Continuous Feeding Does Not Blunt Satellite Cell Abundance, Myonuclear Accretion, or Lean Growth in a Neonatal Piglet Model of Prematurity

Objectives Lean growth in preterm neonates is poor and may increase the lifelong risk for adverse health outcomes. Strategies are needed to promote skeletal muscle growth in the postnatal period. Skeletal muscle growth, which accounts for the largest fraction of lean mass accretion, requires the coordinated activation of protein synthesis, satellite cell (SC; muscle stem cell) proliferation, differentiation, and fusion into muscle fibers. The objective of this study was to determine the effect of feeding modality on SC abundance, myonuclear accretion, and lean growth in preterm neonatal pigs. Methods Pigs delivered 10 d preterm by C-section (952 ± 205 g) were fitted with an umbilical artery catheter (later replaced with jugular vein catheter) and an orogastric tube for parenteral and enteral nutrition, respectively. Pigs were assigned to continuous (CONT; n = 14; 7.5 mL/[kg·h]) or intermittent bolus (INT; n = 30; 30 mL/kg every 4 h) feeding for 21 d (210 kcal/kg and 16 g protein/kg per d); pigs were advanced from parenteral to enteral feeding over 6 d. Bromodeoxyuridine (BrdU; 25 mg·kg−1) was administered to pigs every 12 h from days 19 to 20, inclusive, to label proliferating cells. Body composition was measured by DXA on day 21. Satellite cell (Pax7+) abundance, myonuclear accretion, and muscle fiber cross-sectional area (CSA) were quantified in the longissimus dorsi muscle by immunofluorescence. Results Sublaminal Pax7+ SC abundance was similar between CONT and INT groups (60.9 vs. 58.3 ± 6.0 per 1000 fibers). The proportion of sublaminal relative to total Pax7+ SCs was similar between CONT and INT groups (78.8 vs. 78.8 ± 2.2%). The abundance of BrdU + myonuclei, an index of myonuclear accretion, did not differ between CONT and INT groups (26.7 vs. 26.7 ± 3.4 per 1000 fibers). Total myonuclei did not differ between CONT and INT groups (420 vs. 403 ± 16 per 1000 fibers). Muscle fiber CSA did not differ between CONT and INT groups (210 vs. 237 ± 15 µm2). Lean and fat masses were similar between groups. Conclusions Unlike term pigs, CONT feeding does not blunt lean growth in preterm pigs compared to INT feeding. The absence of increased lean growth with INT feeding is consistent with the similar SC abundance, myonuclear accretion, and muscle fiber CSA between feeding modalities. Funding Sources Research was supported by NIH and USDA.