were nullified when the receptor CKAP4, which interacts with DKK1, was specifically removed from recipient hepatocytes. However, the removal of the another receptor low-density lipoprotein receptor-related protein 6 (LRP6) had no impact on the effectiveness of MSC transplantation. Moreover, in long-term observations, no tumorigenicity was detected in mice following transplantation of transiently preconditioned MSCs. Conclusions: Co-stimulation with Nrf2/DKK1 safely improved the efficacy of human MSC-based therapies in murine models of ACLF through CKAP4-dependent paracrine mechanisms.

13.
Oncol Lett ; 27(5): 209, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38549802

RESUMO

Breast cancer (BC) is the most common type of malignancy and the leading cause of cancer-associated mortality in women worldwide. As such, assessing the metabolic changes during human breast carcinogenesis is key for developing disease prevention methods and treatment. In the present study, non-targeted metabolomics with chemometrics based on ultra-high performance liquid chromatography-high-resolution mass spectrometry were performed to assess differences in serum metabolite patterns between patients with BC and healthy individuals. A total of 3,246 metabolites in the sera of healthy controls and patients with BC were found. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that arginine, proline, nicotinate, nicotinamide, caffeine and arachidonic acid metabolism, as well as fatty acid biosynthesis were significantly altered in patients with BC in comparison with controls. These results suggested that serum metabolic profiling has potential for discovering molecular biomarkers for the detection of BC. It may also further the understanding of the underlying mechanisms associated with this disease.

14.
Adv Sci (Weinh) ; 11(18): e2309255, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38429906

RESUMO

Gut microbiota is linked to human metabolic diseases. The previous work showed that leucine deprivation improved metabolic dysfunction, but whether leucine deprivation alters certain specific species of bacterium that brings these benefits remains unclear. Here, this work finds that leucine deprivation alters gut microbiota composition, which is sufficient and necessary for the metabolic improvements induced by leucine deprivation. Among all the affected bacteria, B. coccoides is markedly increased in the feces of leucine-deprived mice. Moreover, gavage with B. coccoides improves insulin sensitivity and reduces body fat in high-fat diet (HFD) mice, and singly colonization of B. coccoides increases insulin sensitivity in gnotobiotic mice. The effects of B. coccoides are mediated by metabolizing tryptophan into indole-3-acetic acid (I3AA) that activates the aryl hydrocarbon receptor (AhR) in the liver. Finally, this work reveals that reduced fecal B. coccoides and I3AA levels are associated with the clinical metabolic syndrome. These findings suggest that B. coccoides is a newly identified bacterium increased by leucine deprivation, which improves metabolic disorders via metabolizing tryptophan into I3AA.


Assuntos
Modelos Animais de Doenças , Microbioma Gastrointestinal , Leucina , Camundongos Endogâmicos C57BL , Animais , Camundongos , Leucina/metabolismo , Microbioma Gastrointestinal/fisiologia , Microbioma Gastrointestinal/genética , Masculino , Doenças Metabólicas/metabolismo , Doenças Metabólicas/microbiologia , Dieta Hiperlipídica , Resistência à Insulina/fisiologia , Triptofano/metabolismo , Ácidos Indolacéticos/metabolismo , Fezes/microbiologia , Clostridiales/metabolismo , Clostridiales/genética , Humanos
16.
Eat Weight Disord ; 29(1): 15, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372804

RESUMO

BACKGROUND: Many studies have covered the prevalence of obesity in different populations. However, studies on the prevalence and predictors of obesity among medical staff are lacking. The aim of our study is to investigate the prevalence of obesity among medical staff and to identify the related predictors. METHODS: Using a snowballing recruitment strategy in the form of an electronic questionnaire, a cross-sectional survey was conducted among 1201 medical staff from cooperative hospitals between January and March 2022. We designed a questionnaire to investigate the participants' demographic, lifestyle, diet, physical activity, and work status. RESULTS: The overall prevalence of obesity was 8.5%, with males (13.7%) having a greater incidence than females (5.7%) (p < 0.001). Multiple logistic regression analyses showed that alcohol drinking (OR, 2.34; 95% CI 1.23-4.42, p = 0.01), sugar-sweetened beverages consumed > 3/week (OR, 2.50; 95% CI 1.02-6.15, p = 0.046), and working a night shift > 1/week (OR, 2.17; 95% CI 1.02-4.61, p = 0.043) were independent predictive factors for obesity in men. For women, having midnight snack having midnight snack (OR, 2.93;95% CI 1.24-6.96, p = 0.015), good sleep quality (OR, 4.47; 95% CI 1.10-21.70, p = 0.038), and working a night shift > 1/week (OR, 3.62; 95% CI 1.73-7.57, p = 0.001) were independently associated with obesity. CONCLUSIONS: Obesity presented a low prevalence among medical staff. Alcohol drinking, drinking sugar-sweetened beverages > 3/week, and night shift > 1/week predicted a higher risk of obesity in males. In females, having midnight snack, good sleep quality, and night shift > 1/week were independently associated with obesity. LEVEL OF EVIDENCE: V, descriptive study.


Assuntos
Corpo Clínico , Obesidade , Masculino , Humanos , Feminino , Estudos Transversais , Projetos Piloto , Obesidade/epidemiologia , China
17.
Obes Surg ; 34(4): 1238-1246, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38393456

RESUMO

BACKGROUND: The outcome of weight loss surgery is related to several factors, and for super-obese patients, the rate of weight loss failure and weight recovery after Roux-en-Y gastric bypass (RYGB) is high. Relevant studies have shown that the weight loss effect also correlates with total small bowel length (TSBL) and biliopancreatic (BP) and Roux limbs. However, there are few studies on the relationship between TSBL and anthropometric parameters, the BP limb, the Roux limb, and weight loss effect, and no relevant reports have been reported in China. OBJECTIVES: The objective was to study the relationship between the total length of the small intestine and anthropometric parameters in the Chinese population. The effect of the Roux limb/biliopancreatic limb (RL/BPL) ratio on weight loss and diabetes remission in RYGB patients 1 year after surgery was evaluated to find the appropriate ratio relationship. METHODS: In this prospective study, 148 patients between the ages of 19 and 68 years who underwent laparoscopic Roux-en-Y gastric bypass were enrolled. Height, weight, BMI, the BP limb, the Roux limb, fasting blood glucose (FBG), etc., were noted. To explore the correlation between the total length of the small intestine and these values. Subsequently, the 148 patients were followed up for 1 year after surgery. The patients diagnosed with T2DM before surgery were screened out, and 56 patients were finally identified according to the postoperative follow-up, in which BPL = 50 cm and RL = 150 cm, 175 cm, and 200 cm, respectively. RL/BPL was divided into 3, 3.5, and 4 groups according to the proportional relationship to explore the relationship between RL/BPL and diabetes remission and weight loss. RESULTS: (1) The study included 148 patients (61 women and 87 men). The mean age was 35.68 ± 10.46 years, weight = 127.46 ± 34.51 kg, height = 167.83 ± 9.16 cm, BMI = 44.94 ± 10.58 kg/m2. The average TSBL value was 714.41 ± 101.08 cm. Linear regression analysis showed that TSBL was positively correlated with height, weight, neck circumference, chest circumference, waist circumference, and Roux limb. (2) Fifty-six patients with T2DM who were followed up 1 year after surgery were divided into three groups. Group 1: BPL = 50 cm, RL = 150 cm (n = 20); group 2: BPL = 50 cm, RL = 175 cm (n = 26); group 3: BPL = 50 cm, RL = 200 cm (n = 10); RL/BPL = 3 was associated with higher weight loss than the other groups. The remission rate of diabetes did not differ between the three groups. CONCLUSIONS: TSBL was positively correlated with height, weight, neck circumference, chest circumference, waist circumference, and Roux limb. The TSBL of males was significantly higher than that of females. Among patients with T2DM who participated in the follow-up 1 year after surgery, RL/BPL = 3 (n = 20) had greater weight loss than the other groups.


Assuntos
Diabetes Mellitus Tipo 2 , Derivação Gástrica , Obesidade Mórbida , Masculino , Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Obesidade Mórbida/cirurgia , Estudos Prospectivos , Intestino Delgado/cirurgia , Circunferência da Cintura , Diabetes Mellitus Tipo 2/cirurgia , Resultado do Tratamento
18.
Obes Rev ; 25(6): e13730, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38424660

RESUMO

This study conducted a bibliometric analysis using the Web of Science Core Collection (WOSCC) to explore the relationship between diabetes mellitus and bariatric surgery (BS) from January 1985 to August 2023. No publications were found between 1985 and 1998. However, from 1998 to 2023, a total of 9,496 English articles were identified, accumulating 291,289 citations (241,563 excluding self-citations) and achieving an H-Index of 197. Leading contributors to the field were the United States, China, and Italy. Noteworthy authors in this area of research included Philip R. Schauer, Wei-Jei Lee, and Carel W. le Roux. The major journals that featured this research were 'Obesity Surgery,' 'Diabetes Care,' and 'Surgery for Obesity and Related Diseases.' The most highly cited article focused on lifestyle, diabetes, and cardiovascular risks 10 years after BS, emphasizing the significant attention given to the nutritional, cardiac, and general internal medicine impacts of diabetes and BS. The increase in research output during the review period indicates a growing interest in the relationship between diabetes and BS, providing a valuable reference for future studies in this evolving field.


Assuntos
Cirurgia Bariátrica , Bibliometria , Diabetes Mellitus , Humanos , Pesquisa Biomédica/tendências , Diabetes Mellitus/epidemiologia , Obesidade/cirurgia , Obesidade/epidemiologia
19.
Comput Struct Biotechnol J ; 23: 791-800, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38318437

RESUMO

Introduction: Metabolic disturbances are major contributors to the onset and progression of non-alcoholic fatty liver disease (NAFLD), which includes a histological spectrum ranging from single steatosis (SS) to non-alcoholic steatohepatitis (NASH). This study aimed to identify serum metabolites and lipids enriched in different histological stages of NAFLD and to explore metabolites/lipids as non-invasive biomarkers in risk prediction of NAFLD and NASH in obese Chinese. Methods: Serum samples and liver biopsies were obtained from 250 NAFLD subjects. Untargeted metabolomic and lipidomic profiling were performed using Liquid Chromatography-Mass Spectrometry. Significantly altered metabolites and lipids were identified by MaAsLin2. Pathway enrichment was conducted with MetaboAnalyst and LIPEA. WGCNA was implemented to construct the co-expression network. Logistic regression models were developed to classify different histological stages of NAFLD. Results: A total of 263 metabolites and 550 lipid species were detected in serum samples. Differential analysis and pathway enrichment analysis revealed the progressive patterns in metabolic mechanisms during the transition from normal liver to SS and to NASH, including N-palmitoyltaurine, tridecylic acid, and branched-chain amino acid signaling pathways. The co-expression network showed a distinct correlation between different triglyceride and phosphatidylcholine species with disease severity. Multiple models classifying NAFLD versus normal liver and NASH versus SS identified important metabolic features associated with significant improvement in disease prediction compared to conventional clinical parameters. Conclusion: Different histological stages of NAFLD are enriched with distinct sets of metabolites, lipids, and metabolic pathways. Integrated algorithms highlight the important metabolic and lipidomic features for diagnosis and staging of NAFLD in obese individuals.

20.
Int J Surg ; 110(4): 2044-2054, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38215263

RESUMO

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a prevalent chronic liver disease among patients with obesity. Bariatric surgery, such as sleeve gastrectomy (SG), shows promise in improving the unfavorable condition of MAFLD. Transient elastography (TE) can be utilized to assess the extent of steatosis and liver fibrosis, providing a noninvasive method for preoperative prediction and postoperative evaluation of MAFLD. This study aims to investigate the effectiveness of TE in diagnosing MAFLD by evaluating liver steatosis and tissue stiffness, as well as assessing the early impact of SG in the treatment of obesity-associated MAFLD. METHODS: In this study, the authors collected preoperative and 6-month postoperative data from patients with obesity who were diagnosed with MAFLD by intraoperative liver biopsy. The patients underwent SG at our hospital between August 2021 and April 2023. The authors estimated the diagnostic accuracy for the steatosis and fibrosis categories using the area under the receiver operating characteristic curve (AUROC). The authors also evaluated the influence of disease prevalence on the positive predictive value and negative predictive value. MAFLD diagnosis was based on the liver steatosis activity and fibrosis scoring system. The authors used univariate and multivariate logistic regression analyses to identify factors contributing to severe MAFLD. To visualize the results, the authors created a nomogram and enhanced it with bootstrap resampling for internal validation. Additionally, the authors plotted receiver operating characteristic and calibration curves. The authors compared preoperative and postoperative data, including general information, laboratory tests, and TE results, to assess the early impact of SG in the treatment of obesity-associated MAFLD. RESULTS: Based on the results of liver biopsy, the AUROC for controlled attenuation parameter (CAP) in identifying steatosis was found to be 0.843 (95% CI: 0.729-0.957) for S≥S1, 0.863 (95% CI: 0.786-0.940) for S≥S2, and 0.872 (95% CI: 0.810-0.934) for S=S3. The Youden limits for S≥S1, S≥S2, and S≥S3 were determined to be 271 dB/m, 292 dB/m, and 301 dB/m, respectively. Similarly, the AUROC for liver stiffness measurement (LSM)/E in detecting liver fibrosis was 0.927 (95% CI: 0.869-0.984) for F≥F2, 0.919 (95% CI: 0.824-0.979) for F≥F3, and 0.949 (95% CI: 0.861-0.982) for F=F4, with Youden cutoff values of 7.5 kPa, 8.3 kPa, and 10.4 kPa, respectively. Patients with A≥3 and/or F≥3 were classified as having severe MAFLD. Multivariate logistic regression analysis identified CAP, E, LDL, and AST as the best diagnostic factors for severe MAFLD, and a nomogram was constructed based on these factors. The AUROC of the nomogram for the assessment of severe MAFLD was 0.824 (95% CI: 0.761-0.887), which was further validated by 1000 bootstrap resamplings with a bootstrap model area under curve of 0.823. Finally, after a 6-month follow-up period, the steatosis grade and fibrosis stage of the patients were graded based on the optimal cutoff values for CAP and LSM. Significant reductions in BMI, waist circumference, HbA1c, fasting glycemia, triglycerides, high density lipoprotein (HDL), glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), gamma glutamyl transpeptidase (GGT), CAP, LSM, steatosis grade, and fibrosis stage were observed compared to the preoperative values. CONCLUSION: In this prospective study, the authors investigated the use of CAP and LSM as alternatives to liver biopsy for evaluating hepatic steatosis and fibrosis in patients with obesity combined with MAFLD. Furthermore, the authors examined the impact of SG on metabolic indicators and the progression of fatty liver disease during the early postoperative period, and observed significant improvements in both aspects.


Assuntos
Técnicas de Imagem por Elasticidade , Gastrectomia , Humanos , Técnicas de Imagem por Elasticidade/métodos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , China/epidemiologia , Estudos Retrospectivos , Cirurgia Bariátrica , Obesidade Mórbida/cirurgia , Obesidade Mórbida/complicações , Fígado Gorduroso/diagnóstico por imagem , Curva ROC , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/cirurgia , Obesidade/complicações , Fígado/diagnóstico por imagem , Fígado/patologia , População do Leste Asiático
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