Regulation of intestinal lipid and lipoprotein metabolism by the proglucagon-derived peptides glucagon like peptide 1 and glucagon like peptide 2.

PURPOSE OF REVIEW: The intestine is highly efficient at absorbing and packaging dietary lipids onto the structural protein apoB48 for distribution throughout the body. Here, we summarize recent advances into understanding the physiological and pharmacological actions of the proglucagon-derived peptides: glucagon like peptide 1 (GLP-1) and glucagon like peptide 2 (GLP-2) on intestinal lipoprotein secretion.

RECENT FINDINGS: Several recent studies have elucidated mechanisms underlying the paradoxical effects of GLP-1 and GLP-2 on intestinal production of triglyceride-rich lipoproteins (TRLs). Both gut-derived peptides are secreted on an equimolar basis in response to the same nutrient stimulus. Despite neither receptor demonstrating clear localization to enterocytes, a single injection of a GLP-1R agonist rapidly decreases delivery of intestinally packaged fatty acids into the plasma, while conversely GLP-2 receptor (GLP-2R) activation acutely increases TRL concentrations in plasma.

SUMMARY: The regulation of TRL secretion is dependent on the coordination of many processes: fatty acid availability uptake, assembly onto the apoB48 polypeptide backbone, secretion and reuptake, which the hormonal, neural, inflammatory and metabolic milieu can all strongly influence. Understanding of how GLP-1 and GLP-2 receptor agonists control TRL production has clinical importance given that GLP1R agonists were recently demonstrated not only to provide glycemic control but also to prevent major adverse cardiovascular events in patients with T2DM and the success of GLP-2R agonists in treating short bowel disease.