Leucine Supplementation Does Not Restore Diminished Skeletal Muscle Satellite Cell Abundance and Myonuclear Accretion When Protein Intake Is Limiting in Neonatal Pigs

• Published in: The Journal of nutrition Vol. 150; no. 1; pp. 22 - 30
• Main Authors: Marko, Rudar, Daniel, A Columbus, Julia, Steinhoff-Wagner, Agus, Suryawan, Hanh, V Nguyen, Ryan, Fleischmann, Teresa, A Davis, Marta, L Fiorotto
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2020; Oxford University Press; American Institute of Nutrition
• Subjects: Abundance; Accretion; amino acid; Amino acids; Animal Feed - analysis; Animal Nutritional Physiological Phenomena; Animals; Animals, Newborn; Babies; Biochemical, Molecular, and Genetic Mechanisms; Bromodeoxyuridine; Catheters; Cells (biology); Child development; Deposition; Diet; Diet - veterinary; Dietary Proteins - administration & dosage; Dietary Supplements; Growth factors; IGF; Insulin; Insulin-like growth factor I; Insulin-like growth factor II; Jugular vein; Leucine; Leucine - administration & dosage; Milk; Morphometry; muscle morphometry; Muscle, Skeletal - metabolism; Muscles; Musculoskeletal system; myoblast; Neonates; Newborn babies; postnatal growth; Protein biosynthesis; Protein synthesis; Proteins; Satellite cells; Satellite Cells, Skeletal Muscle - drug effects; Satellite Cells, Skeletal Muscle - physiology; Skeletal muscle; Swine - physiology; muscle morphometry; amino acid; myoblast; HP; IGF; RPL; CSA; postnatal growth; BW; LD; mTORC1; BCAA; BrdU; RP
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/nxz216

Rapid growth of skeletal muscle in the neonate requires the coordination of protein deposition and myonuclear accretion. During this developmental stage, muscle protein synthesis is highly sensitive to amino acid supply, especially Leu, but we do not know if this is true for satellite cells, the source of muscle fiber myonuclei. We examined whether dietary protein restriction reduces myonuclear accretion in the neonatal pig, and if any reduction in myonuclear accretion is mitigated by restoring Leu intake. Neonatal pigs (1.53 ± 0.2 kg) were fitted with jugular vein and gastric catheters and fed 1 of 3 isoenergetic milk replacers every 4 h for 21 d: high protein [HP; 22.5 g protein/(kg/d); n = 8]; restricted protein [RP; 11.2 g protein/(kg/d);n= 10]; or restricted protein with Leu [RPL; 12.0 g protein/(kg/d);n= 10]. Pigs were administered 5-bromo-2´-deoxyuridine (BrdU; 15 mg/kg) intravenously every 12 h from days 6 to 8. Blood was sampled on days 6 and 21 to measure plasma Leu concentrations. On day 21, pigs were killed and the longissimus dorsi (LD) muscle was collected to measure cell morphometry, satellite cell abundance, myonuclear accretion, and insulin-like growth factor (IGF) system expression. Compared with HP pigs, postprandial plasma Leu concentration in RP pigs was 37% and 47% lower on days 6 and 21, respectively (P < 0.05); Leu supplementation in RPL pigs restored postprandial Leu to HP concentrations. Dietary protein restriction reduced LD myofiber cross-sectional area by 21%, satellite cell abundance by 35%, and BrdU+ myonuclear abundance by 25% (P < 0.05); Leu did not reverse these outcomes. Dietary protein restriction reduced LD muscleIGF2expression by 60%, but notIGF1or IGF1Rexpression (P < 0.05); Leu did not rescueIGF2expression. Satellite cell abundance and myonuclear accretion in neonatal pigs are compromised when dietary protein intake is restricted and are not restored with Leu supplementation.