13 Trainee Award: Postnatal ω-3 polyunsaturated fatty acid supplementation partially resolves adiponectin receptor 2 deficits in skeletal muscle of IUGR-born lambs

Abstract Abstract: Introduction Intrauterine growth restriction (IUGR) causes heightened inflammatory sensitivity in muscle that impairs insulin-stimulated metabolism. This may be facilitated by disruption of adiponectin signaling, which is an insulin sensitizer and is mutually antagonistic with inflammatory signaling. Objective This study evaluated the impact of supplementing anti-inflammatory ω-3 polyunsaturated fatty acids (PUFA) on circulating adiponectin and muscle receptors in IUGR lambs. Methods Maternal heats stress was used to induce unsupplemented (n = 11) and ω-3 PUFA-supplemented (n = 12) IUGR lambs. Controls (n = 12) were born to pair-fed thermoneutral ewes. Blood was collected at 1 and 4 weeks of age to determine adiponectin (ELISA). Semitendinosus muscle was collected at necropsy (day 28) to quantify the adiponectin receptors, CDH13 and AdipoR2 (immunoblot). Results Semitendinosus CDH13 content did not differ among groups. AdipoR2 tended to be 63% less (P=0.09) for unsupplemented IUGR lambs than controls and was intermediate for ω-3 PUFA-supplemented IUGR lambs. Blood plasma adiponectin was 28% greater (P=0.04) for unsupplemented IUGR lambs (3.4±0.2 ng/mL) than for controls (2.7±0.1 ng/mL) and was intermediate for ω-3 PUFA-supplemented IUGR lambs (3.0±0.1 ng/mL), regardless of age. Conclusions These findings demonstrate a potential deficit in adiponectin signaling in IUGR neonatal muscle. Partial resolution of the deficit following ω-3 PUFA supplementation indicate that it was partially due to heightened inflammatory tone. The greater circulating adiponectin, which was also improved by ω-3 PUFA, was paradoxical but may have been a compensatory response to reduced adiponectin sensitivity. Nevertheless, these findings illustrate how anti-inflammatory intervention may improve muscle-centric IUGR metabolic outcomes. (Supported by USDA 2019-67015-29448, 2020-67015-30825)