PSVIII-30 Impaired Glucose-Stimulated Insulin Secretion in Intrauterine Growth-Restricted Neonatal Lambs Is Improved By Daily Supplementation of ω-3 Polyunsaturated Fatty Acid Ca2+ Salts
Authors: White Melanie R , Gibbs Rachel L , Grijalva Pablo Cesar C , Hicks Zena M , Beer Haley N , Most Micah S , Schmidt Ty B B , Peterson Jessica L L , Yates Dustin T 
Published: November 2023

Abstract
Maternofetal heat stress during placental development induces fetal intrauterine growth restriction (IUGR), which in turn reduces birthweight. IUGR-born livestock exhibit deficits in insulin stimulus-secretion coupling and glucose metabolism that contribute to poor growth efficiency. Thus, our objective was to determine whether daily oral supplementation of Ca2+ salts of ω-3 polyunsaturated fatty acids (ω-3 PUFA) to IUGR-born neonatal lambs improves glucose-stimulated insulin secretion and other indicators of metabolic efficiency. Maternal heat stress (40°C, 35% humidity, THI = 85) from d 40 to 95 of gestation was used to induce IUGR. Lambs were weaned at birth and hand-reared on milk replacer. Beginning at birth, lambs received daily oral boluses of 0.5 mL molasses containing 0 or 0.42 g/kg bodyweight of ω-3 PUFA (Virtus Nutrition). All lambs were fitted with femoral catheters at d 24 and a square-wave hyperglycemic clamp study was performed on d 28 to assess basal (i.e., resting) and glucose-stimulated insulin secretion (GSIS). Blood glucose concentrations did not differ among IUGR lambs (n = 8), IUGR+ω-3 lambs (n = 7), and controls (n = 12), but by study design were increased (P &lt; 0.05) 205% from basal during hyperglycemic periods. Basal plasma insulin concentrations did not differ among groups, but basal glucose-to-insulin ratios were greater (P &lt; 0.05) for IUGR+ω-3 lambs than for controls or IUGR lambs. During hyperglycemia, plasma insulin concentrations were 53% less (P &lt; 0.05) for IUGR lambs but only 30% less (P &lt; 0.05) for IUGR+ω-3 lambs compared with controls. Hyperglycemic glucose-to-insulin ratios were greater (P &lt; 0.05) for IUGR lambs (3.24 ± 0.59) compared with controls (1.10 ± 0.29) and were intermediate for IUGR+ω-3 lambs (2.08 ± 0.86). Blood lactate concentrations did not differ among groups or between periods, but blood pH was was greater (P &lt; 0.05) for IUGR (7.448 ± 0.006) and IUGR+ω-3 lambs (7.439 ± 0.003) compared with controls (7.422 ± 0.004). Blood partial pressure of CO2 was less (P &lt; 0.05) for IUGR lambs (43.0 ± 0.3 mmHg) than for controls (46.7 ± 0.9 mmHg) and was intermediate for IUGR+ω-3 lambs (44.0 ± 0.4 mmHg). Blood HCO3 concentrations and O2-bound hemoglobin were greater (P &lt; 0.05) for IUGR and IUGR+ω-3 lambs than for controls. Blood Na+ tended to be less (P = 0.07) and blood K+ was less (P &lt; 0.05) for IUGR and IUGR+ω-3 lambs than for controls. Blood Ca2+ was less (P &lt; 0.05) for IUGR lambs but not for IUGR+ω-3 lambs than for controls. These findings demonstrate that daily oral supplementation of Ca2+ salts of ω-3 PUFA improved deficits in insulin stimulus-secretion coupling and several other metabolic indicators observed in IUGR-born offspring. However, it did not improve all electrolyte concentrations or acid-base balance of the blood.