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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, S - 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: 1/1/2014
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 neonates is enhanced by administration of beta-hydroxy-beta-methylbutyrate. American Journal of Physiology - Endocrinology and Metabolism. 306:E91-E99.

Interpretive Summary: Low-birth weight babies have lower growth rates compared to normal babies. In order to help low-birth weight babies, we conducted a study using baby pigs (as a model for human babies) to determine the possibility of leucine metabolite called beta-hydroxy-beta-methylbutyrate (HMB) as a supplement that can improve growth. The results show that HMB enhances muscle protein synthesis through the stimulation of the activation of protein synthetic machineries. Our study suggests that in a near future HMB can be used to support growth of low-birth weight babies.

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 ß-hydroxy-ß-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 mu mol·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·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.