Cited by 250Peroxisome Proliferator-Activated ReceptorsCholesterol and Lipid MetabolismLipid metabolism and biosynthesis

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Activated Liver X Receptors Stimulate Adipocyte Differentiation through Induction of Peroxisome Proliferator-Activated Receptor γ Expression

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Seo, Jong Bae, Moon, Hyang Mi, Kim, Woo Sik, Lee, Yun Sok, Jeong, Hyun Woo, Yoo, Eung Jae, Ham, Jungyeob, Kang, Heonjoong, Park, Myoung-Gyu, Steffensen, Knut R., Stulnig, Thomas M., Gustafsson, Jan-Åke, Park, Sang Dai, Kim, Jae Bum·2004·Molecular and Cellular Biology

DOI 10.1128/mcb.24.8.3430-3444.2004PMC PMC381668

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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.

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Authors: Seo, J. B., Moon, H. M., Kim, W. S., Lee, Y. S., Jeong, H. W., Yoo, E. J., Ham, J., Kang, H., Park, M.-G., Steffensen, K. R., Stulnig, T. M., Gustafsson, J.-Å., Park, S. D., & Kim, J. B.
Affiliations: Seoul National University (KR)
MDBioAlpha R&D Center
Karolinska Institutet (SE)
Department of Biosciences at Novum, Karolinska Institutet
International Vaccine Institute (KR)
Corresponding author: Kim, Jae Bum
ORCID: Seo, Jong Bae
Moon, Hyang Mi
Kim, Woo Sik
Lee, Yun Sok
Jeong, Hyun Woo
Ham, Jungyeob
Kang, Heonjoong
Steffensen, Knut R.
Stulnig, Thomas M.
Kim, Jae Bum
Venue: Molecular and Cellular Biology
Publisher: Informa UK Limited
Published: 2004-04
Volume: 24
Issue: 8
Pages: 3430-3444
ISSN: 0270-7306 (ISSN-L)
1098-5549
DOI: 10.1128/mcb.24.8.3430-3444.2004
PMC: PMC381668
OpenAlex: W2100448400
Cited by: 250
References: 72
Citations by year: 2026: 1 · 2025: 5 · 2024: 5 · 2023: 5 · 2022: 4 · 2021: 10 · 2020: 5 · 2019: 9 · 2018: 9 · 2017: 7 · 2016: 11 · 2015: 16 · 2014: 16 · 2013: 18 · 2012: 11
FWCI: 6.88
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Molecular and Cellular Biology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords: liver X receptor, adipogenesis, PPARγ, T0901317, lipogenesis, SREBP-1c, Fas, AP-2, histone H3 acetylation, liver X receptor alpha, nuclear receptors, transcriptional regulation
MeSH terms: Liver X Receptors, Adipose Tissue, Animals, Cell Differentiation, Cells, Cultured, DNA-Binding Proteins, Gene Expression Regulation, Humans, Liver, Promoter Regions, Genetic, Protein Binding, RNA, Messenger, Transcription Factors, Stromal Cells, Adipocytes, Receptors, Cytoplasmic and Nuclear, Oligonucleotide Array Sequence Analysis, CCAAT-Enhancer-Binding Proteins, RNA, Small Interfering, Mice, Sterol Regulatory Element Binding Protein 1, Orphan Nuclear Receptors

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Activated Liver X Receptors Stimulate Adipocyte Differentiation through Induction of Peroxisome Proliferator-Activated Receptor γ Expression

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