The Role of Vasoactive Intestinal Peptide in Glucagon-like Peptide-2-Mediated Intestinal Lipid Handling

The gut hormone glucagon-like peptide-2 (GLP-2) plays important roles in regulating lipid handling and promoting anti-inflammatory functions in the intestine. During the postprandial state, it increases lipid absorption. During post-absorptive state, it mobilizes pre-formed chylomicrons. GLP-2 acts through vasoactive intestinal peptide (VIP) in reducing inflammation in rat ileum. However, this pathway has not yet been tested for GLP-2’s effects on intestinal lipid handling. Here, in mesenteric lymph duct cannulated rats, we examined whether VIP signaling mediates GLP-2’s effects on postprandial lipid absorption and post-absorptive lipid mobilization in the intestine. We administered a VIP receptor antagonist and analyzed lipid output in response to intraperitoneal GLP-2 or PBS during postprandial and post-absorptive states. VIP receptor antagonism reduced GLP-2 mediated lipid output in the post-absorptive state but had no effect during the postprandial state. These results show that GLP-2 functions differently during postprandial and post-absorptive states and VIP aids in GLP-2-mediated lipid output during the post-absorptive state.