ArticleBiomolecules2023
Suppressing Hepatic UGT1A1 Increases Plasma Bilirubin, Lowers Plasma Urobilin, Reorganizes Kinase Signaling Pathways and Lipid Species and Improves Fatty Liver Disease.
Article in Biomolecules, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
26 citing papers in PubMed, 27 citations in OpenAlex.
- Low-dose l-carnitine supplementation attenuates hepatic lipid accumulation in chow-fed mice: Insights from integrated multi-omics analysis.Food chemistry. Molecular sciences · 2026Article
- Longevity-driven hepatic transcriptional programs mediate resilience to diet-induced liver injury in Ames dwarf mice.GeroScience · 2026Article
- GαMetabolites · 2026Article
- Anatomical Atlas of Kinase Responsiveness to Weight Gain: Adipose Depot Reprogramming in Diet-Induced Adiposity.Metabolites · 2026Article
- Kinase signaling in liver disease via clinical-trial-on-a-PamChip: A distinctive methodology for drug mechanisms and personalized medicine.The Journal of biological chemistry · 2026Article
- Transforming Toxicity into Therapy: Exploring Bilirubin's Benefits and Its Molecular Role in Cardiac Health and Disease.Biomolecules · 2026Review
- Microbiome-derived cancer: the catabolism of bilirubin to urobilin in the liver-gut axis and its consequences.Gastroenterology report · 2026Review
- Association Between Adiposity and Low Total Serum Bilirubin Concentration: A Retrospective, Cross-Sectional Study.Health science reports · 2026Article
- Study on the mechanism of action of Kangfuxin liquid in alleviating DSS-induced ulcerative colitis in mice.Frontiers in pharmacology · 2026Article
- Unmasking a neurotoxic duo: a comprehensive overview of fentanyl-xylazine crosstalk in kinase pathways.Frontiers in cellular neuroscience · 2026Article
- Nicotine combined with estrogen activates protein kinase PKCι and TAO, while inhibiting specific MAP kinase pathways in cultured human neurons: an atlas of kinase activities for nicotine use disorder.Frontiers in cellular neuroscience · 2026Article
- Bilirubin Hepatic and Intestinal Transport and Catabolism: Physiology, Pathophysiology, and Benefits.Antioxidants (Basel, Switzerland) · 2025Review
- Article
- The physiology of MASLD: molecular pathways between liver and adipose tissues.Clinical science (London, England : 1979) · 2025Review
- Insulin receptor responsiveness governs TGFβ-induced hepatic stellate cell activation: Insulin resistance instigates liver fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Bilirubin bioconversion to urobilin in the gut-liver-kidney axis: A biomarker for insulin resistance in the Cardiovascular-Kidney-Metabolic (CKM) Syndrome.Metabolism: clinical and experimental · 2025Review
- Heme oxygenase, biliverdin reductase, and bilirubin pathways regulate oxidative stress and insulin resistance: a focus on diabetes and therapeutics.Clinical science (London, England : 1979) · 2025Review
- Urobilin Derived from Bilirubin Bioconversion Binds Albumin and May Interfere with Bilirubin Interacting with Albumin: Implications for Disease Pathology.Biomedicines · 2025Article
- Bilirubin, a hepatoprotective agent that activates SIRT1, PGC-1α, and PPAR-α, while inhibiting NF-κB in rats with metabolic-associated fatty liver disease.Scientific reports · 2024Article
- Glucocorticoid resistance remodels liver lipids and prompts lipogenesis, eicosanoid, and inflammatory pathways.Prostaglandins & other lipid mediators · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Several population studies have observed lower serum bilirubin levels in patients with non-alcoholic fatty liver disease (NAFLD). Yet, treatments to target this metabolic phenotype have not been explored. Therefore, we designed an N-Acetylgalactosamine (GalNAc) labeled RNAi to target the enzyme that clears bilirubin from the blood, the UGT1A1 glucuronyl enzyme (GNUR). In this study, male C57BL/6J mice were fed a high-fat diet (HFD, 60%) for 30 weeks to induce NAFLD and were treated subcutaneously with GNUR or sham (CTRL) once weekly for six weeks while continuing the HFD. The results show that GNUR treatments significantly raised plasma bilirubin levels and reduced plasma levels of the bilirubin catabolized product, urobilin. We show that GNUR decreased liver fat content and ceramide production via lipidomics and lowered fasting blood glucose and insulin levels. We performed extensive kinase activity analyses using our PamGene PamStation kinome technology and found a reorganization of the kinase pathways and a significant decrease in inflammatory mediators with GNUR versus CTRL treatments. These results demonstrate that GNUR increases plasma bilirubin and reduces plasma urobilin, reducing NAFLD and inflammation and improving overall liver health. These data indicate that UGT1A1 antagonism might serve as a treatment for NAFLD and may improve obesity-associated comorbidities.
Indexed as
Identifiers
What OpenQuestion holds
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.