ArticleeLife2016
Hedgehog signaling is a potent regulator of liver lipid metabolism and reveals a GLI-code associated with steatosis.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Genome-wide association study of serum liver enzymes implicates diverse metabolic and liver pathology.Nature communications · 2021Pooled it
- Primary cilia: sensors of biliary homeostasis and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Primary cilium as a sensory organelle and metabolic hub in health and diseases.Journal of biomedical science · 2026Review
- Hedgehog/GLI Signaling at the Interface of Sterol Metabolism, Mitochondrial ROS Signaling and Cellular Plasticity.Antioxidants (Basel, Switzerland) · 2026Review
- Hedgehog Signaling Regulates Hypoxia-Associated Metabolic Adaptation in Myeloid Leukemia In Vitro Cell Models.International journal of molecular sciences · 2026Article
- Hepatic management of toxic sterols after acute deletion of Cyp51 from cholesterol synthesis.The Journal of biological chemistry · 2026Article
- Zonation, Zonation, Zonation: The Real Estate of the Liver.Annual review of pathology · 2026Review
- Single-Cell Multiome Impact of Prenatal Heavy Metal Exposure on Early Airway Development.American journal of respiratory cell and molecular biology · 2026Article
- Article
- Impact of Hedgehog modulators on signaling pathways in primary murine and human hepatocytes in vitro: insights into liver metabolism.Archives of toxicology · 2025Article
- Non-cell-autonomous regulation of mTORC2 by Hedgehog signaling maintains lipid homeostasis.Cell reports · 2025Article
- Diagnostic lncRNA biomarkers and immune-related ceRNA networks for osteonecrosis of the femoral head in metabolic syndrome identified by plasma RNA sequencing and machine learning.Frontiers in immunology · 2025Article
- β-Carotene Impacts the Liver MicroRNA Profile in a Sex-Specific Manner in Mouse Offspring of Western Diet-Fed Mothers: Results from Microarray Analysis by Direct Hybridization.International journal of molecular sciences · 2024Article
- Sonic hedgehog-heat shock protein 90β axis promotes the development of nonalcoholic steatohepatitis in mice.Nature communications · 2024Article
- Homeostatic control of stearoyl desaturase expression via patched-like receptor PTR-23 ensures the survival of C. elegans during heat stress.PLoS genetics · 2023Article
- The impact and role of identified long noncoding RNAs in nonalcoholic fatty liver disease: A narrative review.Journal of clinical laboratory analysis · 2023Review
- Circulating indian hedgehog is a marker of the hepatocyte-TAZ pathway in experimental NASH and is elevated in humans with NASH.JHEP reports : innovation in hepatology · 2023Article
- 4-Methylumbelliferone Targets Revealed by Public Data Analysis and Liver Transcriptome Sequencing.International journal of molecular sciences · 2023Article
- Hepatocyte Smoothened Activity Controls Susceptibility to Insulin Resistance and Nonalcoholic Fatty Liver Disease.Cellular and molecular gastroenterology and hepatology · 2023Article
- Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in industrialized countries and is increasing in prevalence. The pathomechanisms, however, are poorly understood. This study assessed the unexpected role of the Hedgehog pathway in adult liver lipid metabolism. Using transgenic mice with conditional hepatocyte-specific deletion of Smoothened in adult mice, we showed that hepatocellular inhibition of Hedgehog signaling leads to steatosis by altering the abundance of the transcription factors GLI1 and GLI3. This steatotic 'Gli-code' caused the modulation of a complex network of lipogenic transcription factors and enzymes, including SREBP1 and PNPLA3, as demonstrated by microarray analysis and siRNA experiments and could be confirmed in other steatotic mouse models as well as in steatotic human livers. Conversely, activation of the Hedgehog pathway reversed the "Gli-code" and mitigated hepatic steatosis. Collectively, our results reveal that dysfunctions in the Hedgehog pathway play an important role in hepatic steatosis and beyond.
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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.