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Postnatal Muscle Growth Is Dependent on Satellite Cell Proliferation Which Demonstrates A Specific Requirement for Dietary Protein
Author(s) -
Fiorotto Marta L.,
Columbus Daniel A.,
SteinhoffWagner Julia,
Suryawan Agus,
Nguyen Hanh V.,
Davis Teresa A.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1244.1
Subject(s) - skeletal muscle , leucine , medicine , endocrinology , biology , muscle mass , muscle fibre , zoology , myofibril , chemistry , biochemistry , amino acid
Extrauterine growth faltering is a serious problem for premature neonates due in large part to insufficient nutrient intake secondary to physiological immaturity and feeding intolerance. Growth of lean mass is especially compromised in these patients due to poor muscle growth. In neonates, short‐term supplementation with leucine of a reduced protein, but energy adequate, feed promoted muscle protein synthesis by stimulating mTORC1 activity similar to feeding a high protein feed. Whether sustained long‐term leucine supplementation of a protein limiting diet can enhance muscle growth is unknown. Five‐d‐old pigs (n = 8–11/diet) were fed by gastric catheter a milk replacement diet with either a high protein (HP) or restricted protein (RP) content or RP supplemented with leucine to the same level as in the HP diet (RPL); all feeds were isocaloric. Pigs were fed every 4 h for 21 d. BrdU (25 mg/(kg.d)) was given as an i.v. bolus every 12 hrs over 3 d from day 6. After 21 d, longissimus dorsi muscle was collected and muscle mass, BrdU+ myonuclei and sublaminal Pax7+ nuclear frequency in muscle cross‐sections were quantified (>1000 fibers/pig). Average fiber cross‐sectional area (CSA) was correlated (r=0.83, P=0.001) with muscle weight and was lower in RP compared to HP pigs (P=0.01), with no improvement in muscle mass with leucine supplementation. Total myonuclear number/fiber also was lower in RP and RPL compared to HP (P=0.01) and was correlated to CSA (r=0.77; P=0.001), with no difference in nuclear domain size (fiber CSA/myonucleus) among groups. There were 40% fewer Pax7+ nuclei in RP and RPL than HP muscles (P=0.001) and their frequency was predictive of myonuclear number/fiber (r=0.79, P=0.001). RP and RPL muscle on average had 30% fewer BrdU+ myonuclei than HP (P=0.003) muscle; the average number of myonuclei per fiber was correlated to the number of BrdU+ nuclei (r=0.76; P=0.001) and the average ratio was similar among groups. The results demonstrate that in the immature muscle fiber hypertrophy is dependent on sustained satellite cell proliferation and myonuclear accretion. This process is highly sensitive to protein intake even when concurrent energy and leucine intakes are optimized for growth. Support or Funding Information Studies were funded by NIH grants: HD072891, AR 46308, AR44474; USDA NIFA 2013‐67015‐20438; USDA/ARS/CSREES 6250‐51000‐55