Abstract 2307 The Loss of Bilirubin's Hormonal Function Drives Metabolic Dysfunction-Associated Steatotic Liver Disease and Adiposity

Obesity, diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD) are increasing globally indicating the urgent need for first-in-class therapeutics. Interestingly, serum bilirubin levels are negatively correlated with these diseases through unknown mechanisms. We have previously generated pegylated bilirubin nanoparticles (PEGBR) and found they have therapeutic potential in preclinical models of diet-induced obesity and MASLD. While bilirubin is primarily recognized for its antioxidant function, our lab identified its hormonal function by binding to and activating the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARa).