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Heme oxygenase generates carbon monoxide (CO) and biliverdin from the breakdown of heme, and biliverdin is rapidly reduced to bilirubin by the enzyme biliverdin reductase (BVR). Bilirubin has long been thought of as a toxic product that is only relevant to health when blood levels are severely elevated, such as in clinical jaundice. The physiologic functions of bilirubin correlate with the growing body of evidence demonstrating the protective effects of serum bilirubin against cardiovascular and metabolic diseases. Although the correlative evidence suggests a protective effect of serum bilirubin against many diseases, the mechanism by which bilirubin offers protection against cardiovascular and metabolic diseases remains unanswered. We recently discovered a novel function for bilirubin as a signaling molecule capable of activating the peroxisome proliferator-activated receptor\n                    <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                    (PPAR\n                    <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                    ) transcription factor. This review summarizes the new finding of bilirubin as a signaling molecule and proposes several mechanisms by which this novel action of bilirubin may protect against cardiovascular and kidney diseases.\n                  <\/jats:p>","DOI":"10.34067\/kid.0000062022","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T17:55:12Z","timestamp":1648230912000},"page":"945-953","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":17,"title":["Novel Function for Bilirubin as a Metabolic Signaling Molecule: Implications for Kidney Diseases"],"prefix":"10.34067","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8359-4008","authenticated-orcid":false,"given":"David E.","family":"Stec","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, Mississippi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6596-7595","authenticated-orcid":false,"given":"Claudio","family":"Tiribelli","sequence":"additional","affiliation":[{"name":"Fondazione Italiana Fegato-ONLUS, Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olufunto O.","family":"Badmus","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, Mississippi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7599-1529","authenticated-orcid":false,"given":"Terry D.","family":"Hinds","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, Kentucky"},{"name":"Barnstable Brown Diabetes Center, University of Kentucky, Lexington, Kentucky"},{"name":"Markey Cancer Center, University of Kentucky, Lexington, Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,5,26]]},"reference":[{"key":"B1-20250825","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2005.03.010","article-title":"Heme oxygenase and the cardiovascular-renal system","volume":"39","author":"Abraham","year":"2005","journal-title":"Free Radic Biol Med"},{"key":"B2-20250825","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.tem.2015.02.001","article-title":"Biliverdin reductase isozymes in metabolism","volume":"26","author":"O\u2019Brien","year":"2015","journal-title":"Trends Endocrinol Metab"},{"key":"B3-20250825","doi-asserted-by":"crossref","first-page":"9493","DOI":"10.3390\/ijms21249493","article-title":"Natural product heme oxygenase inducers as treatment for nonalcoholic fatty liver 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