title: Activated liver X receptors stimulate adipocyte differentiation through induction of peroxisome proliferator-activated receptor gamma expression.
abstract: 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 PPARgamma (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 PPARgamma gene is a novel target gene of LXR, since the PPARgamma promoter contains the conserved binding site of LXR and was transactivated by the expression of LXRalpha. Moreover, activated LXRalpha exhibited an increase of DNA binding to its target gene promoters, such as ADD1/SREBP1c and PPARgamma, which appeared to be closely associated with hyperacetylation of histone H3 in the promoter regions of those genes. Furthermore, the suppression of LXRalpha 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.
authors.affiliation: School of Biological Sciences. Marine Biotechnology Laboratory, School of Earth and Environmental Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Jong Bae
authors.initials: JB
authors.lastname: Seo
authors.forename: Hyang Mi
authors.initials: HM
authors.lastname: Moon
authors.forename: Woo Sik
authors.initials: WS
authors.lastname: Kim
authors.forename: Yun Sok
authors.initials: YS
authors.lastname: Lee
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Jeong
authors.forename: Eung Jae
authors.initials: EJ
authors.lastname: Yoo
authors.forename: Jungyeob
authors.initials: J
authors.lastname: Ham
authors.forename: Heonjoong
authors.initials: H
authors.lastname: Kang
authors.forename: Myoung-Gyu
authors.initials: MG
authors.lastname: Park
authors.forename: Knut R
authors.initials: KR
authors.lastname: Steffensen
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Stulnig
authors.forename: Jan-Ake
authors.initials: JA
authors.lastname: Gustafsson
authors.forename: Sang Dai
authors.initials: SD
authors.lastname: Park
authors.forename: Jae Bum
authors.initials: JB
authors.lastname: Kim
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000502:physiology*; D000273:Adipose Tissue / Q000166:cytology / Q000502:physiology; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D057093:Orphan Nuclear Receptors; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; C497387:SREBF1 protein, human; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors