Evaluation of the anti-obesity potential of polyphenols through pancreatic lipase inhibition

Obesity is characterized by an accumulation of triglycerides into the adipocytes. Given the importance of lipids from diet on the onset and development of obesity, their absorption, through the activity of the Pancreatic lipase (PL) can be explored for obesity treatment. The available PL inhibitor, Orlistat, is associated with low efficacy and undesirable side effects. Thus, the search and development for new effective and safer agents able to control lipid absorption are urgent for obesity management. Polyphenols are naturally occurring and structurally diverse compounds, with the potential to be explored as anti-obesity agents. This work explores a panel of structurally related polyphenols [flavonoids, chalcones, and 2-styrylchromones (2-SC)] presenting hydroxy and chloro substituents against the PL activity. The influence of polyphenols on PL activity was accessed using a colorimetric microanalysis system based on the enzymatic metabolization of the substrate p-nitrophenyl butyrate. Whenever possible a structure-activity relationship was explored.

Our results showed that from the compounds tested, one chalcone and two 2-SC, presented inhibitory activity against PL. Moreover, the 2-SC structure as well as the presence of a -OH group in the A ring significantly contribute to the observed activity. Further studies were needed to disclose the kinetics of inhibition of these compounds that should be further explored as potential anti-obesity molecules.

The work was supported through the project UIDB/50006/2020 funded by FCT/MCTES through national funds, and from the European Union (FEDER funds through COMPETE POCI-01-0145-FEDER-COMPETE POCI-01-0145-FEDER-029241). Silvia Rocha thanks FCT for her PhD grant (2021.07176.BD).