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Title: Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of Beta-hydroxy-Beta-methylbutyrate

Author
item WHEATLEY, SCOTT - Children'S Nutrition Research Center (CNRC)
item EL-KADI, SAMER - Children'S Nutrition Research Center (CNRC)
item SURYAWAN, AGUS - Children'S Nutrition Research Center (CNRC)
item BOUTRY, CLAIRE - Children'S Nutrition Research Center (CNRC)
item ORELLANA, RENAN - Children'S Nutrition Research Center (CNRC)
item NGUYEN, HANH - Children'S Nutrition Research Center (CNRC)
item DAVIS, STEVEN - Abbott Nutrition
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: 11/4/2013
Publication Date: 1/1/2014
Citation: Wheatley, S.M., El-Kadi, S.W., Suryawan, A., Boutry, C., Orellana, R.A., Nguyen, H.V., Davis, S.R., Davis, T.A. 2014. Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of Beta-hydroxy-Beta-methylbutyrate. American Journal of Physiology - Endocrinology and Metabolism. 306(1):E91-99.

Interpretive Summary: One of major challenges facing low-birth-infants is early growth restriction. The objective of this study was to determine the effects of the leucine metabolite called Beta-hydroxy-Beta-methylbutyrate (HMB) on protein synthesis, a major indicator of growth. We used neonatal pig because it is a widely accepted model in human infant growth study. The results show that HMB can increase the protein synthesis of majority of tissues. Our study indicates that HMB can be used improve the growth of neonatal pigs. However, further studies are needed to determine whether our finding can be applicable for improving growth of low-birth-infants.

Technical Abstract: Many low-birth-weight infants experience failure to thrive. The amino acid leucine stimulates protein synthesis in skeletal muscle of the neonate, but less is known about the effects of the leucine metabolite Beta-hydroxy-Beta-methylbutyrate (HMB). To determine the effects of HMB on protein synthesis and the regulation of translation initiation and degradation pathways, overnight-fasted neonatal pigs were infused with HMB at 0, 20, 100, or 400 umol/kg body wt(-1)/h(-1) for 1 h (HMB 0, HMB 20, HMB 100, or HMB 400). Plasma HMB concentrations increased with infusion and were 10, 98, 316, and 1,400 nmol/ml in the HMB 0, HMB 20, HMB 100, and HMB 400 pigs. Protein synthesis rates in the longissimus dorsi (LD), gastrocnemius, soleus, and diaphragm muscles, lung, and spleen were greater in HMB 20 than in HMB 0, and in the LD were greater in HMB 100 than in HMB 0. HMB 400 had no effect on protein synthesis. Eukaryotic initiation factor (eIF)4E per eIF4G complex formation and ribosomal protein S6 kinase-1 and 4E-binding protein-1 phosphorylation increased in LD, gastrocnemius, and soleus muscles with HMB 20 and HMB 100 and in diaphragm with HMB 20. Phosphorylation of eIF2a and elongation factor 2 and expression of system A transporter (SNAT2), system L transporter (LAT1), muscle RING finger 1 protein (MuRF1), muscle atrophy F-box (atrogin-1), and microtubule-associated protein light chain 3 (LC3-II) were unchanged. Results suggest that supplemental HMB enhances protein synthesis in skeletal muscle of neonates by stimulating translation initiation.