Temporal Changes in Gene Expression Profile during Mature Adipocyte Dedifferentiation

摘要

Objective. To characterize changes in gene expression profile during human mature adipocyte dedifferentiation in ceiling culture.Methods. Subcutaneous (SC) and omental (OM) adipose tissue samples were obtained from 4 participants paired for age and BMI.Isolated adipocytes were dedifferentiated in ceiling culture. Gene expression analysis at days 0, 4, 7, and 12 of the cultures wasperformed using Affymetrix Human Gene 2.0 STvi arrays. Hierarchical clustering according to similarity of expression changeswas used to identify overrepresented functions. Results. Four clusters gathered genes with similar expression between day 4 to day7 but decreasing expression from day 7 to day 12. Most of these genes coded for proteins involved in adipocyte functions (LIPE,PLIN1, DGAT2, PNPLA2, ADIPOQ, CEBPA, LPL, FABP4, SCD, INSR, and LEP). Expression of several genes coding for proteinsimplicated in cellular proliferation and growth or cell cycle increased significantly from day 7 to day 12 (WNT5A, KITLG, andFGF5). Genes coding for extracellular matrix proteins were differentially expressed between days 0, 4, 7, and 12 (COL1A1, COL1A2,andCOL6A3,MMP1,andTGFB1).Conclusion.Dedifferentiationisassociatedwithdownregulationoftranscriptsencodingproteinsinvolved in mature adipocyte functions and upregulation of genes involved in matrix remodeling, cellular development, and cellcycle.