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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #331037
Title: Enteral B-hydroxy-B-methylbutyrate supplementation increases protein synthesis in skeletal muscle of neonatal pigs

Author
item KAO, MICHELLE - Children'S Nutrition Research Center (CNRC)
item COLUMBUS, DANIEL - Children'S Nutrition Research Center (CNRC)
item SURYAWAN, AGUS - Children'S Nutrition Research Center (CNRC)
item STEINHOFF-WAGNER, JULIA - Children'S Nutrition Research Center (CNRC)
item HERNANDEZ-GARCIA, ADRIANA - Children'S Nutrition Research Center (CNRC)
item NGUYEN, HANH - Children'S Nutrition Research Center (CNRC)
item FIOROTTO, MARTA - Children'S Nutrition Research Center (CNRC)
item DAVIS, TERESA - Children'S Nutrition Research Center (CNRC)

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/1/2016
Publication Date: 6/14/2016
Citation: Kao, M., Columbus, D.A., Suryawan, A., Steinhoff-Wagner, J., Hernandez-Garcia, A.D., Nguyen, H.V., Fiorotto, M., Davis, T. 2016. Enteral B-hydroxy-B-methylbutyrate supplementation increases protein synthesis in skeletal muscle of neonatal pigs. American Journal of Physiology - Endocrinology and Metabolism. 310(11):1072-1084.

Interpretive Summary: More than 15% of infants that are born throughout the world are born of a low birth weight. Many remain small to adulthood. To develop new feeding strategies to improve the growth of these infants, scientists at the Children's Nutrition Research Center in Houston, TX investigated the potential for use of beta-hydroxy-beta-methylbutyrate (HMB), a metabolite of the amino acid, leucine, as a supplement in formula. Using a neonatal piglet model, we showed that supplementation with HMB increases the synthesis of protein in muscle by stimulating the intracellular signaling pathways that regulate protein synthesis. HMB also stimulated the proliferation of stem cells in muscle. This work suggests that HMB merits further consideration as a nutritional supplement to enhance muscle growth of low birth weight infants.

Technical Abstract: Many low-birth weight infants are at risk for poor growth due to an inability to achieve adequate protein intake. Administration of the amino acid leucine stimulates protein synthesis in skeletal muscle of neonates. To determine the effects of enteral supplementation of the leucine metabolite B-hydroxy-B-methylbutyrate (HMB) on protein synthesis and the regulation of translation initiation and degradation pathways, overnight-fasted neonatal pigs were studied immediately (F) or fed one of five diets for 24 h: low-protein (LP), high-protein (HP), or LP diet supplemented with 4 (HMB4), 40 (HMB40), or 80 (HMB80) umol HMB kg body wt(-1)/day(-1) Cell replication was assessed from nuclear incorporation of BrdU in the longissimus dorsi (LD) muscle and jejunum crypt cells. Protein synthesis rates in LD, gastrocnemius, rhomboideus, and diaphragm muscles, lung, and brain were greater in HMB80 and HP and in brain were greater in HMB40 compared with LP and F groups. Formation of the eIF4E eIF4G complex and S6K1 and 4E-BP1 phosphorylation in LD, gastrocnemius, and rhomboideus muscles were greater in HMB80 and HP than in LP and F groups. Phosphorylation of eIF2a and eEF2 and expression of SNAT2, LAT1, MuRF1, atrogin-1, and LC3-II were unchanged. Numbers of BrdU-positive myonuclei in the LD were greater in HMB80 and HP than in the LP and F groups; there were no differences in jejunum. The results suggest that enteral supplementation with HMB increases skeletal muscle protein anabolism in neonates by stimulation of protein synthesis and satellite cell proliferation.