Abstract
Adipose tissue is the most important energy metabolism and secretion organ, and these functions are conferred during the adipogenesis process. However, the cause and the molecular events underlying adipogenesis are still unclear. In this study, we performed integrated bioinformatics analyses to identify vital genes involved in adipogenesis and reveal potential molecular mechanisms. Five mouse high-throughput expression profile datasets were downloaded from the Gene Expression Omnibus (GEO) database; these datasets contained 24 samples of 3T3-L1 cells during adipogenesis, including 12 undifferentiated samples and 12 differentiated samples. The five datasets were reanalyzed and integrated to select differentially expressed genes (DEGs) during adipogenesis via the robust rank aggregation (RRA) method. Functional annotation of these DEGs and mining of key genes were then performed. We also verified the expression levels of some potential key genes during adipogenesis. A total of 386 consistent DEGs were identified, with 230 upregulated genes and 156 downregulated genes. Gene Ontology (GO) analysis showed that the biological functions of the DEGs primarily included fat cell differentiation, lipid metabolic processes, and cell adhesion. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEGs were mainly associated with metabolic pathways, the peroxisome proliferator-activated receptor (PPAR) signaling pathway, regulation of lipolysis in adipocytes, the tumor necrosis factor (TNF) signaling pathway, and the FoxO signaling pathway. The 30 most closely related genes among the DEGs were identified from the protein–protein interaction (PPI) network and verified by real-time quantification during 3T3-L1 preadipocyte differentiation. In conclusion, we obtained a list of consistent DEGs during adipogenesis through integrated analysis, which may offer potential targets for the regulation of adipogenesis and treatment of adipose dysfunction.
Highlights
When preadipocytes differentiate into mature adipocytes during adipogenesis, adipose tissue gains its specific physiological functions: being the primary storage site for fatty acids and the largest endocrine organ
Enzymes involved in triglyceride metabolism, insulin receptors, and adipocyte-secreted products all show increased activity and quantity, which is necessary for lipid metabolic balance and the inflammatory response
The GSE20696 [7] and GSE93637 [3] expression microarray datasets were standardized, and differentially expressed genes (DEGs) were screened with the limma package (|Log2 fold change| > 1, and corrected p-value < 0.05)
Summary
When preadipocytes differentiate into mature adipocytes during adipogenesis, adipose tissue gains its specific physiological functions: being the primary storage site for fatty acids and the largest endocrine organ. Much of our understanding of adipogenesis comes from in vitro studies of preadipocyte models (e.g., the 3T3-L1 and 3T3-F442A cell lines) [1,2]. Adipogenesis (adipocyte differentiation) is a multistep biological process that is highly controlled. The expression of several transcription factors and adipogenic genes during adipogenesis causes adipocyte development. During the terminal differentiation stage, the cell morphology changes dramatically (from fibroblastic to spherical), and preadipocytes synchronously gain the characteristics of mature adipocytes. In the past few decades, a number of regulatory factors related to adipogenic programs have been gradually unearthed
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