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  • Title: Dietary glycine supplementation enhances creatine availability in tissues of pigs with intrauterine growth restriction.
    Author: Posey EA, He W, Steele CC, Savell JW, Bazer FW, Wu G.
    Journal: J Anim Sci; 2024 Jan 03; 102():. PubMed ID: 39513322.
    Abstract:
    This study tested the hypothesis that dietary supplementation with glycine (Gly) enhances the synthesis and availability of creatine (Cr) in tissues of pigs with intrauterine growth restriction (IUGR). At weaning (21 d of age), IUGR pigs and litter mates with normal birth weights (NBW) were assigned randomly to 1 of the 2 groups, namely, supplementation with 1% Gly or 1.19% l-alanine (isonitrogenous control) to a corn- and soybean meal-based diet. Blood, kidneys, liver, pancreas, jejunum, longissimus lumborum muscle (LLM), and gastrocnemius muscle (GM) were obtained from the pigs within 1 wk after the feeding trial ended at 188 d of age to determine concentrations of guanidinoacetate (GAA), Cr, creatinine, and phosphocreatine (CrP). The organs were also analyzed for activities and mRNA levels for Cr-synthetic enzymes: l-arginine:glycine amidinotransferase (AGAT; forming GAA from Gly and l-arginine) and guanidinoacetate n-methyltransferase (GAMT; converting GAA and l-methionine into Cr). AGAT activity was present in the kidneys, liver, and pancreas, whereas GAMT activity was found in all the organs analyzed. AGAT and GAMT were most active per gram of tissue in the kidneys and pancreas, respectively. Based on tissue mass, the kidneys had the greatest (P < 0.001) AGAT activity per whole organ, followed by the liver, while skeletal muscle had the greatest (P < 0.001) GAMT activity per whole organ, followed by the liver. Thus, the kidneys played a dominant role in forming GAA, whereas skeletal muscle and liver were the major sites for converting GAA into Cr. Dietary supplementation with 1% Gly enhanced AGAT activity in the kidneys and pancreas but reduced GAMT activity in the pancreas and small intestine, therefore directing GAA to the liver and skeletal muscle for Cr production. IUGR selectively reduced the concentration of Cr in LLM among all the organs studied. Except for the GM that had greater mRNA levels for GAMT in IUGR than in NBW pigs, neither Gly nor IUGR affected mRNA levels for the selected genes in the tissues examined. Collectively, these novel results indicate that dietary Gly intake upregulates the Cr-synthetic pathway in swine. Creatine is essential for growth and energy metabolism in animal tissues but is absent from conventional plant (e.g., corn- and soybean meal)-based diets that contain no animal-sourced ingredients. Thus, livestock (including swine) must synthesize a large amount of creatine from amino acids such as glycine. However, how creatine is formed in growing-finishing pigs remains unknown. Additionally, pigs have the greatest rate of intrauterine growth restriction (IUGR) among livestock species. Because IUGR reduces growth and meat quality, it is imperative to identify interorgan cooperation for creatine synthesis in pigs, particularly those affected by IUGR. Based on the findings of our recently published work that dietary glycine supplementation enhanced the growth performance of IUGR pigs from weaning to market weight, the current research tested the hypothesis that this nutritional strategy also increased the synthesis and availability of creatine in their tissues. Results of the present study indicate that the kidneys are primarily responsible for forming guanidinoacetate from glycine and arginine, whereas skeletal muscle and liver play major roles in converting guanidinoacetate into creatine. Furthermore, dietary supplementation with 1% glycine enhanced the activities of enzymes for creatine synthesis in a tissue-specific manner, as well as concentrations of creatine plus phosphocreatine in the kidneys, liver, pancreas, small intestine, and skeletal muscle of both IUGR and normal-birthweight pigs. Notably, glycine supplementation prevented a decrease in concentrations of creatine in the longissimus lumborum muscle of IUGR pigs. Our findings support the notion that conventional corn- and soybean meal-based diets do not provide sufficient glycine for creatine synthesis in pigs. Dietary glycine supplementation is crucial for their maximal growth and optimal health.
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