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Differential expression of Cyclin G2, Cyclin dependent kinase inhibitor 2C and peripheral myelin protein 22 genes during adipogenesis
Increasing numbers of fat cells in adipose tissue are attributed to proliferation of preadipocytes or immature adipocytes in the early stages, as well as adipogenic differentiation, in the later stages of adipogenesis. Although both events are involved in the increase in fat cell numbers, they are contrary to each other in that the former requires cell cycle activity, whereas the latter requires cell cycle withdrawal. Therefore, appropriate regulation of cell cycle inhibition is critical to adipogenesis. In order to explore the important cell cycle inhibitors and study their expression in adipogenesis, a strategy was adopted that combined the Gene Expression Omnibus (GEO) database on the NCBI website and the results of quantitative real-time PCR (qPCR) analysis of porcine adipose tissue. Three cell cycle inhibitors - Cyclin G2 (CCNG2), Cyclin-dependent kinase inhibitor 2C (CDKN2C), and Peripheral Myelin Protein (PMP22) - were selected for study, because they are relatively highly expressed in adipose tissue compared to muscle, heart, lung, liver, and kidney in humans and mice based on 2 Gene Expression Omnibus Datasets (GDS596 and GDS3142). These genes were found to be more highly expressed in differentiating/differentiated preadipocytes than in undifferentiated preadipocytes in humans and mice as shown by the GDS2366 and GDS2743 datasets, respectively. In addition, the GDS2659 dataset also suggested increasing expression of the 3 cell cycle inhibitors during differentiation of 3T3-L1 cells. Further study with qPCR in Landrace pigs did not confirm the high expression of these genes in adipose tissue compared to other tissues in market-age pigs, but confirmed greater expression of these genes in fat cells than in the stromal vascular fraction, as well as increasing expression of these genes during in vitro adipogenic differentiation and in vivo development of adipose tissue. Moreover, the expression of all 3 genes was reduced by short-term fasting in market-age pigs, but was not restored by short-term refeeding. Based on the analysis of the GEO datasets and qPCR results, we conclude that all 3 cell cycle inhibitors may inhibit adipocyte proliferation, but promote adipocyte differentiation and hold a differentiated state by inducing and maintaining cell cycle inhibition. Therefore, their expression in adipose tissue is positively correlated with age and number of mature fat cells. By regulating expression of these genes, we may be able to control the number of fat cells, and, thus, reduce excessive fat tissue in animals and humans.
Keywords: Adipogenesis, Cell cycle inhibitors, Gene expression