Hormonal
Bilirubin acts as a direct agonist for the nuclear receptor PPARα, binding to its ligand-binding pocket to upregulate lipid-oxidation genes (CPT1, FGF21) and inhibit lipid accumulation, thereby reducing body fat and blood glucose.
This research identifies bilirubin not just as an antioxidant, but as a functional hormone-like molecule that activates PPARα to burn fat. While you cannot simply 'take' bilirubin safely as a supplement in this context, the findings suggest that individuals with naturally higher bilirubin levels (such as those with Gilbert's Syndrome) may have a metabolic advantage regarding fat loss and glucose control due to this specific receptor activation pathway.
We show that bilirubin can bind directly to PPARα and increase transcriptional activity... Treatment of 3T3-L1 adipocytes with biliverdin suppressed lipid accumulation and upregulated PPARα target genes.
Why this rating
Strong mechanistic evidence in cell lines and mouse models, but lacks direct human clinical trial data for bilirubin supplementation as an intervention.
Source
Bilirubin Binding to PPARα Inhibits Lipid Accumulation
David E. Stec et al. · PLoS ONE · 2016
DOI 10.1371/journal.pone.0153427
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