The role of C/EBPdelta in the early stages of adipogenesis.
Adipocyte differentiation is a complex process triggered and facilitated by transcription factors such as peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer-binding protein (C/EBP) alpha. Most about the cascade underlying the differentiation process, especially events in the early stages, remain to be elucidated. Early on in adipocyte differentiation, the C/EBPbeta and C/EBPdelta genes are rapidly induced to express and later activate PPARgamma and C/EBPalpha expression. C/EBPbeta also plays a crucial role in mitotic clonal expansion (MCE), the approximately two rounds of mitosis which occurs soon after preadipocytes are stimulated by differentiation inducers and a necessary step for adipocyte differentiation. However, the effect of C/EBPdelta, another member of the C/EBP family, on MCE remains unclear. In the present study, we investigated the role of C/EBPdelta in the early stages of adipogenesis. A remarkable induction of C/EBPdelta gene expression after the initiation of differentiation was observed not in proliferating preadipocytes, but in growth-arrested, differentiable cells. RNAi-mediated knockdown of C/EBPdelta dramatically suppressed cell growth after differentiation was induced, and inhibited conversion into lipid-laden adipocytes. Furthermore, silencing of C/EBPdelta impaired the expression of factor for adipocyte differentiation (fad) 49, which is up-regulated and plays a crucial role early in adipogenesis. Taken together, these findings show that C/EBPdelta is involved in MCE and gene expression in the early stages of adipocyte differentiation.
Hishida
Tomoaki
T
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
Nishizuka
Makoto
M
Osada
Shigehiro
S
Imagawa
Masayoshi
M
D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D051379:Mice; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
C533499:Fad49 protein, mouse; D049294:Phospholipid Transfer Proteins; D051743:CCAAT-Enhancer-Binding Protein-delta