Vertical sleeve gastrectomy triggers fast β-cell recovery upon overt diabetes
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE174194 | GEO | 2021/09/01
REPOSITORIES: GEO
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Project description:Bariatric surgery, an effective treatment for obesity and diabetes, leads to profound remodeling of whole body energy homeostasis. We utilized a mouse model of vertical sleeve gastrectomy (VSG), a common bariatric surgery as a tool to identify novel secreted proteins and peptides that might act as important metabolic regulators. We analyzed gene expression in the stomach and intestines following VSG or sham surgery in diet-induced obese mice and sought to identify differentially regulated genes encoding secreted proteins/peptides.
2017-10-14 | GSE104956 | GEO
Project description:Sleeve gastrectomy (VSG) leads to improvement in hepatic steatosis, associated with weight loss. The aims of this study were to investigate whether VSG leads to weight-loss independent improvements in liver steatosis in mice with diet-induced obesity (DIO); and to transcriptomically profile hepatic changes in mice undergoing VSG. Methods: Mice with DIO were treated with VSG, sham surgery with subsequent food restriction to weight-match to the VSG group (Sham-WM), or sham surgery with return to unrestricted diet (Sham-Ad lib). Hepatic transcriptomics were investigated at the end of the study period and treatment groups were compared with mice undergoing sham surgery only (Sham-Ad lib). Results: VSG led to much greater improvement in liver steatosis than Sham-WM (liver triglyceride mg/mg 2.5 ± 0.1, 2.1 ± 0.2, 1.6 ± 0.1 for Sham-AL, Sham-WM and VSG respectively; p=0.003). Homeostatic model assessment of insulin resistance was improved following VSG only (51.2 ± 8.8, 36.3 ± 5.3, 22.3 ± 6.1 for Sham-AL, Sham-WM and VSG respectively; p=0.03). The glucagon-alanine index, a measure of glucagon resistance, fell with VSG but was significantly increased in Sham-WM (9.8 ± 1.7, 25.8 ± 4.6 and 5.2 ± 1.2 in Sham Ad-lib, Sham-WM and VSG respectively; p=0.0003). Genes downstream of glucagon receptor signalling which govern fatty acid synthesis (Acaca, Acacb, Me1, Acyl, Fasn and Elovl6) were downregulated following VSG but upregulated in Sham-WM. Conclusion: Changes in glucagon sensitivity may contribute to weight-loss independent improvements in hepatic steatosis following VSG.
2024-03-13 | GSE225843 | GEO
Project description:We report the expression profiles of ileal samples extracted from obese male C57Bl6 mice following vertical sleeve gastrectomy or sham surgery, focusing of gene signatures indicative of altered bile acid metabolism. We induced obesity in male C57bl6 mice through a high-fat diet. At 8 weeks, they were submitted to either a vertical sleeve gastrectomy (VSG) or a sham surgery; following surgery VSG mice were fed ad libitum while sham controls were pair-fed (SPF) to the experimental animals. During the four perioperative days, mice were fed a liquid Osmolite diet. Approximately 8 weeks after surgery mice were fasted overnight and gavaged with .5mL Osmolite; after one hour mice were sacrificed and the terminal ileum were extracted. RNA was extracted, quantified, and compared between VSG and SPF experimental groups.
2014-03-27 | E-GEOD-53782 | biostudies-arrayexpress
Project description:Purpose: VSG has leads to a restructuring of WAT anantomy and physiology. The study aimed to understand how the (rhythmic) transcriptome is affected by these changes, especially in regard to metabolism and circadian clock genes. Methods: Animals were fed HFD for approx. 10 weeks to be considered overweight (ca. 35g body weight). 32 animals underwent either sham or VSG surgery. After 3-4 days of postoperative care with liquid diet and analgetic treatment, subcutanous WAT biopsies from Zeitgeber time 1, 7, 13, and 19 were collected 9 days after surgery. mRNA sequencing was conducted with Illumina HiSeq 2000 and rhythm analysis of filtered genes performed with JTK_CYCLE. Results: We found a reduction of cycling genes after VSG (sham: 2,493 vs. VSG: 1,013) in parallel to a reduced amplitude of cycling genes shared between VSG and sham animals (paired t-test p < 0.05) independent of the expression of core clock genes. Genes associated with lipid metabolic pathways (fatty acid breakdown and lipogenesis) showed altered circadian regulation. Conclusions: We found VSG to reorganize WAT rhythmic transcriptome in a specific manner independent of the core clock machinery.
2021-06-21 | GSE162671 | GEO
Project description:We report here the transcriptome of sorted enteroendocrine cells from duodenum, ileum and colon from mice after vertical sleeve gastrectomy or sham operation, weight matched or not. We analyze the effect of region of origin and surgery and gene expression and found that only region of origin had an impact on EEC transcriptome
2018-10-19 | GSE121489 | GEO
Project description:ObjectiveThe effectiveness of bariatric surgery in restoring β-cell function has been described in type-2 diabetes (T2D) patients and animal models for years, whereas the mechanistic underpinnings are largely unknown. The possibility of vertical sleeve gastrectomy (VSG) to rescue far-progressed, clinically-relevant T2D and to promote β-cell recovery has not been investigated on a single-cell level. Nevertheless, characterization of the heterogeneity and functional states of β-cells after VSG is a fundamental step to understand mechanisms of glycaemic recovery and to ultimately develop alternative, less-invasive therapies.MethodsWe performed VSG in late-stage diabetic db/db mice and analyzed the islet transcriptome using single-cell RNA sequencing (scRNA-seq). Immunohistochemical analyses and quantification of β-cell area and proliferation complement our findings from scRNA-seq.ResultsWe report that VSG was superior to calorie restriction in late-stage T2D and rapidly restored normoglycaemia in morbidly obese and overt diabetic db/db mice. Single-cell profiling of islets of Langerhans showed that VSG induced distinct, intrinsic changes in the β-cell transcriptome, but not in that of α-, δ-, and PP-cells. VSG triggered fast β-cell redifferentiation and functional improvement within only two weeks of intervention, which is not seen upon calorie restriction. Furthermore, VSG expanded β-cell area by means of redifferentiation and by creating a proliferation competent β-cell state.ConclusionCollectively, our study reveals the superiority of VSG in the remission of far-progressed T2D and presents paths of β-cell regeneration and molecular pathways underlying the glycaemic benefits of VSG.
| S-EPMC8487975 | biostudies-literature
Project description:Vertical sleeve gastrectomy (VSG) produces sustainable weight loss, remission of type 2 diabetes (T2D), and improvement of nonalcoholic fatty liver disease (NAFLD). However, the molecular mechanisms underlying the metabolic benefits of VSG have remained elusive. We have previously demonstrated that diet-induced obesity leads to chromatin modifications in the liver of mice. We demonstrate here that VSG in C57BL/6J wild-type male mice can reverse these chromatin modifications and thereby impact the expression of key metabolic genes. Genes involved in lipid metabolism, especially omega-6 fatty acid metabolism, are up-regulated in livers of mice after VSG while genes in inflammatory pathways are down-regulated after VSG. Consistent with gene expression changes, regulatory regions near genes involved in inflammatory response displayed decreased chromatin accessibility after VSG. Our results indicate that VSG induces global regulatory changes that impact hepatic inflammatory and lipid metabolic pathways, providing new insight into the mechanisms underlying the beneficial metabolic effects induced by VSG.
2017-07-13 | GSE94842 | GEO
Project description:The gut plays a key role in regulating metabolic health. Dietary factors disrupt intestinal physiology and contribute to obesity and diabetes, whereas bariatric procedures such as vertical sleeve gastrectomy (VSG) cause gut adaptations that induce robust metabolic improvements. However, our understanding of these adaptations at the cellular and molecular levels remains limited. In a validated murine model, we leverage single-cell transcriptomics to determine how VSG impacts different cell lineages of the small intestinal epithelium. We define cell type-specific genes and pathways that VSG rescues from high-fat diet perturbation and characterize additional rescue-independent changes brought about by VSG. We show that Paneth cells have increased expression of the gut peptide Reg3g after VSG. We also find that VSG restores pathways pertaining to mitochondrial respiration and cellular metabolism, especially within crypt-based cells. Overall, our study provides unprecedented molecular resolution of VSG’s therapeutic effects on the gut epithelium.
2024-03-27 | GSE234189 | GEO
Project description:We report here the transcriptome of a population enriched in enteroendocrine cells from human jejunum from patients before or after gastrectomy. We analyze the effect of surgery on gene expression and found very little effect on EEC transcriptome
2018-10-19 | GSE121486 | GEO
Project description:Profiling of the murine peptidome along the gastrointestinal tract and pancreas in vertical sleeve gastrectomy and sham operated mice. The study compares the peptidome of various portions of the GI tract using intact mass spectrometry and database searching. These peptides included most gut hormones including proglucagon derived peptides, PYY, GIP, somatostatin, neurotensin amongst others.
2019-02-09 | PXD011455 | Pride