Bioinformatics analysis of candidate genes and potential therapeutic drugs targeting adipose tissue in obesity

Abstract

Obesity is a complex medical condition that affects multiple organs in the body. However, the underlying mechanisms of obesity, as well as its treatment, are largely unexplored . The focus of this research was to use bioinformatics to discover possible treatment targets for obesity. To begin, the GSE133099 database was used to identify 364 differentially expressed genes (DEGs). Then, DEGs were subjected to tissue-specific analyses and enrichment analyses, followed by the creation of a protein-protein interaction (PPI) network and generation of a drug-gene interaction database to screen key genes and potential future drugs targeting obesity. Findings have illustrated that the tissue-specific expression of neurologic markers varied significantly (34.7%, 52/150). Among these genes, Lep, ApoE, Fyn, and FN1 were the key genes observed in the adipocyte samples from obese patients relative to the controls. Furthermore, nine potential therapeutic drugs (dasatinib, ocriplasmin, risperidone, gemfibrozil, ritonavir, fluvastatin, pravastatin, warfarin, atorvastatin) that target the key genes were also screened and selected. To conclude the key genes discovered (Lep, ApoE, Fyn, and FN1), as well as 9 candidate drugs, could be used as therapeutic targets in treating obesity.

Identification of crucial modules and genes associated with backfat tissue development by WGCNA in Ningxiang pigs

“…FN1 knockout adversely affects the adipogenic differentiation of induced human infrapatellar fat pad-derived stem cells, as evidenced by remarkably low adipogenic gene expressions and lipid droplets ( Wang et al, 2019 ). Our findings were corroborated by KEGG and protein-protein interaction network analysis, which presented FN1 as a hub gene in subcutaneous adipose tissue derived adipocyte of obese patients; consequently, FN1 and its associated signaling pathways could be rendered potential targets in treating obesity ( Yu et al, 2022 ). Decorin (DCN), a small leucine rich proteoglycan component of the ECM in various tissues, is overexpressed in adipose tissue, binds to a variety of collagens, and contributes to collagen fibril formation ( Meissburger et al, 2016 ; Svärd et al, 2019 ).…”

“…Fibronectin ( FN ), one of the major fibrillary components of the ECM and an adipocyte-specific dysregulated gene product in obese adipose tissue, plays a vital role in tissue development, cell morphology, and mesenchymal stem cell differentiation ( Wang et al, 2019 ; Yu et al, 2022 ). FN1 knockout adversely affects the adipogenic differentiation of induced human infrapatellar fat pad-derived stem cells, as evidenced by remarkably low adipogenic gene expressions and lipid droplets ( Wang et al, 2019 ).…”

“…Collagens expressed by adipose tissue, namely COL1A1, COL1A2, COL5A1, COL6A3, and COL14A1 ( Ullah et al, 2013 ; Côté et al, 2017 ; Yu et al, 2022 ), are key constituents of the ECM and play crucial roles in regulating stem cell stemness, preadipocyte differentiation and adipose tissue expandability ( Berger et al, 2015 ; Wang et al, 2019 ; Johnston and Abbott, 2022 ).…”

“…GO analysis demonstrated that these three DEGs are enriched in ECM organization in biological process; in ECM and collagen trimer in cellular component. KEGG pathway enrichment further revealed that the aforementioned three DEGs are primarily involved in ECM-receptor interaction, protein digestion and absorption, and PI3K-Akt signaling pathway ( Yu et al, 2022 ). These results are in accordance with those of our investigation, although the functional relevance of COL1A1 , COL1A2 , COL5A1 , COL6A3 , and adipogenesis needs to be further elucidated.…”

Alternative Methods as Tools for Obesity Research: In Vitro and In Silico Approaches

“…For example, Yu and collaborators (2022) used a microarray dataset comprising obese and healthy patients to identify differentially expressed genes and enable targeted drug screening. The authors used a drug-gene interaction database that pointed out potential candidates for anti-obesity therapy, such as lipid-modifying drugs like gemfibrozil, fluvastatin, pravastatin, and atorvastatin [ 66 ].…”