SAT-526 - Effect of pregnancy and obesity on extracellular vesicle profiles in ewes

Insulin resistance is a key adaptation of late pregnancy, promoting the diversion of maternal glucose to the fetal unit. Maternal insulin resistance can also become excessive when amplified by obesity. The objective of the study was to test the hypothesis that small extracellular vesicles (sEVs) are involved in the development of maternal insulin resistance during pregnancy and its exacerbation by obesity. sEVs are membrane-bound nanoparticles produced by nearly every tissue in the body and are capable of altering function in recipient cells through the delivery of bioactive cargo. This hypothesis was tested using late-gestating ewes as a model of human pregnancy. Starting 3 months before mating and continuing through pregnancy, ewes were either kept lean by feeding a high-energy diet in amounts that met nutritional requirements or allowed to develop obesity via unrestricted intake. Three groups of ewes were studied: lean, non-pregnant ewes (Lean-NP); lean, pregnant ewes (Lean-PG); and obese, pregnant ewes (Obese-PG) (n = 7 for each group). Metabolic variables were measured between days 108 and 115 of gestation in pregnant ewes and concurrently in Lean-NP ewes. Obese-PG ewes had 1.8-fold greater backfat thickness than Lean-NP and Lean-PG ewes (P < 0.0001). Plasma glucose was unaffected by pregnancy or obesity. Plasma insulin did not differ between Lean-NP and Lean-PG ewes but was 2.4-fold higher in Obese-PG ewes (P < 0.03). Both pregnancy and obesity induced insulin resistance, as shown by reduced glucose disposal in Lean-PG vs. Lean-NP (P < 0.0001), and in Obese-PG vs. Lean-PG (P < 0.05). sEVs were isolated by size exclusion chromatography, and sEV concentration and size were determined by nanoparticle tracking analysis. Plasma sEV concentration was 1.8-fold higher in Lean-PG than Lean-NP ewes (P < 0.05) and numerically higher in Obese-PG than Lean-PG ewes. Obese-PG ewes had smaller sEVs than Lean-NP and Lean-PG ewes (P < 0.02). Additional studies are ongoing to assess the effects of sEVs isolated from each group on insulin-mediated glucose uptake and AKT phosphorylation in myofibers and adipocytes. In conclusion, variation in plasma sEVs may contribute to the insulin resistance of late pregnancy and its amplification by obesity in gestating ewes.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*