ArticleThe Journal of biological chemistry2014
Ursodeoxycholic acid inhibits liver X receptor α-mediated hepatic lipogenesis via induction of the nuclear corepressor SMILE.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Bile acids in metabolic dysfunction-associated steatotic liver disease.World journal of hepatology · 2025Review
- Activation of CTU2 expression by LXR promotes the development of hepatocellular carcinoma.Cell biology and toxicology · 2024Article
- Emerging Role of SMILE in Liver Metabolism.International journal of molecular sciences · 2023Review
- SMILE Downregulation during Melanogenesis Induces MITF Transcription in B16F10 Cells.International journal of molecular sciences · 2022Article
- Ursodeoxycholic acid reduces antitumor immunosuppression by inducing CHIP-mediated TGF-β degradation.Nature communications · 2022Article
- Oxidative Stress, Genomic Integrity, and Liver Diseases.Molecules (Basel, Switzerland) · 2022Review
- Epigallocatechin-3-Gallate Suppresses BMP-6-Mediated SMAD1/5/8 Transactivation of Hepcidin Gene by Inducing SMILE in Hepatocytes.Antioxidants (Basel, Switzerland) · 2021Article
- Lyophilized Maqui (Antioxidants (Basel, Switzerland) · 2021Article
- Natural Products Targeting Liver X Receptors or Farnesoid X Receptor.Frontiers in pharmacology · 2021Review
- Oral Administration of Germinated, Pigmented, Giant Embryo Rice (Oxidative medicine and cellular longevity · 2021Article
- Epigallocatechin-3-Gallate (EGCG)-Inducible SMILE Inhibits STAT3-Mediated Hepcidin Gene Expression.Antioxidants (Basel, Switzerland) · 2020Article
- Neddylation of sterol regulatory element-binding protein 1c is a potential therapeutic target for nonalcoholic fatty liver treatment.Cell death & disease · 2020Article
- Ursodeoxycholic acid ameliorates hepatic lipid metabolism in LO2 cells by regulating the AKT/mTOR/SREBP-1 signaling pathway.World journal of gastroenterology · 2019Article
- Sesamin, a Naturally Occurring Lignan, Inhibits Ligand-Induced Lipogenesis through Interaction with Liver X Receptor Alpha (LXREvidence-based complementary and alternative medicine : eCAM · 2019Article
- Endocrine-disrupting chemicals and fatty liver disease.Nature reviews. Endocrinology · 2017Review
- Article
- Ligands of Therapeutic Utility for the Liver X Receptors.Molecules (Basel, Switzerland) · 2017Review
- Activation of liver X receptor/retinoid X receptor pathway ameliorates liver disease in Atp7B(-/-) (Wilson disease) mice.Hepatology (Baltimore, Md.) · 2016Article
- Article
- Ajuba Preferentially Binds LXRα/RXRγ Heterodimer to Enhance LXR Target Gene Expression in Liver Cells.Molecular endocrinology (Baltimore, Md.) · 2015Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small heterodimer partner interacting leucine zipper protein (SMILE) has been identified as a nuclear corepressor of the nuclear receptor (NRs) family. Here, we examined the role of SMILE in the regulation of nuclear receptor liver X receptor (LXR)-mediated sterol regulatory element binding protein-1c (SREBP-1c) gene expression. We found that SMILE inhibited T0901317 (T7)-induced transcriptional activity of LXR, which functions as a major regulator of lipid metabolism by inducing SREBP-1c, fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) gene expression. Moreover, we demonstrated that SMILE physically interacts with LXR and represses T7-induced LXR transcriptional activity by competing with coactivator SRC-1. Adenoviral overexpression of SMILE (Ad-SMILE) attenuated fat accumulation and lipogenic gene induction in the liver of T7 administered or of high fat diet (HFD)-fed mice. Furthermore, we investigated the mechanism by which ursodeoxycholic acid (UDCA) inhibits LXR-induced lipogenic gene expression. Interestingly, UDCA treatment significantly increased SMILE promoter activity and gene expression in an adenosine monophosphate-activated kinase-dependent manner. Furthermore, UDCA treatment repressed T7-induced SREBP-1c, FAS, and ACC protein levels, whereas knockdown of endogenous SMILE gene expression by adenovirus SMILE shRNA (Ad-shSMILE) significantly reversed UDCA-mediated repression of SREBP-1c, FAS, and ACC protein levels. Collectively, these results demonstrate that UDCA activates SMILE gene expression through adenosine monophosphate-activated kinase phosphorylation, which leads to repression of LXR-mediated hepatic lipogenic enzyme gene expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.