The appropriate remodeling of extracellular matrix is the key molecular signature in subcutaneous adipose tissue following Roux-en-Y gastric bypass

Abstract Aims We sought to reveal the key molecular signature in subcutaneous adipose tissue (scAT) following Roux-en-Y gastric bypass (RYGB), through bioinformatics analysis and further verification in vivo. Main methods We obtained a transcriptome data of scAT from RYGB and sham-operated rats from the Gene Expression Omnibus. The differentially expressed genes (DEGs) were screened and the DEGs-related Gene ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed. Also, the protein-protein interaction (PPI) network was constructed among the DEGs. Furthermore, we established an experimental rat model to verify the bioinformatics findings. Key findings Using the method of bioinformatics, a total of 602 genes were found to be differentially expressed in scAT between the RYGB group and the sham-operated group. GO analysis showed that DEGs were significantly enriched in extracellular matrix(ECM) -associated functions or processes. KEGG pathway analysis revealed that the protein digestion and absorption pathway and ECM-receptor interaction pathway were the most significantly enriched pathways. The genes encoding ECM components and ECM remodeling-related proteins interact substantially in the PPI network. Then the results of rat experimental verified that the gene expression levels of ECM components(Collagen I and III) and ECM cross-linking related proteins(lysyl oxidase and lysyl oxidase-like 1) decreased and ECM dagradation-related proteins increased in scAT following RYGB. These beneficial results were positively associated with improved insulin resistance (IR). Significance Appropriate ECM remodeling, primarily the reduction of ECM deposition and cross-linking and the increase of ECM dagradation, may be the key molecular signature in scAT following RYGB.