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Molecular and Cellular Biology, April 2004, p. 3430-3444, Vol. 24, No. 8
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.8.3430-3444.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Activated Liver X Receptors Stimulate Adipocyte Differentiation through Induction of Peroxisome Proliferator-Activated Receptor {gamma} Expression

Jong Bae Seo,1 Hyang Mi Moon,1 Woo Sik Kim,1 Yun Sok Lee,1 Hyun Woo Jeong,1 Eung Jae Yoo,1 Jungyeob Ham,2 Heonjoong Kang,2 Myoung-Gyu Park,3 Knut R. Steffensen,4 Thomas M. Stulnig,4 Jan-Åke Gustafsson,4 Sang Dai Park,5 and Jae Bum Kim1*

School of Biological Sciences,1 Marine Biotechnology Laboratory, School of Earth and Environmental Sciences, Seoul National University, Seoul 151-742,2 MDBioAlpha R&D Center, Sungnam 462-120,3 International Vaccine Institute, Seoul 151-818, Korea,5 Department of Biosciences at Novum, Karolinska Institutet, Huddinge, Sweden4

Received 22 September 2003/ Returned for modification 5 November 2003/ Accepted 19 January 2004

Liver X receptors (LXRs) are nuclear hormone receptors that regulate cholesterol and fatty acid metabolism in liver tissue and in macrophages. Although LXR activation enhances lipogenesis, it is not well understood whether LXRs are involved in adipocyte differentiation. Here, we show that LXR activation stimulated the execution of adipogenesis, as determined by lipid droplet accumulation and adipocyte-specific gene expression in vivo and in vitro. In adipocytes, LXR activation with T0901317 primarily enhanced the expression of lipogenic genes such as the ADD1/SREBP1c and FAS genes and substantially increased the expression of the adipocyte-specific genes encoding PPAR{gamma} (peroxisome proliferator-activated receptor {gamma}) and aP2. Administration of the LXR agonist T0901317 to lean mice promoted the expression of most lipogenic and adipogenic genes in fat and liver tissues. It is of interest that the PPAR{gamma} gene is a novel target gene of LXR, since the PPAR{gamma} promoter contains the conserved binding site of LXR and was transactivated by the expression of LXR{alpha}. Moreover, activated LXR{alpha} exhibited an increase of DNA binding to its target gene promoters, such as ADD1/SREBP1c and PPAR{gamma}, which appeared to be closely associated with hyperacetylation of histone H3 in the promoter regions of those genes. Furthermore, the suppression of LXR{alpha} by small interfering RNA attenuated adipocyte differentiation. Taken together, these results suggest that LXR plays a role in the execution of adipocyte differentiation by regulation of lipogenesis and adipocyte-specific gene expression.

* Corresponding author. Mailing address: School of Biological Sciences, Seoul National University, San 56-1, Sillim-Dong, Kwanak-Gu, Seoul 151-742, Korea. Phone: 82-2-880-5852. Fax: 82-2-878-5852. E-mail: jaebkim{at}snu.ac.kr.

Molecular and Cellular Biology, April 2004, p. 3430-3444, Vol. 24, No. 8
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.8.3430-3444.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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