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Systemic regulation of bilirubin homeostasis: Potential benefits of hyperbilirubinemia
Author(s) -
Fujiwara Ryoichi,
Haag Mathias,
Schaeffeler Elke,
Nies Anne T.,
Zanger Ulrich M.,
Schwab Matthias
Publication year - 2018
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.29599
Subject(s) - kernicterus , bilirubin , glucuronosyltransferase , unconjugated hyperbilirubinemia , glucuronidation , uridine , medicine , physiology , endocrinology , biochemistry , biology , enzyme , microsome , gene , rna
Neurotoxic bilirubin is the end product of heme catabolism in mammals. Bilirubin is solely conjugated by uridine diphospho‐glucuronosyltransferase 1A1, which is a membrane‐bound enzyme that catalyzes the transfer of glucuronic acid. Due to low function of hepatic and intestinal uridine diphospho‐glucuronosyltransferase 1A1 during the neonatal period, human neonates develop mild to severe physiological hyperbilirubinemia. Accumulation of bilirubin in the brain leads to the onset of irreversible brain damage, termed kernicterus. Breastfeeding is one of the most significant factors that increase the risk of developing kernicterus in infants. Why does this most natural way of feeding increase the risk of brain damage or even death? This question leads to the hypothesis that breast milk–induced hyperbilirubinemia might bring certain benefits that outweigh those risks. While bilirubin is neurotoxic and cytotoxic, this compound is also a potent antioxidant. There are studies showing improved clinical conditions in patients with hyperbilirubinemia. Accumulating evidence also shows that genetic polymorphisms linked to hyperbilirubinemia are beneficial against various diseases. In this review article, we first introduce the production, metabolism, and transport of bilirubin. We then discuss the potential benefits of neonatal and adult hyperbilirubinemia. Finally, epigenetic factors as well as metabolomic information associated with hyperbilirubinemia are described. This review article advances the understanding of the physiological importance of the paradoxical compound bilirubin. (H epatology 2018;67:1609‐1619)