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Review
. 2019 Oct 10;21(11):87.
doi: 10.1007/s11906-019-0994-z.

Bilirubin Safeguards Cardiorenal and Metabolic Diseases: a Protective Role in Health

Terry D Hinds Jr  1 , David E Stec  2
Affiliations
Review

Bilirubin Safeguards Cardiorenal and Metabolic Diseases: a Protective Role in Health

Terry D Hinds Jr et al. Curr Hypertens Rep. .

Abstract

Purpose of review: To discuss recent advances indicating that bilirubin safeguards against cardiorenal and metabolic diseases.

Recent findings: Several investigations from human patient populations and experimental animal models have shown that bilirubin improves cardiorenal and metabolic dysfunction. The latest studies found an entirely new function of bilirubin suggesting that it acts as a hormone signaling molecule capable of activating nuclear receptors for burning fat, which may explain several of its protective actions. This review highlights the current findings (within the last 3 years) regarding cardiorenal and metabolic protective effects of bilirubin and the latest mechanism(s) that may be mediating these effects.

Keywords: Biliverdin reductase; Hypertension; Kidney; Metabolic syndrome; PPARalpha.

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Conflict of interest statement

Conflict of Interest The authors declare no conflicts of interest relevant to this manuscript.

Figures

Fig. 1
Fig. 1
Summary of protective actions of bilirubin. Serum bilirubin levels are regulated by heme oxygenase, biliverdin reductase which is primarily responsible for the generation of bilirubin. Hepatic UDP-glucuronosyltransferase-1 (UGT1A1), organic-anion-transporting polypeptide (OATP), and multidrug resistance proteins (MRP) regulate the levels of serum bilirubin by regulation of the conjugation and transport of bilirubin. Gut bacteria are also responsible for the elimination of bilirubin as well. Bilirubin then acts through multiple pathways, including signaling through peroxisome proliferator-activated receptor-α (PPARα), regulation of inflammation, as well as antioxidant function to exert its cardiorenal and metabolic protection
See this image and copyright information in PMC

References

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    1. Hinds TD Jr, Burns KA, Hosick PA, McBeth L, Nestor-Kalinoski A, Drummond HA, et al. Biliverdin reductase a attenuates hepatic steatosis by inhibition of glycogen synthase kinase (GSK) 3beta phosphorylation of serine 73 of peroxisome proliferator-activated receptor (PPAR) alpha. J Biol Chem. 2016;291(48):25179–91. - PMC - PubMed
    1. Hamoud AR, Weaver L, Stec DE, Hinds TD Jr. Bilirubin in the liver-gut signaling axis. Trends Endocrinol Metab. 2018;29(3): 140–50. - PMC - PubMed

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