Bilirubin functioning as a PPARα ligand may explain why mildly elevated plasma bilirubin is protective against MASLD and other metabolic disorders, including obesity and diabetes [58,60,61]; in animal models of MASLD, bilirubin nanoparticle treatment significantly reduced hepatic lipid accumulation through fatty acid β-oxidation activation via PPARα [56]. This evidence concerns the gene PPARA and metabolic disease.