ArticleThe Journal of clinical investigation2015
Tribbles-1 regulates hepatic lipogenesis through posttranscriptional regulation of C/EBPα.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 4 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 4 syntheses or guidelines pooled it, 89 citations in OpenAlex.
- Macrophage-associated kinase signaling in atherosclerosis - a systematic review.Cell communication and signaling : CCS · 2026Pooled it
- Genome-wide association meta-analysis identifies 17 loci associated with nonalcoholic fatty liver disease.Nature genetics · 2023Pooled it
- Effect ofCardiovascular therapeutics · 2023Pooled it
- Genetic Landscape of the ACE2 Coronavirus Receptor.Circulation · 2022Pooled it
- Mechanisms and reversal strategies of liver fibrosis: from regulation of cell fate to clinical translation.Journal of translational medicine · 2026Review
- Gene Editing of Pluripotent Stem Cell-Derived Hepatic Cells for Liver Disease Modeling and Therapeutic Development.Biomolecules & therapeutics · 2026Review
- Rosa roxburghii Tratt fruit extract ameliorate free fatty acid induced steatosis in HepG2 cells through activating PI3K-Akt and PPAR pathways.Scientific reports · 2025Article
- DET1 dynamics underlie cooperative ubiquitination by CRL4Science advances · 2025Article
- Distinct roles of Constitutive Photomorphogenesis Protein 1 homolog (COP1) in human hepatocyte models.Frontiers in molecular biosciences · 2025Article
- Exploring the role of alternative lengthening of telomere-related genes in diagnostic modeling for non-alcoholic fatty liver disease.Scientific reports · 2024Article
- Long Noncoding RNA TRIBAL Links the 8q24.13 Locus to Hepatic Lipid Metabolism and Coronary Artery Disease.Circulation. Genomic and precision medicine · 2024Article
- Article
- Review
- Hepatocyte-specific CCAAT/enhancer binding protein α restricts liver fibrosis progression.The Journal of clinical investigation · 2024Article
- The βAdvances in pharmacological and pharmaceutical sciences · 2024Review
- The pseudokinase TRIB3 controls adipocyte lipid homeostasis and proliferation in vitro and in vivo.Molecular metabolism · 2023Article
- Gene Variants Implicated in Steatotic Liver Disease: Opportunities for Diagnostics and Therapeutics.Biomedicines · 2023Review
- Regulation of TRIB1 abundance in hepatocyte models in response to proteasome inhibition.Scientific reports · 2023Article
- C/EBPα promotes triacylglycerol synthesis via regulating PPARG promoter activity in goat mammary epithelial cells.Journal of animal science · 2023Article
- Bioinformatics analysis of the common targets of miR-223-3p, miR-122-5p, and miR-93-5p in polycystic ovarian syndrome.Frontiers in genetics · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
Abstract
Variants near the gene TRIB1 are significantly associated with several plasma lipid traits, circulating liver enzymes, and the development of coronary artery disease in humans; however, it is not clear how its protein product tribbles-1 regulates lipid metabolism. Here, we evaluated mice harboring a liver-specific deletion of Trib1 (Trib1_LSKO) to elucidate the role of tribbles-1 in mammalian hepatic lipid metabolism. These mice exhibited increased hepatic triglyceride (TG) content, lipogenic gene transcription, and de novo lipogenesis. Microarray analysis revealed altered transcription of genes that are downstream of the transcription factor C/EBPα, and Trib1_LSKO mice had increased hepatic C/EBPα protein. Hepatic overexpression of C/EBPα in WT mice phenocopied Trib1_LSKO livers, and hepatic knockout of Cebpa in Trib1_LSKO mice revealed that C/EBPα is required for the increased lipogenesis. Using ChIP-Seq, we found that Trib1_LSKO mice had increased DNA-bound C/EBPα near lipogenic genes and the Trib1 gene, which itself was transcriptionally upregulated by C/EBPα overexpression. Together, our results reveal that tribbles-1 regulates hepatic lipogenesis through posttranscriptional regulation of C/EBPα, which in turn transcriptionally upregulates Trib1. These data suggest an important role for C/EBPα in mediating the lipogenic effects of hepatic Trib1 deletion and provide insight into the association between TRIB1 and plasma lipids, and liver traits in humans.
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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.