No abstract

Adipocyte differentiation is controlled by complex actions involving gene expression and signal transduction. From metaphase to anaphase, peroxisome proliferator-activated receptor γ, the CCAAT/enhancer-binding protein family and sterol regulatory element-binding protein-1 are known to function as master regulators. However, the mechanism underlying the earliest step, which triggers the initiation of differentiation, remains unknown. In previous reports, we have isolated a number of genes, whose expression increases in the early stage of differentiation in the mouse 3T3-L1 preadipocyte cell line. Here we report the cloning of the full-length cDNA and characterization of an unknown gene isolated previously and named fad24 (factor for adipocyte differentiation 24). Fad24 encodes a protein consisting of 807 amino acids. The deduced amino acid sequence was shown to have a basic leucine zipper motif and a NOC domain. Expression of fad24 was rapidly induced after stimulation with inducers. Furthermore, overexpression of fad24 in NIH-3T3 cells promoted adipogenesis in the presence of a ligand for peroxisome proliferator-activated receptor γ. FAD24 localizes in the nucleus, especially within nuclear speckles. As the nuclear speckle functions as a nascent transcription and pre-mRNA splicing machinery, there is a possibility that FAD24 functions as one of the components for transcription and/or pre-mRNA splicing and positively regulates adipocyte differentiation.

A novel gene named fad104 (factor for adipocyte differentiation-104), whose expression level quickly increased in the early stage of adipogenesis, was isolated and characterized. The deduced amino acid sequence of fad104 revealed the possible presence of a fibronectin type III domain and transmembrane domain. The expression of fad104 was detected in adipocyte differentiable 3T3-L1 cells but not observed in the non-adipogenic cell line NIH-3T3. Moreover, the ability of 3T3-L1 cells to differentiate declined with the knockdown of fad104 by RNA interference, strongly indicating that fad104 functions as a positive regulator of adipogenesis.