Bilirubin Induces the Burning of Fat via the Nuclear Receptor PPARα

Abstract

Deposition fat in adipocytes has become key to understanding how obesity and insulin resistance impact morbidity and mortality. Several studies have shown a decreased amount of body fat in patients with increased plasma bilirubin, which was previously only thought to be a potent antioxidant. Increasing plasma bilirubin levels have been shown to play an integral role in weight loss and are preventive of diabetes as well as cardiovascular events. Our current studies reveal this phenomenon is potentially due to bilirubin binding to the fat burning nuclear receptor peroxisome proliferative‐activated receptor alpha (PPARα) to increase transcriptional activity. We have previously shown that wild‐type and PPARα knockout (KO) mice on a high‐fat diet that were treated with PPARα ligand fenofibrate or bilirubin, had lost the response in the KO mice. Also, the impact of bilirubin on glucose lowering ability as well as weight loss was reduced in the PPARα KO mice. To determine the mechanistic role of the bilirubin‐PPARα axis, we treated adipocytes with biliverdin, a precursor of bilirubin, and known PPARα agonist WY 14,643, and identified by chromatin immunoprecipitation (ChIP) that bilirubin‐PPARα activates the uncoupling protein UCP1 to induce the burning of fat. These all point to the importance and newfound role that bilirubin plays in the burning of fat in adipose to reduce accumulation via binding to PPARα.Support or Funding InformationSource of Funding: This research was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number K01HL125445 (T.D.H.).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.