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. 2014 Jan 1;306(1):E91-9.
doi: 10.1152/ajpendo.00500.2013. Epub 2013 Nov 5.

Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of β-hydroxy-β-methylbutyrate

Scott M Wheatley  1 , Samer W El-Kadi, Agus Suryawan, Claire Boutry, Renán A Orellana, Hanh V Nguyen, Steven R Davis, Teresa A Davis
Affiliations

Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of β-hydroxy-β-methylbutyrate

Scott M Wheatley et al. Am J Physiol Endocrinol Metab. .

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 β-hydroxy-β-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 μmol·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 eIF2α 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.

Keywords: amino acid; infant; mtor; protein degradation; protein metabolism.

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Figures

Fig. 1.
Fig. 1.
Fractional rates of protein synthesis in longissimus dorsi (LD), gastrocnemius, soleus, and diaphragm muscles of piglets infused with 0, 20, 100, or 400 μmol·kg−1·h−1 β-hydroxy-β-methylbutyrate (HMB) for 1 h. Values are means ± SE; n = 5–6 per treatment. a,bValues not sharing superscripts differ significantly (P < 0.05).
Fig. 2.
Fig. 2.
Phosphorylation of S6K1 in LD, gastrocnemius, soleus, and diaphragm muscles of piglets infused with 0, 20, 100, or 400 μmol·kg−1·h−1 HMB for 1 h. Values are means ± SE; n = 5–6 per treatment. a,b,cValues not sharing superscripts differ (P < 0.05).
Fig. 3.
Fig. 3.
Phosphorylation of 4E-BP1 in LD, gastrocnemius, soleus, and diaphragm muscles of piglets infused with 0, 20, 100, or 400 μmol·kg−1·h−1 HMB for 1 h. Values are means ± SE; n = 5–6 per treatment. a,b,cValues not sharing superscripts differ (P < 0.05).
Fig. 4.
Fig. 4.
Abundance of eIF4E·eIF4G in LD, gastrocnemius, soleus, and diaphragm muscles of piglets infused with 0, 20, 100, or 400 μmol·kg−1·h−1 HMB for 1 h. Values are means ± SE; n = 5–6 per treatment. a,b,cValues not sharing superscripts differ (P < 0.05).
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