ArticleMolecules (Basel, Switzerland)2021
Identification of Binding Regions of Bilirubin in the Ligand-Binding Pocket of the Peroxisome Proliferator-Activated Receptor-A (PPARalpha).
Article in Molecules (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 47 citations in OpenAlex.
- Identifying ROCK2 as an intervention target for bilirubin encephalopathy.Fundamental research · 2026Article
- Adipose Tissue Aging and Natural Interventions: Potential Roles of Polyphenols and Polysaccharides.Nutrients · 2026Review
- Leveraging polygenic risk scores to infer causal directions in genotype-by-environment interactions between complex traits.Human genetics · 2026Article
- 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
- Bilirubin Hepatic and Intestinal Transport and Catabolism: Physiology, Pathophysiology, and Benefits.Antioxidants (Basel, Switzerland) · 2025Review
- The physiology of MASLD: molecular pathways between liver and adipose tissues.Clinical science (London, England : 1979) · 2025Review
- Indirect bilirubin is inversely associated with diabetic retinopathy risk and is a potential predictive biomarker.World journal of diabetes · 2025Article
- Bilirubin Targeting WNK1 to Alleviate NLRP3-Mediated Neuroinflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Bilirubin - new insights into an old molecule.Biochemia medica · 2025Review
- Bilirubin metabolism and its application in disease prevention: mechanisms and research advances.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Bilirubin Metabolism Does Not Influence Serum Bile Acid Profiles According to LC-MS: A Human Case-Control Study.International journal of molecular sciences · 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
- The Protective Effect of Bilirubin on MAFLD May Be Mediated by Improving Insulin Re-Sistance and Alleviating Chronic Inflammation.Journal of inflammation research · 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
- Association between bilirubin and biomarkers of metabolic health and oxidative stress in the MARK-AGE cohort.iScience · 2024Article
- Glucocorticoids, their uses, sexual dimorphisms, and diseases: new concepts, mechanisms, and discoveries.Physiological reviews · 2024Review
- Hepatic insulin receptor: new views on the mechanisms of liver disease.Metabolism: clinical and experimental · 2023Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Recent work has shown that bilirubin has a hormonal function by binding to the peroxisome proliferator-activated receptor-α (PPARα), a nuclear receptor that drives the transcription of genes to control adiposity. Our previous in silico work predicted three potential amino acids that bilirubin may interact with by hydrogen bonding in the PPARα ligand-binding domain (LBD), which could be responsible for the ligand-induced function. To further reveal the amino acids that bilirubin interacts with in the PPARα LBD, we harnessed bilirubin's known fluorescent properties when bound to proteins such as albumin. Our work here revealed that bilirubin interacts with threonine 283 (T283) and alanine 333 (A333) for ligand binding. Mutational analysis of T283 and A333 showed significantly reduced bilirubin binding, reductions of 11.4% and 17.0%, respectively. Fenofibrate competitive binding studies for the PPARα LBD showed that bilirubin and fenofibrate possibly interact with different amino acid residues. Furthermore, bilirubin showed no interaction with PPARγ. This is the first study to reveal the amino acids responsible for bilirubin binding in the ligand-binding pocket of PPARα. Our work offers new insight into the mechanistic actions of a well-known molecule, bilirubin, and new fronts into its mechanisms.
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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 Socratic graph.