Review: Nutritional regulation of muscle growth in the neonatal swine

Authors: POSEY, E - Children'S Nutrition Research Center (CNRC); DAVIS, TERESA - Children'S Nutrition Research Center (CNRC)

Submitted to: Animal-The International Journal of Animal Biosciences
Publication Type: Review Article
Publication Acceptance Date: 1/6/2023
Publication Date: 4/28/2023
Citation: Posey, E.A., Davis, T.A. 2023. Review: Nutritional regulation of muscle growth in the neonatal swine. Animal-The International Journal of Animal Biosciences. 17(3). Article 100831. https://doi.org/10.1016/j.animal.2023.100831.
DOI: https://doi.org/10.1016/j.animal.2023.100831

Interpretive Summary: Despite advances in medical care, many infants in the U.S. are born prematurely, with low birth weight and increased risk of poor growth and development. Premature birth is linked to lower lean mass and increased lifelong risk for metabolic diseases such as obesity and type 2 diabetes. Understanding the mechanisms that regulate growth and the response to nutrition are needed in order to optimize the nutritional support and develop targeted intervention strategies to promote lean growth. Using the neonatal pig born at term, we have shown that the rapid increase in muscle growth during early neonatal life is driven by an enhanced sensitivity to feeding. This enhanced response to feeding is due to an increased response of both the intracellular insulin signaling pathway and the amino acid signaling pathway that regulate the synthesis of protein in skeletal muscle. These responses decrease with age. However, the capacity of muscle to use nutrients for muscle growth is reduced in the preterm. We showed that the key defect is the reduced ability of skeletal muscle in the preterm to respond to the rise in circulating insulin and amino acids after each meal. We also identified defects in individual components of both the intracellular amino acid signaling pathway and the intracellular insulin signaling pathway that regulate translation initiation and protein synthesis in muscle of the preterm. We further showed that supplementation with the amino acid, leucine, can enhance muscle protein synthesis by stimulating the intracellular amino acid signaling pathway that regulates translation initiation. Thus, targeted nutritional therapies, such as supplementation with leucine, have the potential to promote lean growth and minimize the risk of developing insulin resistance and obesity.

Technical Abstract: Despite advances in the nutritional support of low birth weight and early-weaned piglets, most experience reduced extrauterine growth performance. To further optimize nutritional support and develop targeted intervention strategies, the mechanisms that regulate the anabolic response to nutrition must be fully understood. Knowledge gained in these studies represents a valuable intersection of agriculture and biomedical research, as low birth weight and early-weaned piglets face many of the same morbidities as preterm and low birth weight infants, including extrauterine growth faltering and reduced lean growth. While the reasons for poor growth performance are multifaceted, recent studies have increased our understanding of the role of nutrition in the regulation of skeletal muscle growth in the piglet. The purpose of this review is to summarize the published literature surrounding advances in the current understanding of the anabolic signaling that occurs after a meal and how this response is developmentally regulated in the neonatal pig. It will focus on the regulation of protein synthesis, and especially the upstream and downstream effectors surrounding the master protein kinase, mechanistic target of rapamycin complex 1 (mTORC1) that controls translation initiation. It also will examine the regulatory pathways associated with the postprandial anabolic agents, insulin and specific amino acids, that are upstream of mTORC1 and lead to its activation. Lastly, the integration of upstream signaling cascades by mTORC1 leading to the activation of translation initiation factors that regulate protein synthesis will be discussed. This review concludes that anabolic signaling cascades are stimulated by both insulin and amino acids, especially leucine, through separate pathways upstream of mTORC1, and that these stimulatory pathways result in mTORC1 activation and subsequent activation of downstream effectors that regulate translation initiation Additionally, it is concluded that this anabolic response is unique to the skeletal muscle of the neonate, resulting from increased sensitivity to the rise in both insulin and amino acid after a meal. However, this response is dampened in skeletal muscle of the low birth weight pig, indicative of anabolic resistance. Elucidation of the pathways and regulatory mechanisms surrounding protein synthesis and lean growth allow for the development of potential targeted therapeutics and intervention strategies both in livestock production and neonatal care.