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Integrative analyses of biomarkers and pathways for adipose tissue after bariatric surgery.

ABSTRACT: We explored potential biomarkers and molecular mechanisms regarding multiple benefits after bariatric surgery. Differentially expressed genes (DEGs) for subcutaneous adipose tissue (AT) after bariatric surgery were identified by analyzing two expression profiles from the GEO. Subsequently, enrichment analysis, GSEA, PPI network, and gene-microRNAs and gene-TFs networks were interrogated to identify hub genes and associated pathways. Co-expressed DEGs included one that was up-regulated and 22 that were down-regulated genes. The enrichment analyses indicated that down-regulated DEGs were significantly involved in inflammatory responses. GSEA provided comprehensive evidence that most genes enriched in pro-inflammation pathways, while gene-sets after surgery enriched in metabolism. We identified nine hub genes in the PPI network, most of which were validated as highly expressed and hypomethylated in obesity by Attie Lab Diabetes and DiseaseMeth databases, respectively. DGIdb was also applied to predict potential therapeutic agents that might reverse abnormally high hub gene expression. Bariatric surgery induces a significant shift from an obese pro-inflammatory state to an anti-inflammatory state, with improvement in adipocyte metabolic function - representing key mechanisms whereby AT function improves after bariatric surgery. Our study deepens a mechanistic understanding of the benefits of bariatric surgery and provides potential biomarkers or treatment targets for further research.

SUBMITTER: Liu Y

PROVIDER: S-EPMC7469525 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Bariatric surgery and other therapeutic options for obese patients are often evaluated by the loss of weight, reduction of comorbidities or improved quality of life. However, little is currently known about potential therapy-related changes in the adipose tissue of obese patients. The aim of this study was therefore to quantify fat fraction (FF) and T1 relaxation time by magnetic resonance imaging (MRI) after Roux-en-Y gastric bypass surgery and compare the resulting values with the preoperative ones. Corresponding MRI data were available from 23 patients (16 females and 7 males) that had undergone MRI before (M0) and one month after (M1) bariatric surgery. Patients were 22-59 years old (mean age 44.3 years) and their BMI ranged from 35.7-54.6 kg/m2 (mean BMI 44.6 kg/m2) at M0. Total visceral AT volumes (VVAT-T, in L) were measured by semi-automatic segmentation of axial MRI images acquired between diaphragm and femoral heads. MRI FF and T1 relaxation times were measured in well-defined regions of visceral (VAT) and subcutaneous (SAT) adipose tissue using two custom-made analysis tools. Average BMI values were 45.4 kg/m2 at time point M0 and 42.4 kg/m2 at M1. Corresponding VVAT-T values were 5.94 L and 5.33 L. Intraindividual differences in both BMI and VVAT-T were highly significant (p<0.001). Average relaxation times T1VAT were 303.7 ms at M0 and 316.9 ms at M1 (p<0.001). Corresponding T1SAT times were 283.2 ms and 280.7 ms (p = 0.137). Similarly, FFVAT differences (M0: 85.7%, M1: 83.4%) were significant (p <0.01) whereas FFSAT differences (M0: 86.1, M1: 85.9%) were not significant (p = 0.517). In conclusion, bariatric surgery is apparently not only related to a significant reduction in common parameters of adipose tissue distribution, here BMI and total visceral fat volume, but also significant changes in T1 relaxation time and fat fraction of visceral adipose tissue. Such quantitative MRI measures may potentially serve as independent biomarkers for longitudinal and cross-sectional measurements in obese patients.

Project description:BackgroundBariatric surgery is associated to improvements in obesity-associated comorbidities thought to be mediated by a decrease of adipose inflammation. However, the molecular mechanisms behind these beneficial effects are poorly understood.Methodology/principal findingsWe analyzed RNA-seq expression profiles in adipose tissue from 22 obese women before and 3 months after surgery. Of 15,972 detected genes, 1214 were differentially expressed after surgery at a 5% false discovery rate. Upregulated genes were mostly involved in the basal cellular machinery. Downregulated genes were enriched in metabolic functions of adipose tissue. At baseline, 26 modules of coexpressed genes were identified. The four most stable modules reflected the innate and adaptive immune responses of adipose tissue. A first module reflecting a non-specific signature of innate immune cells, mainly macrophages, was highly conserved after surgery with the exception of DUSP2 and CD300C. A second module reflected the adaptive immune response elicited by T lymphocytes; after surgery, a disconnection was observed between genes involved in T-cell signaling and mediators of the signal transduction such as CXCR1, CXCR2, GPR97, CCR7 and IL7R. A third module reflected neutrophil-mediated inflammation; after surgery, several genes were dissociated from the module, including S100A8, S100A12, CD300E, VNN2, TUBB1 and FAM65B. We also identified a dense network of 19 genes involved in the interferon-signaling pathway which was strongly preserved after surgery, with the exception of DDX60, an antiviral factor involved in RIG-I-mediated interferon signaling. A similar loss of connection was observed in lean mice compared to their obese counterparts.Conclusions/significanceThese results suggest that improvements of the inflammatory state following surgery might be explained by a disruption of immuno-inflammatory cascades involving a few crucial molecules which could serve as potential therapeutic targets.

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Integrative analyses of biomarkers and pathways for adipose tissue after bariatric surgery.

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