Pancreatic lipase related protein 1 as a potential target in triglyceride breakdown: A molecular docking studies with in vitro appraisal

Abstract

Targeting obesity by altering the absorption of dietary triglycerides by inhibiting the pancreatic lipase is an interesting exploration. We aimed to understand the role of pancreatic lipase related protein 1 (PLRP1) and to explore whether flavonoids could bind to the protein and provide a treatment option for obesity. The selected 50 known plant-derived flavonoids have been tested for pancreatic lipase inhibition activity. The molecular docking analysis were performed to understand the binding interactions of the protein and molecules that have not been previously reported, along with in vitro pancreatic lipase enzyme activity of four flavonoid molecules to support the docking studies. The reported flavonoid molecules were also screened for parameters such as drug-likeness and oral bioavailability. Amongst the 50 tested flavonoid molecules, 13 molecules showing poor GI-absorption in the study. Of note, from the 13 molecules, (−)-epicatechin, cyanidin, petunidin and peonidin were predicted to exhibit the most potent binding with the protein target involving the Glu102, Ser129, ILE 97 and TRP270 residues to be the hotspots towards protein binding. The in vitro results demonstrated that the compound petunidin was potent inhibitor when compared to the control. Also, the kinetics data for all the compounds showed to possess an uncompetitive type of inhibition. Therefore, the findings of this study will be able to deliver useful insights to researchers in designing interesting weight-control drugs. Also, PLRP1 protein could open us a new insight and as an interesting target approach in the triglyceride breakdown for the management of obesity.

Keywords

• Lipid digestion
• Pancreatic lipase
• Obesity
• Triglycerides
• PLRP1
• Molecular docking