Distinct Transcriptional Profiles of Adipogenesisin Vivo and in Vitro

Abstract

Obesity, defined as an increase in adipose tissue mass, is the most prevalent nutritional disorder in industrialized countries and is a growing problem in developing countries. An increase in adipose tissue mass can be the result of the production of new fat cells through the process of adipogenesis and/or the deposition of increased amounts of cytoplasmic triglyceride per cell. Although much has been learned about the differentiation of adipocytes in vitro, less is known about the molecular basis for the mechanisms regulating adipogenesis in vivo. Here oligonucleotide microarrays have been used to compare the patterns of gene expression in preadipocytes and adipocytes in vitro and in vivo. These data indicate that the cellular programs associated with adipocyte differentiation are considerably more complex than previously appreciated and that a greater number of heretofore uncharacterized gene regulatory events are activated during this process in vitro. In addition, the gene expression changes associated with adipocyte development in vivo and in vitro, while overlapping, are in some respects quite different. These data further suggest that one or more transcriptional programs are activated exclusively in vivo to generate the full adipocyte phenotype. This gene expression survey now sets the stage for further studies to dissect the molecular differences between in vivo and in vitro adipocytes.

Functional expression of glucose-dependent insulinotropic polypeptide receptors is coupled to differentiation in a human adipocyte model

“…Differentiation studies in 3T3-L1 cells have reported that the expression of mRNA for FABP4 is absent in undifferentiated cells, is detectable by day 3 of differentiation and then rapidly increases towards a steady state around day 8 (several 100-fold increase in gene expression), for up to 28 days. 20,22,27 Similar profiles of FABP4 gene expression have been observed during the differentiation of human marrow and adipose tissue stromal cells into adipocytes, 28,29 as well as during the differentiation of SGBS cells. 16 We specifically analysed the expression profile of FABP4 during the differentiation of SGBS cells to relate GIPR expression to a well-established molecular differentiation marker of adipogenesis.…”

“…15 A number of studies have established that the pattern and time-course of gene expression in SGBS cells during differentiation is comparable to the findings in human preadipocytes in primary culture and also resemble the characteristics of rodent preadipocyte cell lines such as 3T3-L1, 3T3-F442A and ob17. 15,16,[20][21][22][23][24] Differentiated SGBS cells also behave biochemically and functionally like human adipocytes differentiated in primary culture. 15,16,25 In this study, we used these cells to examine the regulation of GIPR expression in the context of the dynamic process of adipocyte differentiation.…”

Grape-seed derived procyanidins interfere with adipogenesis of 3T3-L1 cells at the onset of differentiation

“…Also, microarray-based studies of adipose differentiation have shown that mRNAs maximally expressed at 16-24 h correspond to many genes associated with the cell cycle. 36,[39][40][41] Most of the cell cycle related genes in our microarray were downregulated, which suggests that GSPE-treated cells were not Antiadipogenic effects of procyanidins M Pinent et al in the mitotic clonal expansion phase. Opinions on whether mitotic clonal expansion is necessary to allow adipose differentiation are controversial, 42 but recent studies support the idea that mitotic clonal expansion is required for adipogenesis.…”

“…It has been reported that this nuclear transcription factor (PPARg2) is upregulated during differentiation, with mRNA levels starting to rise at 24 h and remaining stable until the end of the differentiation regimens. 36 Therefore, a higher expression than the controls is a rare feature that suggests that GSPE not only partially inhibits differentiation but also produces other gene expression changes that are not characteristic of the differentiation process. When GSPE treatment was performed 2 or 4 days after induction, cell triglyceride content remained unchanged and morphology and G3PDH activity remained unaffected after GSPE treatment at day 4.…”

Liver X receptor agonists ameliorate TNFα-induced insulin resistance in murine brown adipocytes by downregulating protein tyrosine phosphatase-1B gene expression

“…First, NR1HRα and β are abundantly produced in adipocytes, preferentially in subcutaneous rather than in visceral white adipose tissue [9]. In addition, NR1HR production is regulated by the key adipocyte transcription factor PPARγ either in macrophages and in adipose tissue, and many NR1HR target genes are also highly expressed in adipocytes [10][11][12]. Moreover, ligand activation of NR1HR regulates production of the insulin-responsive glucose transporter solute carrier family 2 (facilitated glucose transporter), member 4 (SLC2A4, formerly known as GLUT4) both in vivo and in murine and human adipocytes, through direct interaction with a conserved NR1HR response element in the Slc2a4 promoter.…”