The Furan Fatty Acids 11M5 and 11D5 Can Act as Activators of Human Peroxisome Proliferator-Activated Receptor Gamma

Furan fatty acids (FuFA) are a minor class of fatty acids in food that are characterized by a furan ring within the alkyl chain. Furan fatty acids have strong antioxidant properties but their biological functions remain largely elusive. Using molecular docking combined with biomolecular validation, we investigated the regulatory activities of the key furan fatty acids 9M5, 11M5, and 11D5 on human nuclear receptors, including PPARγ, LXR, PXR, FXR, and HNF4α. Using computational methods, 11M5 and 11D5 and to a lesser extend 9M5 were predicted to bind to PPARγ. The activation of both PPARγ1 and PPARγ2 was confirmed in human HEK293T cells and structure-activity experiments revealed that this was dependent on the furan fatty acid backbone. In summary, our data provide novel insights into the biological activities of furan fatty acids in human cells and indicate that activation of peroxisome proliferator-activated receptor gamma underlies their beneficial health effects. These findings establish a clear mechanistic basis, supported by the inactivity of related compounds, and we are confident that future expanded studies will further confirm this mechanism.