Portal vein injection of GLP-1 lowers postprandial plasma TG and TRL TG independent of gastric emptying in both hamster and mouse.A-D: Hamsters were fasted for 16 h then received an injection of GLP-1(7-36) (10 μg/kg) or vehicle (PBS) into the portal vein, or an IV infusion of GLP-1 (10 μg/kg) through the jugular line. Hamsters were then fat-loaded with olive oil via oral gavage (200 μl), received IV tyloxapol (2 g/kg), and blood was drawn over a 6 h period via a jugular catheter. E-H: Alternatively, hamsters were pretreated with IP exendin 9-39 10-minutes prior to portal GLP-1 injection. (A/E) Plasma TG, (B/F) plasma TG AUC, (C/G) TRL TG, (D/H) TRL TG AUC. I-L: 16 h fasted hamsters received portal vein injections of GLP-1(7-36) (10 μg/kg) or vehicle (PBS) and then received an intraduodenal infusion of olive oil (200 μl). Pluronic F-127 was administered (2 g/kg; IP) and blood was drawn via retro-orbital bleed over a 6 h period. (I) Plasma TG, (J) plasma TG AUC, (K) TRL TG, (L) TRL TG AUC. M-P: C57BL/6 mice were fasted for 5 h then received a portal vein injection of GLP-1(7-36) (10 μg/kg) or vehicle (PBS), or an extra-portal injection of GLP-1 (10 μg/kg) into the inferior vena cava (IVC). Mice were then fat loaded with an oral gavage of olive oil (200 μl) and received an IP injection of Pluronic F-127 (2 g/kg). Blood was drawn over a 2 h period via the tail vein. (M) Plasma TG, (N) plasma TG AUC, (O) Plasma cholesterol, (P) plasma cholesterol AUC. Data is presented as means ± SEM (A-H: n=5–6/group; I-L: n=6/group; M-P: n=5–6/group). (∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001). ∗; Vehicle vs. Portal GLP-1, ˆ; IV GLP-1 vs. Portal GLP-1, $; IP 9–39 + Portal GLP-1 vs. Portal GLP-1.