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.

Adipocyte differentiation is known to be regulated by a complex array of genes known as master regulators. Using a subtraction method, we previously isolated 102 genes that are expressed in the early stage of adipocyte differentiation. One of these genes named fad158 (factor for adipocyte differentiation 158) seems to be a novel gene, since there is no significantly similar gene listed in databases. Both mouse and human fad158 encode 803 amino acids and contain 4 transmembrane regions and 8 leucine-rich repeat motifs. Expression of fad158 was induced at an early stage in differentiating 3T3-L1 cells and was observed in the skeletal muscle. When the expression was knocked down with an antisense method in 3T3-L1 cells, the accumulation of oil droplets was reduced. Moreover, on overexpression of fad158 in NIH-3T3 cells, which are fibroblasts and do not usually differentiate into adipocytes, stable transformants accumulated oil droplets and showed an elevated expression of adipocyte marker genes, indicating that these cells had differentiated into mature adipocytes. fad158 has the ability to regulate adipocyte differentiation positively, especially at an early stage.