title: Enteral β-hydroxy-β-methylbutyrate supplementation increases protein synthesis in skeletal muscle of neonatal pigs.
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 β-hydroxy-β-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) μmol 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 eIF2α 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.
authors.affiliation: United States Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Michelle
authors.initials: M
authors.lastname: Kao
authors.affiliation: United States Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Columbus
authors.affiliation: United States Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Agus
authors.initials: A
authors.lastname: Suryawan
authors.affiliation: United States Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Julia
authors.initials: J
authors.lastname: Steinhoff-Wagner
authors.affiliation: United States Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Adriana
authors.initials: A
authors.lastname: Hernandez-Garcia
authors.affiliation: United States Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Hanh V
authors.initials: HV
authors.lastname: Nguyen
authors.affiliation: United States Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Marta L
authors.initials: ML
authors.lastname: Fiorotto
authors.affiliation: United States Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas tdavis@bcm.edu.
authors.forename: Teresa A
authors.identifier: 0000-0002-4610-9795
authors.initials: TA
authors.lastname: Davis
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004750:Enteral Nutrition; D005260:Female; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects* / Q000502:physiology; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013552:Swine; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014631:Valerates / Q000008:administration & dosage*
chemical_list: D009124:Muscle Proteins; D014631:Valerates; C004961:beta-hydroxyisovaleric acid
keywords: amino acid; infant; protein metabolism; translation initiation