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J. Biol. Chem., Vol. 279, Issue 33, 34840-34848, August 13, 2004

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The Novel Gene fad158, Having a Transmembrane Domain and Leucine-rich Repeat, Stimulates Adipocyte Differentiation^*

Kei Tominaga, Chiharu Kondo, Takeshi Kagata, Tomoaki Hishida, Makoto Nishizuka, and Masayoshi Imagawa¶

From the Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan and Research Division, Nissui Pharmaceutical Co., Ltd., 1075-2 Hokunanmoro, Yuki, Ibaraki 307-0036, Japan

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.

Received for publication, November 26, 2003 , and in revised form, May 11, 2004.

^* This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, by the Japan Society for the Promotion of Science), and by ONO Medical Research Foundation, Japan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed. Tel. and Fax: 81-52-836-3455; E-mail: imagawa{at}phar.nagoya-cu.ac.jp.

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