Activated Liver X Receptors Stimulate Adipocyte Differentiation through Induction of Peroxisome Proliferator-Activated Receptor γ Expression
Open accessAbstract
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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Peripherally, LXRs and PPARγ participate in a coupled metabolic pathway in which activation of PPARγ induces expression of LXRα and its target genes abca1 and apoE.
“Peripherally, LXRs and PPARγ participate in a coupled metabolic pathway, whereby activation of PPARγ induces expression of LXRα and its target genes abca1 and apoE (Chawla et al., 2001; Seo et al., 2004; Yue and Mazzone, 2009).”
From Mechanisms Underlying the Rapid Peroxisome Proliferator-Activated Receptor-γ-Mediated Amyloid Clearance and Reversal of Cognitive Deficits in a Murine Model of Alzheimer's Disease (2012) · cites this paper as Seo et al., 2004
The Discussion (page unavailable) says PPARγ regulates LXRα expression and describes a positive-feedback pathway between the two receptors. An introductory passage indexed as Abstract (page unavailable) says LXR activation promotes cholesterol efflux through ABCA1 and apoE in macrophages. The paper does not establish the full claimed sequence—that activating PPARγ induces expression of LXRα, ABCA1, and apoE. (LLM, conf=0.82)
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“Peripherally, LXRs and PPARγ participate in a coupled metabolic pathway, whereby activation of PPARγ induces expression of LXRα and its target genes abca1 and apoE (Chawla et al., 2001; Seo et al., 2004; Yue and Mazzone, 2009).”
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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
- 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
- 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
- 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
- Health Sciences › Medicine › Surgery › 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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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