Shenzhen Hospital, Southern Medical University , Shenzhen, China.
The Third School of Clinical Medicine, Southern Medical University , Guangzhou, China.
Adipocyte. 2020 Dec;9(1):384-400. doi: 10.1080/21623945.2020.1795434.
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.
我们探讨了减重手术后多种益处的潜在生物标志物和分子机制。通过分析 GEO 中的两个表达谱,鉴定了减重手术后皮下脂肪组织 (AT) 的差异表达基因 (DEGs)。随后,进行了富集分析、GSEA、PPI 网络以及基因-miRNA 和基因-TF 网络分析,以鉴定关键基因和相关通路。共表达的 DEGs 包括一个上调和 22 个下调基因。富集分析表明,下调的 DEGs 显著参与炎症反应。GSEA 提供了全面的证据,表明大多数富集在促炎途径中的基因,而手术后的基因集则富集在代谢途径中。我们在 PPI 网络中确定了 9 个关键基因,其中大多数在 Attie 实验室的糖尿病和疾病甲基化数据库中被验证为肥胖时高表达和低甲基化。DGIdb 还被用于预测可能逆转异常高关键基因表达的潜在治疗药物。减重手术诱导肥胖的促炎状态向抗炎状态的显著转变,改善脂肪细胞代谢功能 - 这代表了减重手术后 AT 功能改善的关键机制。我们的研究深化了对减重手术益处的机制理解,并为进一步的研究提供了潜在的生物标志物或治疗靶点。