Metabolites 2025, 15(6), 346; https://doi.org/10.3390/metabo15060346 - 22 May 2025
Abstract
Background/Objectives: Intrauterine growth restriction (IUGR) is associated with enhanced inflammatory activity, poor skeletal muscle glucose metabolism, and pancreatic β cell dysfunction that persist in offspring. We hypothesized that targeting heightened inflammation in IUGR-born neonatal lambs by supplementing anti-inflammatory ω-3 polyunsaturated fatty acids (ω-3
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Background/Objectives: Intrauterine growth restriction (IUGR) is associated with enhanced inflammatory activity, poor skeletal muscle glucose metabolism, and pancreatic β cell dysfunction that persist in offspring. We hypothesized that targeting heightened inflammation in IUGR-born neonatal lambs by supplementing anti-inflammatory ω-3 polyunsaturated fatty acids (ω-3 PUFAs) would improve metabolic outcomes. Methods: Maternal heat stress was used to produce IUGR lambs, which received daily oral boluses of ω-3 PUFA Ca2+ salts or placebo for 30 days. Results: Greater circulating TNFα and semitendinosus IL6R in IUGR lambs were fully resolved by ω-3 PUFA, and impaired glucose-stimulated insulin secretion, muscle glucose oxidation, and hypertension were partially rescued. Impaired glucose oxidation by IUGR muscle coincided with a greater glycogen content that was completely reversed by ω-3 PUFA and greater lactate production that was partially reversed. Ex vivo O2 consumption was increased in IUGR muscle, indicating compensatory lipid oxidation. This too was alleviated by ω-3 PUFA. Conversely, ω-3 PUFA had little effect on IUGR-induced changes in lipid flux and hematology parameters, did not resolve greater muscle TNFR1, and further reduced muscle β2-adrenoceptor content. Conclusions: These findings show that targeting elevated inflammatory activity in IUGR-born lambs in the early neonatal period improved metabolic outcomes, particularly muscle glucose metabolism and β cell function.
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(This article belongs to the Section Nutrition and Metabolism)
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