Transcription factor HMG box‐containing protein 1 (HBP1) modulates mitotic clonal expansion (MCE) during adipocyte differentiation

Abstract

Transcription factor HMG box-containing protein 1 (HBP1) has been found to be up-regulated in rat adipose tissue and differentiated preadipocyte; however, how HBP1 is involved in adipocyte formation remains unclear. In the present study, we demonstrated that under a standard differentiation protocol HBP1 expression fluctuates with down-regulation in the mitotic clonal expansion (MCE) stage followed by up-regulation in the terminal differentiation stage in both 3T3-L1 and MEF cell models. Also, HBP1 knockdown accelerated cell cycle progression in the MCE stage, but it impaired final adipogenesis. To gain further insight into the role of HBP1 in the MCE stage, we found that the HBP1 expression pattern is reciprocal to that of C/EBPβ, and ectopic expression of HBP1suppresses C/EBPβ expression. These data indicate that HBP1 functions as a negative regulator of MCE. In contrast, when HBP1 expression was gradually elevated along with a concomitant induction of C/EBPα at the end of the MCE, HBP1 knockdown leads to a significant reduction of C/EBPα expression, suggesting that HBP1-mediated C/EBPα expression may be needed for the termination of the cell cycle at the end of MCE for terminal differentiation. All told, our findings show that HBP1 is a key transcription factor in the already complicated regulatory cascade during adipocyte differentiation.

Tigliane Diterpenoids as a New Type of Antiadipogenic Agents Inhibit GRα-Dexras1 Axis in Adipocytes

“…During adipogenesis, the differentiation factors are strictly regulated in a time order. The early differentiation factors C/EBPβ and C/EBPδ are first activated in 2–4 h, whereas the late differentiation factors C/EBPα and PPARγ are activated in 8–24 h . As Dexras1 is an upstream regulator that could activate these differentiation factors in adipogenesis, the levels of Dexras1 upon exposure to adipogenic cocktail and/or 1 and 1a were investigated during the activation of these differentiation factors.…”

“…32 As expected, the stimulation of the cocktail medium in 24 h significantly activated the expression of differentiation factors CCAAT-enhancer-binding protein α, β, and δ (C/EBPα, β, and δ) and peroxisome proliferatoractivated receptor γ (PPARγ) at both transcriptional and translational levels whereas the treatments of 1 and 1a dosedependently decreased the expression of these markers (Figure 4C,D). Correspondingly, the levels of fatty acid synthesisrelated proteins, such as stearoyl-CoA desaturase-1 (SCD1), acetyl CoA carboxylase (ACC), and fatty acid synthase (FAS), 33 As Dexras1 is an upstream regulator that could activate these differentiation factors in adipogenesis, 16 the levels of Dexras1 upon exposure to adipogenic cocktail and/or 1 and 1a were investigated during the activation of these differentiation factors. As shown in Figure 5A, under the stimulation of adipogenic cocktail, the Dexras1 was activated within 24 h and dramatically peaked at 4 h at both transcriptional and translational levels.…”