Pharmacological inhibition of diacylglycerol acyltransferase-1 and insights into postprandial gut peptide secretion

Figure 1 Diacylglycerol acyltransferase-1 knockout and acute administration of a diacylglycerol acyltransferase-1 inhibitor, PF-04620110 increases postprandial plasma glucagon like peptide-1 levels in mice. Fasted male DGAT1 knockout (-/-), wildtype (+/+) and C57BL/6J mice were administered either vehicle or 10 mg/kg of PF-04620110 by oral gavage (n = 8 per group). Thirty minutes post compound administration mice received a bolus of corn oil (challenge). Blood was collected just prior to bolus (time 0) and at 2 h afterwards for determination of active/total GLP-1 concentrations. (A) Active GLP-1 (pmol/L) and (B) total GLP-1 in DGAT1 -/- and +/+ mice following challenge. (C) Active GLP-1 (pmol/L) and total GLP-1 (D) in C57BL/6J mice treated with vehicle or PF-04620110 following challenge. DGAT1 -/- compared to DGAT1 +/+ and vehicle compared to PF-04620110 treatment at 2 h timepoint (^aP < 0.05, ^bP < 0.01, ^dP < 0.001 Student’s t-test). Values are means ± SEM. DGAT: Diacylglycerol acyltransferase-1; GLP-1: Glucagon like peptide-1.