ArticleMedical hypotheses2016
Does bilirubin prevent hepatic steatosis through activation of the PPARα nuclear receptor?
Article in Medical hypotheses, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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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
38 citing papers in PubMed, 50 citations in OpenAlex.
- Population Pharmacokinetic Modeling of Diltiazem in Chinese Renal Transplant Recipients.European journal of drug metabolism and pharmacokinetics · 2018Trial
- Hepatic Overexpression of a Novel Soluble Endogenous Transforming Growth Factor β Type II Receptor-Immunoglobulin G1 Fc Fusion Protein (TβRII-SE/Fc) Attenuates Early Stage Metabolic Dysfunction-Associated Steatotic Liver Disease in Rats.ACS pharmacology & translational science · 2026Article
- Associations between serum total bilirubin levels and the prevalence of metabolic syndrome in elderly Chinese males.BMC geriatrics · 2026Article
- A Cross-sectional Data Analysis between Serum Total Bilirubin and Potential Obesity Indices in US Adults.Current molecular medicine · 2026Article
- Circulating urobilinogen augments inflammation and corticosteroid non-response in severe alcohol-induced hepatitis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Bilirubin - new insights into an old molecule.Biochemia medica · 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
- Effects of maternal overnutrition and metabolic challenge in adult life on the histological integrity of the liver and intestinal epithelium in rabbits.Frontiers in nutrition · 2025Article
- The Multifaceted Role of Bilirubin in Liver Disease: A Literature Review.Journal of clinical and translational hepatology · 2024Review
- Review
- The association between bilirubin levels, and the incidence of metabolic syndrome and diabetes mellitus: a systematic review and meta-analysis of cohort studies.Clinical diabetes and endocrinology · 2024Review
- Metabolic-Dysfunction-Associated Steatotic Liver Disease-Its Pathophysiology, Association with Atherosclerosis and Cardiovascular Disease, and Treatments.International journal of molecular sciences · 2023Review
- Hepatic insulin receptor: new views on the mechanisms of liver disease.Metabolism: clinical and experimental · 2023Review
- The physiology of bilirubin: health and disease equilibrium.Trends in molecular medicine · 2023Review
- Bilirubin Nanoparticle Treatment in Obese Mice Inhibits Hepatic Ceramide Production and Remodels Liver Fat Content.Metabolites · 2023Article
- Suppressing Hepatic UGT1A1 Increases Plasma Bilirubin, Lowers Plasma Urobilin, Reorganizes Kinase Signaling Pathways and Lipid Species and Improves Fatty Liver Disease.Biomolecules · 2023Article
- [Nonalcoholic fatty liver disease and bilirubin: correlation, mechanism, and therapeutic perspectives].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023Article
- Bilirubin Levels Are Negatively Correlated with Adiposity in Obese Men and Women, and Its Catabolized Product, Urobilin, Is Positively Associated with Insulin Resistance.Antioxidants (Basel, Switzerland) · 2023Article
- Molecular mechanisms of metabolic associated fatty liver disease (MAFLD): functional analysis of lipid metabolism pathways.Clinical science (London, England : 1979) · 2022Review
- Heme-oxygenase and lipid mediators in obesity and associated cardiometabolic diseases: Therapeutic implications.Pharmacology & therapeutics · 2022Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Several large population studies have demonstrated a negative correlation between serum bilirubin levels and the development of obesity, hepatic steatosis, and cardiovascular disease. Despite the strong correlative data demonstrating the protective role of bilirubin, the mechanism by which bilirubin can protect against these pathologies remains unknown. Bilirubin has long been known as a powerful antioxidant and also has anti-inflammatory actions, each of which may contribute to the protection afforded by increased levels. We have recently described a novel function of bilirubin as a ligand for the peroxisome proliferator-activated receptor-alpha (PPARα), which we show specifically binds to the nuclear receptor. Bilirubin may function as a selective PPAR modulator (SPPARM) to control lipid accumulation and blood glucose. However, it is not known to what degree bilirubin activation of PPARα is responsible for the protection afforded to reduce hepatic steatosis. We hypothesize that bilirubin, acting as a novel SPPARM, increases hepatic fatty acid metabolism through a PPARα-dependent mechanism which reduces hepatic lipid accumulation and protects against hepatic steatosis and non-alcoholic fatty liver disease (NAFLD).
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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.