Dataset Information

Bariatric Surgery Modulates Urinary Levels of MicroRNAs Involved in the Regulation of Renal Function.

ABSTRACT: Background: Obesity and diabetes cause chronic kidney disease with a common pathophysiology that is characterized by the accumulation of collagen in the extracellular matrix. Recent evidence has implicated the epithelial-to-mesenchymal transition (EMT) as a key step in this pathology with regulation by microRNAs. Weight loss leads to improvements in renal function; therefore, this study hypothesized that bariatric-surgery aided weight loss would lead to changes in urinary microRNAs involved in the regulation of renal function. Materials and methods: Twenty-four bariatric patients undergoing Roux-en-Y gastric bypass and sleeve gastrectomy donated urine pre-operatively and at 2-6 months and 1-2 years post-operatively. Urine samples were also obtained from 10 healthy weight and 7 morbidly obese non-surgical controls. Expression levels of kidney microRNAs were assessed in urine and the function of microRNAs was assessed through the in vitro transfection of HK-2 cells, a kidney proximal tubule cell line. Results: Levels of miR 192, miR 200a, and miR 200b were upregulated in urine following bariatric surgery. This increase was consistent across surgical type and diabetes status and was maintained and enhanced with time. Bariatric surgery alters urinary miR 192 expression from levels seen in morbidly obese patients to levels seen in healthy weight control patients. In mechanistic studies, the transfection of miR 192 in HK-2 cells increased miR 200a expression and decreased ZEB2, a key transcriptional promoter of kidney fibrosis. Conclusions: Bariatric surgery increased miR 192 and miR 200 urinary levels, key anti-fibrotic microRNAs that could contribute to a renal-protective mechanism and may be of value as urinary biomarkers following surgery. These findings suggest that urinary microRNAs may represent potential novel biomarkers for obesity-associated renal function.

SUBMITTER: Alkandari A

PROVIDER: S-EPMC6536704 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Bariatric Surgery Modulates Urinary Levels of MicroRNAs Involved in the Regulation of Renal Function.

Alkandari Abdullah A Ashrafian Hutan H Sathyapalan Thozhukat T Darzi Ara A Holmes Elaine E Athanasiou Thanos T Atkin Stephen L SL Gooderham Nigel J NJ

Frontiers in endocrinology 20190521

<b>Background:</b> Obesity and diabetes cause chronic kidney disease with a common pathophysiology that is characterized by the accumulation of collagen in the extracellular matrix. Recent evidence has implicated the epithelial-to-mesenchymal transition (EMT) as a key step in this pathology with regulation by microRNAs. Weight loss leads to improvements in renal function; therefore, this study hypothesized that bariatric-surgery aided weight loss would lead to changes in urinary microRNAs involv ...[more]

PMID: 31164867

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Project description:ImportanceAmong women and men with severe obesity, evidence for improvement in urinary incontinence beyond the first year after bariatric surgery-induced weight loss is lacking.ObjectivesTo examine change in urinary incontinence before and after bariatric surgery and to identify factors associated with improvement and remission among women and men in the first 3 years after bariatric surgery.Design, setting, and participantsThe Longitudinal Assessment of Bariatric Surgery 2 is an observational cohort study at 10 US hospitals in 6 geographically diverse clinical centers. Participants were recruited between February 21, 2005, and February 17, 2009. Adults undergoing first-time bariatric surgical procedures as part of clinical care by participating surgeons between March 14, 2006, and April 24, 2009, were followed up for 3 years (through October 24, 2012).InterventionParticipants undergoing bariatric surgery completed research assessments before the procedure and annually thereafter.Main outcomes and measuresThe frequency and type of urinary incontinence episodes in the past 3 months were assessed using a validated questionnaire. Prevalent urinary incontinence was defined as at least weekly urinary incontinence episodes, and remission was defined as change from prevalent urinary incontinence at baseline to less than weekly urinary incontinence episodes at follow-up.ResultsOf 2458 participants, 1987 (80.8%) completed baseline and follow-up assessments. At baseline, the median age was 47 years (age range, 18-78 years), the median body mass index was 46 kg/m2 (range, 34-94 kg/m2), and 1565 of 1987 (78.8%) were women. Urinary incontinence was more prevalent among women (49.3%; 95% CI, 46.9%-51.9%) than men (21.8%; 95% CI, 18.2%-26.1%) (P < .001). After a mean 1-year weight loss of 29.5% (95% CI, 29.0%-30.1%) in women and 27.0% (95% CI, 25.9%-28.6%) in men, year 1 urinary incontinence prevalence was significantly lower among women (18.3%; 95% CI, 16.4%-20.4%) and men (9.8%; 95% CI, 7.2%-13.4%) (P < .001 for all). The 3-year prevalence was higher than the 1-year prevalence for both sexes (24.8%; 95% CI, 21.8%-26.5% among women and 12.2%; 95% CI, 9.0%-16.4% among men) but was substantially lower than baseline (P < .001 for all). Weight loss was independently related to urinary incontinence remission (relative risk, 1.08; 95% CI, 1.06-1.10 in women and 1.07; 95% CI, 1.02-1.13 in men) per 5% weight loss, as were younger age and the absence of a severe walking limitation.Conclusions and relevanceAmong women and men with severe obesity, bariatric surgery was associated with substantially reduced urinary incontinence over 3 years. Improvement in urinary incontinence may be an important benefit of bariatric surgery.

Project description:BackgroundChanges 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.MethodsWe 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.ResultsA 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.ConclusionsShort-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 registrationChiCTR2200058333.

Project description:BackgroundNonalcoholic steatohepatitis (NASH) is the advanced stage of nonalcoholic fatty liver disease (NAFLD), one of the most prevalent chronic liver diseases. The effectiveness of bariatric surgery in treating NASH and preventing or even reversing liver fibrosis has been demonstrated in numerous clinical studies, but the underlying mechanisms and crucial variables remain unknown.MethodsUsing the GSE135251 dataset, we examined the gene expression levels of NASH and healthy livers. Then, the differentially expressed genes (DEGs) of patients with NASH, at baseline and one year after bariatric surgery, were identified in GSE83452. We overlapped the hub genes performed by protein-protein interaction (PPI) networks and DEGs with different expression trends in both datasets to obtain key genes. Genomic enrichment analysis (GSEA) and genomic variation analysis (GSVA) were performed to search for signaling pathways of key genes. Meanwhile, key molecules that regulate the key genes are found through the construction of the ceRNA network. NASH mice were induced by a high-fat diet (HFD) and underwent sleeve gastrectomy (SG). We then cross-linked the DEGs in clinical and animal samples using quantitative polymerase chain reaction (qPCR) and validated the key genes.ResultsSeven key genes (FASN, SCD, CD68, HMGCS1, SQLE, CXCL10, IGF1) with different expression trends in GSE135251 and GSE83452 were obtained with the top 30 hub genes selected by PPI. The expression of seven key genes in mice after SG was validated by qPCR. Combined with the qPCR results from NASH mice, the four genes FASN, SCD, HMGCS1, and CXCL10 are consistent with the biological analysis. The GSEA results showed that the 'cholesterol homeostasis' pathway was enriched in the FASN, SCD, HMGCS1, and SQLE high-expression groups. The high-expression groups of CD68 and CXCL10 were extremely enriched in inflammation-related pathways. The construction of the ceRNA network obtained microRNAs and ceRNAs that can regulate seven key genes expression.ConclusionIn summary, this study contributes to our understanding of the mechanisms by which bariatric surgery improves NASH, and to the development of potential biomarkers for the treatment of NASH.

Project description:BackgroundGrowing evidence has shown that obesity is associated with poor neurocognitive outcomes. Bariatric surgery has been shown to be an effective intervention for morbid obesity and can result in improvement of many co-morbid medical conditions that are associated with cognitive dysfunction. The effects of bariatric surgery on cognition are unknown.MethodsWe performed a prospective study total of 150 subjects (109 bariatric surgery patients enrolled in the Longitudinal Assessment of Bariatric Surgery project and 41 obese control subjects who had not undergone bariatric surgery). These 150 subjects completed a cognitive evaluation at baseline and at 12 weeks of follow-up. The demographic, medical, and psychosocial information was also collected to elucidate the possible mechanisms of change.ResultsMany bariatric surgery patients exhibited impaired performance on cognitive testing at baseline (range 4.6-23.9%). However, the surgery patients were no more likely to exhibit a decline on ?2 cognitive tests at 12 weeks of follow-up than were the obese controls [12.84% versus 23.26%; chi-square (1) = 2.51, P = .11]. Group comparisons using repeated measures multivariate analysis of variance showed that the surgery patients had improved memory performance at 12 weeks of follow-up [? = .86, F(4, 147) = 5.88, P <.001]; however, the memory performance of the obese controls had actually declined. Regression analyses showed that the surgery patients without hypertension had better short delay recall at 12 weeks than those with hypertension [? = .31, P = .005], although the other demographic and medical variables were largely unrelated to the test performance.ConclusionThe present results suggest that cognitive impairment is common in bariatric surgery patients, although these deficits might be at least partly reversible. Future studies are needed to clarify the underlying mechanisms, in particular, longitudinal studies using neuroimaging and blood markers.

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Bariatric Surgery Modulates Urinary Levels of MicroRNAs Involved in the Regulation of Renal Function.

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Bariatric Surgery Modulates Urinary Levels of MicroRNAs Involved in the Regulation of Renal Function.

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