UC San Diego

Glucagon-like peptide-1 (GLP-1) is an incretin that lowers blood glucose level by enhancing glucose-stimulated insulin secretion (GSIS). GLP-1 receptor agonists (GLP-1-RAs) have been approved to treat type 2 diabetes mellitus and obesity. However, little is mentioned about GLP-1-RA’s effects during pregnancy. Pregnancy induces maternal metabolic adaptation due to the increased fetal energy demands. Studying how pregnancy alters metabolism can help understand pregnancy-related disorders. Our lab found that pregnancy increases the pancreatic α-cell-derived GLP-1 level, which leads to enhanced insulin secretion (Qiao et al., 2022). Since insulin is known to directly affect lipid metabolism, the role of GLP-1 in lipid metabolism, especially placental lipid metabolism, is worth investigating. In this thesis, C57BL/6 mice were injected with semaglutide, a long-acting GLP-1-RA, during their late pregnancy. Tissue samples were collected at E18.5 to study the impact of GLP-1R activation on placental lipid metabolism. Using the oil red O staining, our results showed that semaglutide injection significantly increased placental lipid levels. Surprisingly, semaglutide injection did not alter maternal serum insulin and triglycerides concentrations. There was also no significant change in AKT, AMPK, and mTOR pathways in placentas of semaglutide-treated dams. However, there was a trend of increase in lipoprotein lipase (LPL) mRNA in placentas of semaglutide-treated dams. We speculate that increased LPL expression might increase lipid level in placentas since LPL hydrolyzes circulating triglycerides and facilitates fatty acid uptake by trophoblast cells. However, further studies are needed to confirm this mechanism and to fully understand the role of GLP-1 in lipid metabolism during pregnancy.