| First Author | Stec DE | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 4 | Pages | e0153427 |
| PubMed ID | 27071062 | Mgi Jnum | J:248957 |
| Mgi Id | MGI:6092863 | Doi | 10.1371/journal.pone.0153427 |
| Citation | Stec DE, et al. (2016) Bilirubin Binding to PPARalpha Inhibits Lipid Accumulation. PLoS One 11(4):e0153427 |
| abstractText | Numerous clinical and population studies have demonstrated that increased serum bilirubin levels protect against cardiovascular and metabolic diseases such as obesity and diabetes. Bilirubin is a potent antioxidant, and the beneficial actions of moderate increases in plasma bilirubin have been thought to be due to the antioxidant effects of this bile pigment. In the present study, we found that bilirubin has a new function as a ligand for PPARalpha. We show that bilirubin can bind directly to PPARalpha and increase transcriptional activity. When we compared biliverdin, the precursor to bilirubin, on PPARalpha transcriptional activation to known PPARalpha ligands, WY 14,643 and fenofibrate, it showed that fenofibrate and biliverdin have similar activation properties. Treatment of 3T3-L1 adipocytes with biliverdin suppressed lipid accumulation and upregulated PPARalpha target genes. We treated wild-type and PPARalpha KO mice on a high fat diet with fenofibrate or bilirubin for seven days and found that both signal through PPARalpha dependent mechanisms. Furthermore, the effect of bilirubin on lowering glucose and reducing body fat percentage was blunted in PPARalpha KO mice. These data demonstrate a new function for bilirubin as an agonist of PPARalpha, which mediates the protection from adiposity afforded by moderate increases in bilirubin. |
